H

OH
OH
metabolites

Review
Degradation of Xenobiotic Pollutants: An Environmentally
Sustainable Approach
Rashi Miglani 1 , Nagma Parveen 1 , Ankit Kumar 2 , Mohd. Arif Ansari 3 , Soumya Khanna 4 , Gaurav Rawat 1 ,
Amrita Kumari Panda 5 , Satpal Singh Bisht 1 , Jyoti Upadhyay 6, * and Mohd Nazam Ansari 7, *

1 Department of Zoology, D.S.B Campus, Kumaun University, Nainital 263002, Uttarakhand, India
2 Department of Pharmaceutical Sciences, Sir J. C Bose Technical Campus, Bhimtal,
Nainital 263136, Uttarakhand, India
3 Department of Forestry and Environmental Science, D.S.B Campus, Kumaun University,
Nainital 263002, Uttarakhand, India
4 Department of Anatomy, Banaras Hindu University, Varanasi 221005, Uttar Pradesh, India
5 Department of Biotechnology, Sant Gahira Guru University, Ambikapur 497001, Chhattisgarh, India
6 Department of Pharmaceutical Sciences, School of Health Sciences and Technology, University of Petroleum
and Energy Studies, Energy Acre Campus Bidholi, Dehradun 248007, Uttarakhand, India
7 Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University,
Al-Kharj 11942, Saudi Arabia
* Correspondence: jupadhyay@ddn.upes.ac.in (J.U.); nazam.ansari@gmail.com (M.N.A.)

Abstract: The ability of microorganisms to detoxify xenobiotic compounds allows them to thrive in a
toxic environment using carbon, phosphorus, sulfur, and nitrogen from the available sources. Bio-
transformation is the most effective and useful metabolic process to degrade xenobiotic compounds.
Microorganisms have an exceptional ability due to particular genes, enzymes, and degradative
Citation: Miglani, R.; Parveen, N.;
mechanisms. Microorganisms such as bacteria and fungi have unique properties that enable them
Kumar, A.; Ansari, M.A.; Khanna, S.; to partially or completely metabolize the xenobiotic substances in various ecosystems.There are
Rawat, G.; Panda, A.K.; Bisht, S.S.; many cutting-edge approaches available to understand the molecular mechanism of degradative
Upadhyay, J.; Ansari, M.N. processes and pathways to decontaminate or change the core structure of xenobiotics in nature.
Degradation of Xenobiotic Pollutants: These methods examine microorganisms, their metabolic machinery, novel proteins, and catabolic
An Environmentally Sustainable genes. This article addresses recent advances and current trends to characterize the catabolic genes,
Approach. Metabolites 2022, 12, 818. enzymes and the techniques involved in combating the threat of xenobiotic compounds using an
https://doi.org/10.3390/ eco-friendly approach.
metabo12090818

Academic Editor: Thusitha W. Keywords: xenobiotics; enzymes; microorganisms; metagenomics; sustainability

Rupasinghe

Received: 21 July 2022

Accepted: 29 August 2022
1. Introduction
Published: 31 August 2022
In the industrial revolution and urbanization era, the global environment’s poisoning
Publisher’s Note: MDPI stays neutral
by a complex mixture of xenobiotics has become a major environmental threat world-
with regard to jurisdictional claims in
wide [1,2]. Xenobiotic contaminants such as azodyes, phenolics, polycyclic aromatic hydro-
published maps and institutional affil-
carbons (PAHs), halogenated compounds, personal care products (PCPs), pharmaceuticals’
iations.
active compounds (PhACs), pesticides, nitroaromatic compounds, triazines, and chlori-
nated compounds adversely affect the environment by their long-term persistence and slow
or no biodegradation in the ecosystems [3–5]. Once xenobiotics are discharged into the
Copyright: © 2022 by the authors.
environment, they enter the food chain, causing harmful impacts at each trophic level and
Licensee MDPI, Basel, Switzerland. adversely affecting human and animal health. In 1960s, the discovery of DDT (dichloro-
This article is an open access article diphenyl-trichloroethane), and methyl mercury residues in fish and wildlife sparked public
distributed under the terms and interest in the bioaccumulation of xenobiotic chemicals [6–10]. In addition, these pollutants
conditions of the Creative Commons have teratogenic, carcinogenic, mutagenic, and toxic effects on all organisms. Therefore,
Attribution (CC BY) license (https:// removing toxic undegradable xenobiotics from the environment is necessary [11,12]. These
creativecommons.org/licenses/by/ xenobiotic compounds have been degraded by physical and chemical methods such as
4.0/). coagulation, filtration, adsorption, chemical precipitation, electrolysis, and ozonation.

Metabolites 2022, 12, 818. https://doi.org/10.3390/metabo12090818 https://www.mdpi.com/journal/metabolites

Metabolites 2022, 12, 818 2 of 27

However, it is not always cost-effective; lack of space, complicated procedures, stringent

regulatory requirements imposed on decontamination by various countries, public dissatis-
faction, waste disposal issues, and toxic by-products turn more hazardous than the parent
compounds [2,13,14].
Over the past few decades, microbial-assisted degradation (bioremediation) of xeno-
biotic pollutants has evolved into the most effective, environment-friendly, cost-effective
method for removing these noxious contaminants. Bioremediation is a method that in-
volves the destruction, eradication, immobilization, or detoxification of a wide range of
chemical waste and other harmful chemicals from the environment by an inclusive action
of microorganisms. Bioremediation-related technologies include phytoremediation, rhi-
zofilteration, bioaugmentation, biostimulation, landfarming, bioreactors, and composting.
It is now gaining popularity; this method takes advantage of microorganisms’ metabolic
capabilities to eliminate contaminants, making them the most appropriate and promis-
ing. Persistent organic pollutants (POPs) cleanup with microbial enzymes is eco-friendly,
cost-effective, and inventive [15,16].
Various laws and rules have been formulated to address the problems of xenobiotics,
and many patents have been adopted and are in use in the EU and around the world, with
an increased focus on reducing xenobiotics from the environment in a way that is economi-
cally, environmentally, and socially acceptable and viable with reduced accumulation or
generating other toxic components in nature [17]. Furthermore, patents are an accurate
indicator of inventive activity and their implementation in the analysis of xenobiotics and
other harmful products could help scientists, stakeholders (technologists, business leaders,
attorneys), policymakers, and researchers to gain access to technology updates, develop
new processes and products, design future research strategies, and make critical decisions
for developing R&D investment plans for more significant economic and environmental
growth [18]. This review aims to convey up-to-date knowledge on recently identified
catabolic genes for xenobiotic pollutants using various omics technologies. In addition,
this review gives a concise note on the role of microbial enzymes in the detoxification of
xenobiotics and also highlights various patents filed for the transformation of xenobiotics
from various environments.

2. Xenobiotic Pollution and Its Impact on the Environment

Xenobiotic pollution of the environment is a global concern caused by anthropogenic
activities such as urbanization and population expansion. The enormous amounts of
harmful compounds released into the environment result in widespread ecosystem contam-
ination. Prominent substances such as polycyclic aromatic hydrocarbons (PAHs), heavy
metal ions, pesticides, fertilizers, and oil derivatives are found in soil, sediment, and
water [4].
During the Industrial Revolution, scientific and technological advances became a
source of people’s over-exploitation of resources, which destroyed various ecosystems [19].
The irrational use of human, veterinary drugs and pharmaceutical waste is another well-
known contributor to environmental contamination. Compared to other chemical com-
pounds, medicines potentially impact aquatic flora and fauna. However, pharmaceuticals
are believed to cause only a minimal risk of acute environmental toxicity. The scenario may
differ for chronic effects; nevertheless, there is a substantial dearth of evidence about chronic
effects and their toxicity. Furthermore, there is little or no evidence of multi-generational life
cycle consequences, even though many aquatic creatures are exposed to toxicity throughout
their life [20].
Major xenobiotic compounds have hazardous effects on the environment, plants,
animals, and humans (Table 1; Figure 1).
Metabolites 2022, 12, x FOR PEER REVIEW 3 of 30

Metabolites 2022, 12, 818 3 of 27

Table 1. Major xenobiotic compounds and their effects.

Xenobiotic Compounds. Possible Effects Consequences Observed References

Polychlorinated Table 1. Major xenobiotic compoundsWide range
and their of neural abnormalities i.e.,
effects.
biphenyls (PCBs) Pediatric neurological disorder Abnormal reflexes and neural tissue [21,22]
Xenobiotic Compounds.
PCB-156,180,194 Possible Effects Consequences
damage Observed References
Halocarbonsbiphenyls (PCBs) Wide range of neural
Polychlorinated Global warming Pediatric neurological
and climate
CFCs, H(C)FCs, CH3CCl3,
PCB-156,180,194 Loss of biodiversity andi.e.,
abnormalities Abnormal
habitat destruction [21,22]
[23,24]
change disorder reflexes and neural tissue damage
CCl4, CFC-12 HFC-134a
Halocarbons Accumulation of PVC and PP AlterationLossin the food chain and
andhabitat
food webs,
Global warming and climate of biodiversity
Synthetic
CFCs, H(C)FCs,polymers
CH3 CCl3, CCl4, CFC-12 [25,26]
[23,24]
products change aquatic anddestruction
soil pollution
HFC-134a
Pharmaceuticals
Alteration in the food chain and
Analgesics, Antibiotics, Accumulation of PVC Adverse
and PP effect on the reproductive potential
Synthetic polymers food webs, aquatic and soil [25,26]
products
Antiepileptic, Antiseptics, Cellular and tissue damage of aquatic, terrestrialpollution
and arboreal animals, [27]
Beta-blocker, estrogenic
Pharmaceuticals LethalAdverse
effect oneffect
scavengers
on the
drugs
Analgesics, Antibiotics, Antiepileptic, reproductive potential of aquatic,
Cellular and tissue damage [27]
Antiseptics,
Polycyclic Beta-blocker,
Aromatic estrogenic terrestrial and
Genotoxicity, arboreal stress,
oxidative animals,
drugs Aquatic and avian ecosystem Lethal effect on scavengers
hydrocarbons immunosuppression and hormonal [28]
toxicity Genotoxicity, oxidative stress,
PAHs
Polycyclic Aromatic hydrocarbons Aquatic and avian ecosystem disorders
immunosuppression and [28]
PolybromonatedPAHs toxicity
Adverse effects on hormone T3 Disorders of the hormonal
thyroiddisorders
gland and related
biphenyls [29]
Polybromonated biphenyls and T4 secretion
Adverse effects on hormone Disordershormones
of the thyroid gland
PBBs PBBs T3 and T4 secretion and related hormones
[29]
Pesticides
Pesticides Biomagnification and
Biomagnification and Endocrinal anomalies,
Endocrinal embryonic
anomalies, embryonic cell
Herbicides, Fungicides [30]
[30]
Herbicides, Fungicides and Insecticides
bioaccumulationbioaccumulation
hazards hazards cell toxicity
toxicity in aquatic
in aquatic animals
animals
and Insecticides
Nephrotoxicity, hepatotoxicity, Metabolic disorder, cellular and
Heavy metals Nephrotoxicity, hepatotoxicity,
contamination of water tables,
Metabolic organ damagecellular
disorder, and a variety of
and organ [31]
Heavy metals contamination of water tables,
aquatic water carcinogenic effects [31]
damage and a variety of carcinogenic effects
aquatic water

Figure1.1.Hazardous
Figure Hazardous effects
effects are
arecaused
causedbybydirect
director
orindirect
indirectexposure
exposureof
ofxenobiotic
xenobioticcompounds
compounds on on
the environment, plants, animals and human health. Xenobiotics impose ecotoxicological effects on
the environment, plants, animals and human health. Xenobiotics impose ecotoxicological effects
soil organisms, reduce microbial activity, and change the soil’s physico-chemical properties. Releas-
on soil organisms, reduce microbial activity, and change the soil’s physico-chemical properties.
ing xenobiotic compounds to aquatic systems (fresh and marine water) causes eutrophication and
Releasing xenobiotic
severe threats compounds
to faunal diversity,toincluding
aquatic systems (freshand
deformities anddevelopmental
marine water) disorders.
causes eutrophication
In addition,
and severe threats to faunal diversity, including deformities and developmental disorders. In addition,
continuous exposure to xenobiotics adversely affects the immune, reproductive and nervous systems
and sometimes causes various cancers.
Metabolites 2022, 12, 818 4 of 27

2.1. Impact of Xenobiotics on Soil

Xenobiotics such as dioxins, 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT),
polychlorinated biphenyls (PCBs), chlordane, polycyclic aromatic hydrocarbons (PAHs),
and nitroaromatics are the primary threat to the soil ecosystems of developed nations.
However, there are reports that a few other pollutants such as benzene, nitrobenzene,
toluene, xylene, aniline, ethylbenzene, trinitrotoluene/dibenzofurans, and chlorinated
solvents could be xenobiotic, especially in the soil ecosystem [32]. Cosmetics and personal
care products also contribute as xenobiotic pollutants, especially parabens in soil and
air [33] and azodyes in soil, due to one or more aromatic rings and azo bonds [34].
Anthropogenic activities that stimulate these chemical compounds in soil include
industrial activities, fuel combustion, military movement, use of pesticides, fertilizers,
and soil modifications in high-production agricultural practices that cause detrimental
effects [35,36]. Chemical characteristics of xenobiotics and site conditions influence their
bioavailability, and distribution in soil, with soil organic matter(SOM) playing an important
role [37]. Pesticides (herbicides, insecticides, fungicides, algaecides, bactericides, etc.) are
chemicals used for crop protection and management and are the most widely used toxins
in the environment over the last century. Millions of tonnes of pesticides are produced and
spread each year around the world [38]. Environmental factors such as temperature, soil
pH, and moisture significantly impact the behavior of persistent organic pollutants (POPs)
in the soil. One possible strategy is binding xenobiotic compounds to soil organic matter
(SOM). Many xenobiotics and their degraded products resemble humic precursors and are
frequently used in humification. It has been suggested that this naturally existing process
is used to neutralize environmental contaminants found in soil. Inorganic minerals interact
well with xenobiotics and play a crucial role in xenobiotic transformation [39].

2.2. Impact of Xenobiotics on Water

The diffusive and point contributions of anthropogenic activities such as urban indus-
trial production, transportation, building construction, and housing pollute surface and
groundwater in urban areas. The presence of chemical substances and indicators of human
activity in urban water systems has been the subject of numerous kinds of research [40]. In
sewage treatment plants, some common xenobiotics sensors must be treated with municipal
wastewater before being discharged into aquatic systems. Several trace metals, xenobiotic
substances, and synthetic organic chemicals, such as PAHs, phthalates, and pesticides, are
also noticed in different water bodies [41]. Xenobiotic substances can enter water bodies
through different sources. These include (a) airborne particulate deposition; (b) surface
water running from roads and land surfaces; (c) continuous inputs from commercial and
sewage effluents, as well as fossil fuel products; (d) solid waste burning [42]. Xenobiotics
substances also reach the water table through the leaching process, which affects the bio-
logical integrity of aquatic ecosystems [20]. The presence of xenobiotic pollutants induces
oxidative stress among aquatic organisms. A recent study by Ibor et al. [43] observed a
significant increase in oxidative stress response in the fish fauna of an artificial Eleyele
lake, Nigeria.
A study reported that xenobiotic compounds alter the homeostasis in fishes and cause
oxidative stress by producing large numbers of reactive oxygen species and suppressing
the antioxidant system [44].

2.3. Impact of Xenobiotics on Plants

Xenobiotics affect the plant’s physiological and morphological characteristics in many
ways; for example, particulate matter from the automobile sector changes the photosyn-
thetic pigments, protein, cysteine contents, leaf area, and the foliar surface of plants [45].
The extensive range of xenobiotics with diverse structures and designs causes changes in
gene expression, regulation, and signal transduction in the higher plants. Xenobiotics, such
as phytohormone analogs, have intrinsic interactions with plant hormone receptors and
signaling pathways [46]. Metals that are needed for plant growth, such as Cu, Zn, Fe and
Metabolites 2022, 12, 818 5 of 27

Mo, have deleterious effects at high concentrations, but metals that are not essential for
plant growth, such as Pb, Cd, Hg and As, have adverse effects even at low concentrations
in plant growth [47]. Xenobiotics induce DNA damage in the case of plants due to the
production of reactive oxygen species and oxidative stress. The signaling pathways get
deregulated due to xenobiotic toxicity in plants by influencing various signaling receptors
such as G-Protein coupled receptor and receptor tyrosine kinase [48].

2.4. Impact of Xenobiotics on Marine Life

Xenobiotics negatively impact several metabolic processes of marine animals, partic-
ularly in developing fish embryos, causing morphological and functional abnormalities,
retarded growth leading to death. Altered body shape, body abnormalities, hatching de-
lays, and death have also been recorded in fishes [49]. Dyes and paints are also considered
xenobiotics because they restrict sunlight penetration and inhibit gas exchange even if
they are present in the traces [50]. Pesticides and herbicides are significant sources of
xenobiotic pollution in marine life. Chemicals, including organophosphorus, nitrophenols,
morpholine, synthetic pyrethroids, and carbamates, are often used in agricultural and
daily life; later on, these substances enter various water bodies, including the sea and
ocean. Insecticide such as β-Cypermethrin is a severe threat to the life of marine life and
invertebrates [51].

2.5. Impact of Xenobiotics on Terrestrial Animals

Xenobiotic exposure is also possible due to application or inoculation of pharmacologic
drugs or other chemicals as part of a typical conditioning or experimental operation. The
consumption pattern and disposition of xenobiotics determine their toxicity. In addition,
the mechanical and chemical properties also play a vital role in determining the toxicity
of these xenobiotics’ compounds [52]. The xenobiotics and their metabolites may induce
physiological changes in animals by altering immunological functions, cardiovascular
indices, or organ systems. For example, ivermectin, a popular anthelmintic and acaricide,
is harmful to some dog breeds and mouse strains due to a lack of p-glycoprotein [53].
Compared to controls, pazufloxacin and meloxicam cause oxidative damage in rabbits,
including decreased glutathione content and considerable lipid peroxidation [54].

2.6. Impact of Xenobiotics on Human Health

Xenobiotics pollute the environment, so their assimilation by living species has in-
creased dramatically in recent decades. Introducing these substances into ecosystems
may increase allergic reactions, organism mortality, genetic alterations, immune system
lowering, metabolic disorders, and disruptions in natural ecosystem processes [55]. Hu-
mans are exposed to a wide range of xenobiotics, such as medications and non-essential
exogenous substances, throughout their lives by ingesting, breathing, dermal contact, or
any other intravenous route of exposure that may represent a risk to human health [56].
Xenobiotics may alter the human gut microbiome leading to dysbiosis, which is indirectly
linked to various undesirable health outcomes. The continuing biotransformation process
consistently seeks to balance the metabolic activation of xenobiotics to the detoxification
of their mutagenic metabolites, as it evolved to neutralize and remove body-invading
agents. When this balance is disrupted, chronic diseases and DNA damage in the human
body can occur. The toxicity of xenobiotics varies significantly between individuals. These
oscillations are caused by the organism’s enhanced sensitivity and intraspecific variability.
A large spectrum of substances is utterly foreign to the human body. These chemicals
have harmful and irritating effects on various human organs and systems directly and
indirectly [57].

3. Omics Approaches to Combat Xenobiotic Pollution

Human activities regularly emit xenobiotics into the environment, causing pollution
and harming human and natural ecosystems. However, certain xenobiotic-degrading
 indirectly [57].

3. Omics Approaches to Combat Xenobiotic Pollution

Human activities regularly emit xenobiotics into the environment, causing pollution
Metabolites 2022, 12, 818 6 of 27
and harming human and natural ecosystems. However, certain xenobiotic-degrading bac-
teria and fungi have been identified. Most of the xenobiotic-degrading bacterial strains
rely only on xenobiotics for their carbon source and energy, making them great models
bacteria and fungi have been identified. Most of the xenobiotic-degrading bacterial strains
for studying bacterial adaptability and evolution in the environment (Figure 2) [58]. Ini-
rely only on xenobiotics for their carbon source and energy, making them great models for
tially, bacterial strains with metabolic properties were isolated and cultured to degrade
studying bacterial adaptability and evolution in the environment (Figure 2) [58]. Initially,
pollutants. However,
bacterial strains with very few microbes
metabolic properties are
werecultivable
isolated and with xenobiotic
cultured degradative
to degrade pollu- po-
tential;
tants.few of them
However, veryhave
fewbeen isolated
microbes and characterized
are cultivable in thedegradative
with xenobiotic recent past with incom-
potential;
parable
few of biodegradation ability and
them have been isolated suchcharacterized
as Alcaligenes [59],
in the Pseudomonas
recent [60], Enterobacter,
past with incomparable
Achromobacter, ability such as Alcaligenes
biodegradationHyphomicrobiaceae, [59], Pseudomonas
Microbacterium [61], [60], Enterobacter,
Micrococcus andAchromobacter,
Rhodococcus [62],
Hyphomicrobiaceae, Microbacterium [61], Micrococcus and Rhodococcus [62],
Aeromonas [63], Sphingobium [64], Aspergillus and Purpureocillium [65], Penicillium Aeromonas [63], and
Sphingobium [64], Aspergillus and Purpureocillium [65], Penicillium and Trichoderma [66],
Trichoderma [66], Rhodotorulaand Candida [67] etc. Hence, new culture-independent ap-
Rhodotorula and Candida [67] etc. Hence, new culture-independent approaches such as
proaches such as metagenomics are gaining momentum to identify non-cultivable mi-
metagenomics are gaining momentum to identify non-cultivable microbes with xenobiotic
crobes with xenobiotic
degradation degradation
potential [68,69]. potential
Few relevant [68,69]. degrading
xenobiotic Few relevant xenobiotic degrading
microorganisms were
microorganisms were identified with
identified with culture-independent culture-independent
approaches, approaches,
such as Sphingopyxis, such as Sphin-
Afipia, Oligotropha,
gopyxis, Afipia, Oligotropha,
Rhodopseudomonas, Rhodopseudomonas,
Mesorhizobium, Mesorhizobium,
and Stenotrophomonas [70]. Theand Stenotrophomonas
dominance of Thalas- [70].
The dominance
solituus of Thalassolituus
and Oleispira have also and
beenOleispira
identifiedhave alsooil-degrading
as vital been identified as vital
bacteria oil-degrad-
through
ingmetagenomics and the
bacteria through metatranscriptomic
metagenomics and theapproach [71].
metatranscriptomic approach [71].

Figure 2. Distinct features of multi-omics technologies in the transformation of xenobiotic

Figure 2. Distinct features of multi-omics technologies in the transformation of xenobiotic compounds.
compounds. Genomics and metagenomics identify detoxifying enzymes from the whole genome or
Genomics and metagenomics identify detoxifying enzymes from the whole genome or metagenome
metagenome sequencing data. RNA seq or transcriptomics data indicate up- and down-regulated
sequencing data. RNA seq or transcriptomics data indicate up- and down-regulated genes in response
genes in response to xenobiotic exposure. Proteomics techniques help to compare the changes in
to xenobiotic exposure. Proteomics techniques help to compare the changes in protein profile in the
protein profile in the presence and absence of toxic compounds.
presence and absence of toxic compounds.

3.1.3.1.
Genomics
Genomicsand
andMetagenomics
Metagenomics
Genome sequencing of uncultured microorganisms helps to find new genes associated
with the microbe and gives details of the degradation potential of these microbial commu-
nities. Genomics determines the genetic information and metagenomics determines the
genetic sequences of a community of an organism in total. Internal transcribed spacer (ITS)
regions distinguish fungal DNA from other organisms in the ribosomal genes. Plants or
bacteria do not share these regions. Thus, ITS amplicon sequencing helps identify fungal
species able to degrade xenobiotic compounds [72]. Functional metagenomics studies
Metabolites 2022, 12, 818 7 of 27

demonstrated that Burkholderia, Bradyrhizobium, Koribacter and Acidomicrobium were the

most abundant genera in soil contaminated with pesticides [73]. This study also reported
the abundance of phosphodiesterase encoding genes that plays a vital role in organophos-
phorus degradation. Whole-genome sequencing studies of atrazine-degrading Pseudomonas
sp. Strain ADPe, Variovorax sp. Strain 38R, Arthrobacter sp. Strain TES, Chelatobacter sp.
Strain SR38 [74] using Illumina HiSeq 3000 platform unravel the genetic changes in the
strains during environmental challenges.
The Gordonia sp. 1D genome analysis revealed the existence of two alkane hydroxylase
gene clusters, dibenzothiophene cleavage genes, and intermediates in the metabolism
of salicylate and gentisate-naphthalene. In hot climates, the highly effective thermotol-
erant strain Gordonia sp. 1D can be employed to remediate oil-contaminated soils [75].
Complete genome sequence data for several significant microbial strains, including She-
wanella oneidensis MR-1, Pseudomonas aeruginosa KT2440, Deinococcus indicus R1, and
Dehalococcoides mccartyi WBC-2, have already been provided, which is crucial for efficient
bioremediation (http://www.tigr.org, accessed on 20 February 2022).
The metagenomic approach is called ecogenomics, community, or environmental
genomics [68]. Metagenomic approaches can link microbial identity, functional diver-
sity, and the role of essential genes, for which metagenomic libraries are constructed.
Although sequence-driven and function-driven approaches are used for diversity screen-
ing, novel gene identification and functions are being studied in a new approach called
function-driven metagenomics. Low recovery of active clones is the main limitation of this
approach [76–78].

3.2. Transcriptomics and Metatranscriptomics

A subset of genes transcribed to RNA is referred as transcriptome and links the
genome, the proteome, and the cellular phenotypes. The mRNA expression level, which is
upregulated or downregulated in an organism, can be determined using RNA sequencing
and DNA microarrays [79,80]. The mRNA expression level changes with the environ-
mental conditions which the organisms inhabit; the high cost, tremendous efforts, and a
smaller number of genes to be analyzed limits the use of DNA microarray [79]. Also, when
interpreting the microarray data statistically, there are chances of false results [81]. RNA
sequencing has the edge on DNA microarrays due to a more comprehensive quantitative
range of expression [82]. Hence, many studies are now relying upon this particular ap-
proach. The transcriptomic study of a DDT-resistant Trichoderma hamatum FBL 587 showed
upregulation of around 1706 genes involved in DDT degradation and upregulation of
many DDT-metabolizing enzymes such as FAD-dependent monooxygenases, epoxide
hydrolases, glycosyl- and glutathione-transferases [83]. Lima-Morales et al. [84] investi-
gated the catabolic gene diversity of BTEX-contaminated soil under continuous long-term
pollutant stress to identify the occurrence of important genes for catabolic pathways. The
RNA-seq and coexpression network analysis approach was used to reveal the metabolism
of hexabromocyclododecane degradation in Rhodopseudomonas palustris [85]. Lima-Morales
et al. further confirmed the over-expression of hexabromocyclododecane degradation
enzymes such as glutathione-S-transferase, haloacid dehalogenases, cytochrome p450,
dioxygenases and transcriptional regulator LysR by qRT-PCR. The mechanism of break-
down of organophosphorous pesticide phoxim by Bacillus amyloliquefaciens YP6 and its
biodegradation pathway was proposed based on the transcriptomic data [86]. They ob-
served the upregulation of oxidase, hydrolase and NADPH- cytochrome P450 reductase
genes for hydrolysis, oxidation and dealkylation of phoxim. Metatranscriptomic analysis of
a two-cell Canadian biobed system identified diverse xenobiotic-degrading bacterial phyla
such as Sphingopyxis, Mesorhizobium, Oligotropha, Stenotrophomonas, Afipia and Pseudomonas
having an important role in the degradation of xenobiotics [70].
Metabolites 2022, 12, 818 8 of 27

3.3. Proteomics and Metaproteomics

Proteomics is the study of all the proteins expressed in an organism, and metapro-
teomics/community proteomics is the large-scale study of identifying and quantifying
proteins from microbial communities [87]. Protein synthesis, protein-protein interaction,
mRNA turnover, and gene expression-related studies can be performed using Proteomics.
A comparative proteomic analysis study of the strain Burkholderia zhejiangensis CEIB,
S4–3 in the absence and presence of methyl parathion, revealed the changes in protein
expression profile through 2D-PAGE [88]. The MALDI-TOF approach was used to identify
72 differentially expressed proteins; 35 and 37 in the absence and presence of methyl
parathion, respectively. They also concluded that these proteins are involved in catabolism
of aromatic compounds and detoxification of xenobiotics. The metaproteomic approach
used by An et al. [89] indicated the upregulation of 430 proteins which are mainly involved
in the detoxification of Direct Black G azo dye, such as peroxidase, aldehyde dehydrogenase
and oxidoreductase activity proteins.

3.4. Metabolomics
This approach involves the analyses of primary and secondary proteinaceous metabo-
lites produced by microbial cells under defined physiological conditions. Metabolites
produced by microbes play an essential role in intra-species and inter-species interactions.
Various methods can study metabolomics, such as metabolic flux analysis, metabolite
profiling, metabolic fingerprinting, and target analysis, to identify and quantify a wide
array of cellular metabolites [90].
Metabolomics, or global profiling of metabolite content, is a potent tool used to investi-
gate toxicant effects on organisms. The metabolic approach involves analyzing primary and
secondary proteinaceous metabolites inside the cells, tissues, or bio-fluids. Metabolomics is
the study of metabolites in biological matrices under specified conditions. Metabolomics
has recently been utilized in environmental studies to investigate metabolic alterations in
humans and other creatures exposed to various contaminants. Thus, metabolomics has
become an essential technique in research to investigate xenobiotics’ molecular effects [91].
In the metabolism of any xenobiotic compound, a series of metabolic pathways uti-
lizing a variety of enzymes is needed [92]. Recent genome analyses of bacterial strains
that digest xenobiotics have suggested that they arose recently by gathering genes for
xenobiotic degradation, with mobile genetic components playing a pivotal role in gene
recruitment [93]. However, the origins of such bacterial strains’ genes and evolutionary
processes are mainly unclear. The xenobiotic degrading enzymes are valuable for studying
protein evolution since they have a wide range of activities and their characteristics vary
substantially with a limited number of mutations [94].
The metabolomics approach was used to study the degradation mechanism of carbaryl
and other N-methyl carbamates pesticides in Burkholderia sp. strain C3 and the findings of
this study demonstrated Burkholderia sp. C3’s metabolic adaptation to carbaryl in compari-
son to glucose and nutrient broth. The metabolic changes were most prominently linked
to the biosynthesis and metabolism of amino acids, sugars, PAH lipids and cofactors [95].
In addition, a comparative metabolic approach was used to examine the microbial break-
down of cyfluthrin by Photobacterium ganghwense [96]. Soil metabolomics is an efficient
method for elucidating the intricate molecular networks and metabolic pathways utilized
by the soil microbial community. This method can also be used to identify soil pollution
biomarkers [97].
The metabolomic characterization of two potent marine bacterial isolates, Mycobac-
terium sp. DBP42 and Halomonas sp. ATBC 28, is capable of degrading phthalate and
plasticizers such ATBC, DBP and DEHP. They concluded that DBP is degraded by se-
quential elimination of the ester side chains and produces monobutyl phthalate first then
phthalate and two butanol molecules by employing a metabolomics approach [98]. Drech-
slera sp. strain 678, is capable of degrading a common additive used in gasoline, known as
methyl tertiary-butyl ether (MtBE), the organic extracts obtained from the culture filtrate
Metabolites 2022, 12, 818 9 of 27

of strain 678 were examined. The presence of two major bioactive metabolites, monocerin
and an alkyl substituted epoxycyclohexanone derivative with good antifungal activity and
bioremediation, was revealed by metabolomic analysis [99].
Metabolomics and bioinformatics technologies and databases have improved the
knowledge of microbial communities, their catabolic pathways, and the genes encoding
catabolic enzymes. Thus, it is an effective method for identifying novel metabolic pathways
and describing metabolic networks. It has been used to evaluate variation in metabolic
and catabolic gene expressions, analyze the physiology of microbial communities in var-
ied environments, and uncover the bacterial species for xenobiotic pollutant destruction.
The advance in various omics technologies such as whole genome sequencing, shotgun
metagenome sequencing, transcriptomics analysis and metabolomics identified many
xenobiotic-degrading microorganisms and their catabolic genes (Table 2). A recent study
on the transcriptomics of Fusarium verticillioides identified genes (FDB1 and FDB2) and
four associated putative gene clusters involved in the degradation of lactam and lactone
xenobiotics. The study also reported the induction of a gene cluster involved in the biosyn-
thesis of vitamin B6 upon exposure to 2-benzoxazolinone and it helps the fungus to combat
the ROS generated during the metabolization of xenobiotic compounds [100]. The omics
approaches clarify our understanding that many putative gene clusters are induced not
only to catabolize the xenobiotics directly but also that their expressions are related to many
intermediates generated during the degradation pathways.

Table 2. List of catabolic genes identified recently for xenobiotic pollutants through various omics
approaches.

Genes Identified Xenobiotic Likely Pathways Source Approaches References

Polycyclic
Alkane monooxygenase
aromatic
catalyzes the terminal
alkB, alkM, LadA, hydrocarbon Shotgun
oxidation of n-alkanes. Contaminated soil [101]
GSTs, and pcaG (PAH) degradation metagenomic
Ring-hydroxylating
and
dioxygenase degrade PAH
n-alkanes
abmG encodes
2-aminobenzoate-CoA ligase
which converts
2-Aminobenzoate to
2-Amino-benzoyl-CoA. The
MinION
2-Amino-benzoyl-CoA is
abmG and anta PAH Polluted river shotgun [102]
transformed into
sequencing
Benzoyl-CoA,
Anthranilate 1, 2-dioxygenase
encoded by antA gene
converts 2-Aminobenzoate to
catechol
Trinitrotoluene (TNT) was MinION
nemA, dsrA and
Nitrotoluene probably transformed via Polluted river shotgun [102]
dsrB
2,4,6-TNT sequencing
Dechlorinated
Reductive dechlorination of
tceA and vcrA Trichloro-ethane enrichment Transcriptomics [103]
TCE to ethene
culture
Breakdown of 4-NP into
4-nitrophenol Rhodococcus sp. Genomic and
Nph acetyl co-A and succinate by [104]
(4-NP) Strain BUPNP1 transcriptomics
nitrocatechol
Transformation of o-xylene to
Rhodococcus
akb, phe and prm o-xylene 3,4-dimethylphenol and Genomics [105]
opacus R7
2-methylbenzylalcohol
Metabolites 2022, 12, 818 10 of 27

3.4.1. Analytical Approaches for Metabolite Screening and Their Use in the Detection and
Degradation of Xenobiotics
The characteristics of metabolomics data require the implementation of several tools
of bioinformatics by a particular workflow. Various approaches are utilized to separate
and characterize distinct metabolite classes (Figure 3). The major analytical techniques of
metabolomic investigations are high-throughput techniques such as GC (Gas chromatogra-
phy), HPLC (High-performance liquid chromatography), UPLC (Ultra-performance liquid
chromatography), and CE (Capillary electrophoresis) with MS (mass spectroscopy) and
NMR spectroscopy which enable the isolation, detection, characterization, and quantifi-
cation of such metabolites and associated metabolic pathways [51,106]. Plumb et al. [107]
first combined the multivariate data analysis and LC-MS to detect xenobiotics metabolites;
numerous xenobiotic investigations have used UPLCMS-based metabolomics for further
studies. Among different analytical techniques, LC-MS (Liquid chromatography-mass
spectroscopy) and NMR have been employed extensively in metabolomic studies [108–110].
Many analytical procedures are generally required to achieve comprehensive data due
to the metabolites’ diverse chemical characteristics. A single extract of metabolites from
biological materials can contain thousands of metabolites. In untargeted metabolomics, it
is typically required to segregate metabolites using an analytical column based on their
chemical characteristics [106].

Figure 3. Workflow of Metabolomics. The first step of the metabolomics workflow is compound
detection; by employing mass spectrometry, NMR, FTIR, etc. The second step is data pre-processing,
which aims to improve the signal-to-noise ratio and quality of spectra by noise reduction, baseline
correction, peak detection and integration. The third step is data processing through data normaliza-
tion to reduce technical bias through various software such as MZmine, XCMS, Progenesis QI, etc.
The fourth step is a statistical analysis to detect the expressed metabolite, followed by the fifth step,
which is function analysis that interconnects metabolites to biological pathways. The final step is
integrating metabolomics data to omics data (omics data integration) to understand the mechanism
of action.
Metabolites 2022, 12, 818 11 of 27

Many researchers have found these techniques very helpful in identifying substances
and metabolites useful in the detection and degradation of xenobiotics, ref. [111] identified
three oxidative products and two cellular metabolites by Gas Chromatography-Mass Spec-
trometry capable of debromination and mineralizing 2, 4, 6-tribromophenol (TBP). Chen
and Kim [108] used LC-MS, for metabolomic investigations of XIT (xenobiotic-induced
toxicities). Rodríguez-Robledo et al. [112] determined endocrine disruptors atrazine and
propazine metabolites in seminal human plasma by LC-ESI-MS/MS. Lee et al. [113] ana-
lyzed the proteome of the PAH-degrading bacterium Sphingobium chungbukense. This strain
displayed exceptional aromatic compound destruction capabilities and it was also observed
that 2-DE and MALDI-TOF-MS effectively analyze xenobiotic chemicals such as phenan-
threne, naphthalene, and biphenyls (PNB), and their related proteins. The 5-carboxylated
diclofenac could be a crucial intermediary for the complete biodegradation of diclofenac
(xenobiotic) via 2,6- dichloroanailine and 3-(carboxymethyl)-4-hydroxybenzoic acid by
a microbial consortium. The carboxylated diclofenac intermediate could be extracted
and identified by LC-MS/MS-TOF [114]. Bhattacharyya et al. [115] implemented modi-
fied QuEChERS-GC-MS-LC-MS/MS technique for screening several classes of multiple
pesticides in betelvine and estimating public risk.

3.4.2. Miscellaneous Methods Used in Detection of Xenobiotics

Appropriate extraction and analytical methods for the separation and determination
of xenobiotic and derivative mixtures are critical, and they must be fast, accurate, and
affordable [17]. In the recent past, there has been noticeable progress in the development
of sample preparation techniques such as quick, easy, cheap, effective, rugged, and safe
(QuEChERS), dispersive liquid-liquid microextraction (DLLME), focused ultrasonic solid-
liquid extraction (FUSLE), solid phase extraction (SPE), solid phase microextraction (SPME),
stir bar sorptive extraction (SBSE), hollow-fiber liquid phase microextraction (HFLPME)
and many others [116].
QuEChERS analyzes multi-residue pesticides, antibiotics, hormones, mycotoxins,
polycyclic aromatic hydrocarbons, and persistent organic pollutants such as dioxins and
polychlorinated biphenyls in food and environmental matrices. QuEChERS is paired with
GC–MS or LC–MS for high selectivity, sensitivity, and specificity [117]. Solid phase extrac-
tion (SPE) encompasses preparation strategies for organic pollutants from environmental
matrices. Pharmaceuticals, pesticides, carbamate, bisphenols, and phthalate acid esters
are analyzed using this technique [118]. In contrast, solid-phase microextraction (SPME)
allows simultaneous sampling and sample preparation and is used to analyze pesticides,
polycyclic aromatic hydrocarbons, phenols, amines, and polychlorinated bisphenols in food
and environmental samples [119]. The stir bar sorptive extraction (SBSE) is used to deter-
mine pesticides, pharmaceuticals, polycyclic aromatic hydrocarbons, phenols, alkylphenols,
chlorophenols, bisphenol A, and mycotoxins present in the environment and food [120].
HFLPME with a porous hollow-fiber membrane is used to analyse lead, arsenic,
medicines, and other organic substances in environmental, clinical, and biological samples,
petroleum products, pharmaceuticals, and food. It works with chromatography, elec-
trophoresis, molecular and atomic spectrometry, and electrochemistry instruments [121].
DLLME is applied for organic compounds such as phthalate esters or parabens and metal
ions such as cadmium, selenium, and lead. Pesticide analysis is used to look for chlorophe-
nols and endocrine-disrupting phenols and medicines [122]. FUSLE can identify inorganic,
organometallic, and organic substances in environmental samples, such as polycyclic aro-
matic hydrocarbons, PCBs, phthalate esters, and nonylphenols. It can also detect endocrine
disruptors (bisphenol A and alkylphenols) in sewage sludge [123].
 4. Role of Microorganisms in Xenobiotic Degradation
Metabolites 2022, 12, 818 12 of 27
Chemical contamination can be cleaned up using biological organisms in a process
known as bioremediation. The biotransformation of xenobiotics in soils, sediments, and
water bodies relies heavily
4. Role ofon microorganisms.
Microorganisms Bioremediation
in Xenobiotic Degradation uses the biological sys-
tems of living creatures (bacteria, fungi, and can
Chemical contamination plants) and up
be cleaned enzymes [124,125].
using biological Microorgan-
organisms in a process
known as bioremediation. The biotransformation of xenobiotics
isms have an incredible ability to catabolize with the help of various genes, enzymes, and in soils, sediments, and
water bodies relies heavily on microorganisms. Bioremediation uses the biological systems
degradation pathways involved
of living in (bacteria,
creatures biodegradation. Numerous
fungi, and plants) microbes
and enzymes such
[124,125]. as Alcali-
Microorganisms
genes, Cellulosimicrobium,
have Microbacterium,
an incredible abilityMicrococcus,
to catabolize with Methanospirillum,
the help of various Aeromonas, Sphin-
genes, enzymes, and
degradation pathways involved in biodegradation. Numerous
gobium, Flavobacterium, Rhodococcus, Aspergillus, Penicillium, Trichoderma, Streptomyces, microbes such as Alcaligenes,
Cellulosimicrobium, Microbacterium, Micrococcus, Methanospirillum, Aeromonas, Sphingobium,
Rhodotorula, Candida and Aureobasidium
Flavobacterium, have
Rhodococcus, been isolated,
Aspergillus, characterized
Penicillium, and have
Trichoderma, Streptomyces, exhib-
Rhodotorula,
ited an excellent ability to biodegrade
Candida a variety
and Aureobasidium have been ofisolated,
xenobiotic pollutants
characterized and havefound in an
exhibited soil/wa-
excellent
ability to biodegrade a variety of xenobiotic pollutants found
ter settings [79]. However, few representative microbial enzymes are involved in detoxi- in soil/water settings [79].
However, few representative microbial enzymes are involved in detoxifying xenobiotics,
fying xenobiotics, including
includingcytochrome P450s,
cytochrome P450s, laccases,
laccases, cellulase,
cellulase, phytase,phytase,
proteases, proteases, and
and lipases shown
lipases shown in Figure 4. These
in Figure enzymes
4. These enzymescan degrade
can degrade aromatic
aromatic hydrocarbons,
hydrocarbons, dyes and dyes and
halogenated
compounds through various
halogenated compounds through various mechanisms. mechanisms.

Figure 4. Microbial enzymes inMicrobial

Figure 4. xenobiotic management.
enzymes This figure
in xenobiotic management. summarizes
This a few
figure summarizes a fewrepresenta-
representative
tive enzymes and their corresponding microbial sources involved in xenobiotic detoxification.
enzymes and their corresponding microbial sources involved in xenobiotic detoxification.

4.1. Xenobiotic Degrading Enzymes Associated with Bacteria

Bacteria are known for their extraordinary capacity to multiply rapidly in large num-
bers and withstand harsh environmental conditions [126]. Recent genomic investigations
of strains of bacteria that digest xenobiotics suggest that they evolved by accumulating
genes for xenobiotic destruction. Bacterial species such as Pseudomonas, Escherichia, Sphin-
gobium, Pandoraea, Rhodococcus, Gordonia, Bacillus, Moraxella, Micrococcus (aerobic bacteria),
Pelatomaculum, Desulfotomaculum, Syntrophobacter, Syntrophus, Desulphovibrio, Methanospi-
rillum, Methanosaeta (anaerobic bacteria), etc., have been isolated from soil and characterized
Metabolites 2022, 12, 818 13 of 27

4.1. Xenobiotic Degrading Enzymes Associated with Bacteria

Bacteria are known for their extraordinary capacity to multiply rapidly in large num-
bers and withstand harsh environmental conditions [126]. Recent genomic investigations
of strains of bacteria that digest xenobiotics suggest that they evolved by accumulating
genes for xenobiotic destruction. Bacterial species such as Pseudomonas, Escherichia, Sphin-
gobium, Pandoraea, Rhodococcus, Gordonia, Bacillus, Moraxella, Micrococcus (aerobic bacteria),
Pelatomaculum, Desulfotomaculum, Syntrophobacter, Syntrophus, Desulphovibrio, Methanospiril-
lum, Methanosaeta (anaerobic bacteria), etc., have been isolated from soil and characterized
for their biodegradation potential of xenobiotic compounds (DDT, lindane, PCBs, TNT and
crystal violet) [127]. The human intestinal microbiota has a direct xenobiotic-metabolizing
potential, but it can also affect the expression of host metabolizing genes and the activity
of host enzymes [79]. Based on the examination of 16S rRNA and gyrB gene sequences,
strain 1D of thermotolerant bacteria isolated from oil-contaminated soil at a refinery was
identified as Gordonia sp. [72].
Aromatic compounds (xenobiotics) act as an electron-donating substrate in the lack
of oxygen (anaerobic condition), and microbes grow by oxidizing these substances in
the existence of an electron acceptor. Enzymatic biodegradation begins with selecting
an enzyme for a bioremediation application; it must be capable of degrading the target
pollutants into less-toxic products [127]. Many bacteria species can potentially change the
hazardous xenobiotic substances into less or nontoxic substances with the help of specific
enzymes present inside them.
The present review aims to report recent investigations on microbial degradation of
aliphatic and aromatic hydrocarbons. The biodegradation of different types of hydrocar-
bons requires distinct enzymes’ due structural variation of these xenobiotic compounds at
a molecular level [128]. The degradation of aliphatic hydrocarbons occurs either through
monooxygenases which add single oxygen to the terminal methyl functional group or
dioxygenase, which adds two oxygen atoms resulting in the peroxide formation converted
to a fatty acid. The fatty acid molecule oxidizes to form TCA cycle intermediates that
further metabolize to CO2 and H2 O. The aromatic hydrocarbons are slowly degradable
due to low solubility, production of toxic metabolites and metabolite repression [129]. At
first, these compounds are converted to cis-dihydrodiols and cleaved by dioxygenase
enzymes either through ortho- or meta-cleavage pathways. Then, the fission of aromatic
rings occurs between the hydroxyl groups in ortho-cleavage and adjacent to hydroxyl
groups in meta-cleavage pathways, finally leading to intermediates of central pathways. A
few recently isolated bacteria and their associated enzymes responsible for aliphatic and
aromatic hydrocarbons along with their mechanism of action are listed in Table 3.

4.2. Xenobiotic Degrading Enzymes Associated with Fungi

In addition to bacteria, fungi have a role in organic pollutant remediation. They have
unique characteristics that make them ideal microorganisms for bioremediation procedures.
They can reduce pollutant concentrations by physically adsorbing various contaminants
via a thick cell wall composed of polymers such as chitin and cellulose. The fungal
decomposition of xenobiotic compounds has highlighted the importance of the intracellular
enzymatic system’s involvement in xenobiotic transformation (Table 4) [79]. These fungi
benefit various activities, including biofuel degrading, environmental management, and
industries such as food, paper, beverages, textiles, etc.
Metabolites 2022, 12, 818 14 of 27

Table 3. Bacterial Enzymes involved in the transformation of various aliphatic and aromatic hydrocarbons.

Mechanism of
Xenobiotic Bacteria Enzyme Novelties/Inventions References
Degradation
Xanthobacter
Aliphatic autotrophicus GJ10
hydrocarbons Rhodococcuserythropolis The genes encoding alkane oxidation in P. oleovorans
R. erythropolis Y2 (England) Haloalkane Nucleophilic substitution GPo1 are located on the OCT-plasmid in two operons. It
Haloalkane indicates the horizontal transfer of catabolic genes across
R. rhodochrous NCIMB13064 dehalogenase reaction to catalyze the [130]
(1, 2-dichloroethane)
Corynebacterium strain m15 (DhlA) displacement of Cl− the gram-border. The study emphasizes that horizontal
mobilization is faster than the generation of novel
Alkane Oxidation of the terminal
Medium- and Pseudomonas catabolic pathways evolved by nature.
hydroxylase carbon atom yielding
long-chain alkanes oleovorans GPo1
(AlkB, AlkM) an alcohol
Catalyzes the
Protein fusion strategies used to
hydroxylation and possibly
Sterol R. jostii RHA1 Oxygenase identify novel activities of cytochrome P450 for [131]
further oxidation of the C26
biotransformation
atom of sterols
Aromatic
hydrocarbons
PCR and cloning approach using basidiomycetes
Oxidize phenolic and
specific primers [132]
methoxyphenolic acids,
Azo dyes Ganoderma sp. determine the diversity of laccase and
decarboxylate them and
peroxidase-encoding genes, revealing the occurrence of
Laccase attack their methoxy groups
several laccase isozymes.
Ability to remove This study recommends the use of
organic substrate the consortium of versatile laccase and peroxidase-based
Estrogen Pseudomonas putida strains electrons and biocatalyst for [133,134]
ultimately reduce complete removal of multiple
dioxygen molecules estrogens at faster rates.
Metabolites 2022, 12, 818 15 of 27

Table 3. Cont.

Mechanism of
Xenobiotic Bacteria Enzyme Novelties/Inventions References
Degradation
Nitro aromatic
Compounds
(2-nitrophenol, Xenophilus azovorans KF46F
The metaproteomics approach was employed to find out
4-nitrobenzoic acid, Enterococcus faecalis
Azoreductases Reduction of azo-bonds the microbial key players in compost-treated
2-nitro-benzaldehyde, Geobacillus stearothermophilus
bioremediation
and 3-nitrophenol) Pseudomonas KF46
Catechol is first transformed
Catechol and Chlorocatechol into a ring-cleaved product,
Pseudomonas sp. [79,135]
chlorocatechol 2,3-dioxygenase i.e., 2-hydroxymuconic
semialdehyde.
Cleave between the two
hydroxyl substituents of The study identifies the upregulation of BuP34O (a gene
Acinetobacter calcoaceticus
Protocatechuate protocatechuic acid; with the encoding for protocatechuate 3,4-dioxygenase—P34O, a
Protocatechuate Nocardia sp.
3,4 Dioxygenase incorporation of molecular key enzyme in the β-ketoadipate pathway) during TNT
Buttiauxella sp. S19-1
oxygen to form degradation.
β-carboxymuconate
Polyaromatic
hydrocarbons Pseudomonas putida (strains: NCIB
9816-4, G7, AK-5, PMD-1, and The study presents insights into strain optimization for
CSV86), Naphthalene
competent, rapid, and complete bioremediation. The
dioxygenase Oxidation of one of the [136]
Pseudomonas stutzeri AN10, study also highlights that understanding at the
Naphthalene Pseudomonas fluorescens PC20, and (NDO) and ring- aromatic rings of naphthalene
biochemical and molecular levels will help identify a
other spp. (ND6 and AS1) hydroxylating using molecular oxygen
suitable host that can be further genetically engineered
dioxygenase
for efficient bioremediation of priority pollutants
Metabolites 2022, 12, 818 16 of 27

Table 4. Fungi and their working enzymes involved in Xenobiotic transformation.

Xenobiotic Fungi Enzyme Mechanism of Degradation Novelties/Inventions Reference

β-lactamase producing genes were
It hydrolyzes an aromatic
Aromatic Hydrocarbon widespread, creating a vast reservoir
Fusarium verticillioides Lactamases polyketide into [100]
β-lactam for genetic transfer between soil
endocrocin-9-anthron
microorganisms.
Laccases, tyrosimases,
manganese peroxidases Bjerkandera adusta possess high
De-alkylation of atrazine
(MnP), manganese potential with a removal efficiency of
Atrazine Bjerkandera adusta results in fragments of [137]
independent peroxidases the xenobiotic compound (atrazine) up
adelhyde and ketone
(MiP) and lignin to 92%.
peroxidases
Atrazine It helps in the detoxification
N-acetyltransferae and Acetyl coenzyme A- and malonyl
Monocrotophos Fusarium spp. and degradation of aromatic [138]
N-malonyltransferase coenzyme A-dependent detoxification
DDT amines
Trichoderma harzianum, Aspergillus fumigatus,
Lactase, LiP, MnP, epoxide By peripheral degradation PHA’s molecular structure was altered
Cunninghamella elegans, Aspergillus niger,
Aromatic compounds, hydrolases cytochrome pathways organic pollutants by the action of the enzyme, leading to
Penicillium sp., Cunninghamella elegans,
aliphatic hydrocarbons and P450 monoxygenase, are gradually transformed, the ring-cleavage processes that [139]
Aspergillus ochraceus, Trametes versicolor,
PAHs dioxygenases, protease and and many intermediate produced several intermediate
Penicillium sp. RMA1 and RMA2 and
lipase products are formed components
Aspergillus sp. RFC-1
Responsible for pectin Studies that have been conducted on C.
Chlorpyrifos hydrolase, degradation by catalyzingthe cladosporioides discovered bioactive
Pectin methylesterase demethoxylation of the compounds including
Chlorpyrifos Cladosporium cladosporioides [140]
(PME) and homogalacturonan chain of p-methylbenzoic acid, EP and
polygalacturonase (PG) pectin to release methanol calphostin C as well as enzymes such
and acidic pectin as PME, PG and chlorpyrifos hydrolase
Helps in the formation of The non-specific nature of these
Lignin,
semi-quinone intermediate enzymes makes them capable of
Polychlorinated biphenyls
Trametes versicolor, Phanerochaete during the oxidation of degraders a diverse group of
(PCBs), Petroleum Lignin peroxidase, versatile
chrysosporium, lignin-derived hyroquinone environmental pollutants, including
hydrocarbons, peroxidase, laccase and [125,141]
Rigidoporous lignosus and by laccase. It cleaves C-C dioxins, polychlorinated biphenyls
PAHs, trinitroluenes, manganese peroxidise
Pleurotus ostreatus bonds and oxidizes benzyl (PCBs), petroleum hydrocarbons,
industrial dye effluents,
alcohols to aldehydes or PAHs, trinitroluenes, industrial dye
herbicides and pesticides
ketones effluents, herbicides and pesticides
Metabolites 2022, 12, 818 17 of 27

Table 4. Cont.

Xenobiotic Fungi Enzyme Mechanism of Degradation Novelties/Inventions Reference

Degrades various Bio-transformation of nitroaromatic
nitroaromatic compounds by compounds and their conversion into
Nitroaromatic compounds Phanerochaete chrysosporium Peroxidases [142]
initial reduction of the nitro nontoxic metabolites via their
group tohydroxylamines metabolism
Navy blue HER, Indigoid,
Trichosporon beigelii NCIM-3326, P. It attacks phenolic subunit Lowering the amount of dye in the
triarylmethane,
chrysosporium URM6181 and Curvularia and degrades dyes, leading to effluent, showing superior rates of
azo-dibenzothiophene, Laccase [143]
lunata URM6179 Trametes hirsute and Cα oxidation, Cα-Cβ cleavage decolorization up to 98% and
N-ethylcarbozole and
Coriolopsis gallica and aryl-alkyl cleavage biodegradation rate 96%, respectively
carbozole
This study revealed that in saline
Aspergillus sydowii Degradation of synthetic medium, both fungi used
PAH and PhC and Laccase and Peroxidase benzo-α-pyrene benzo-α-pyrene and phenanthrene as [144,145]
Aspergillus destruens phenanthrene sole carbon sources and removed over
90% of both PAH
Metabolites 2022, 12, 818 18 of 27

5. Practical Use of Microorganisms in Bioremediation of Xenobiotics

The patents are highly relevant to xenobiotic degradation; many such patents were
retrieved from different databases on the basis of priority of filing and properties relevant in
use to handle xenobiotics. Therefore, the search includes publicly available databases, i.e.,
Espacenet, DPMA, USPTO, JPO, EPO, PatFT, WIPO which cover databases produced by
the Canadian Intellectual Property Office, German patents, German Patent and Trademark
Office, European Patents and Chinese Patents etc (Table 5).
Regarding the environmental threats of xenobiotic compounds, there are many proven
methods and products in the form of patents and process patents [99,146–149]. However,
with the fast-growing technologies and human needs, many products are being designed
globally, and many are not entirely degradable; therefore, scientists are working on those
with long shelf-life and poor degradative nature.

Table 5. Various patents and their properties used in the field of Xenobiotics.

Patent Patent No. Country Application Novelties/Inventions References

This study revealed the use of
the defined assorted culture of
Biotransformation
bacteria isolated through
and/or
Microbial England; enrichment on major
mineralisation of
degradation of 0 274 856 A1 European individual constituents of an [150]
each determined
waste/sludge Patent effluent, followed by mixing
constituent of the
the isolates to detoxify the
waste
complex non-degradable
effluent.
This invention is unique in
Microbial
terms of its way of selecting
degradation of
Microbial removal and using oleophilic
Germany; xenobiotic dyes
of DD290004A5 microorganisms that ensure [151]
German Patent from
xenobiotic dyes the degradation of xenobiotic
triphenylmethane
dyes, in particular, those of
compounds
triphenylmethane compounds
Detoxification of a
This invention provides
variety of
insight into symbiotic yeast
xenobiotics,
Microbial Peoria, United i.e., cigarette beetle
including
detoxification of States; (Lasioderma serricorne)
US4968620A insecticides, [152]
xenobiotics using United States NRRLY-18546 that detoxify
herbicides,
yeast Patent pesticides, herbicides,
mycotoxins, and
mycotoxins, and plant
plant toxins
poisons (allelochemicals)
(allelochemicals)
Two-phase
partitioning Causing the
Canada; The novelty of the invention is
bioreactor for the microorganism to
Canadian the two-phase concentration
degradation of a CA2216327A1 metabolize the [153]
Intellectual of xenobiotic compounds
xenobiotech xenobiotic in the
Property Office using bioreactors
(organic and aqueous phase
aqueous)
The novelty of this patent
suggests that the
co-metabolism of MTBE by
Bioremediation of Degradation of
United States; graphium and other microbial
Xenobiotics Methyl
US 6,194,197 B1 United States species having a non-specific [154]
Including Methyl Tert-Butylether
Patent P-450 cytochrome oxidase
Tert-Butylether (MTBE)
could be used for the
remediation of MTBE
contamination
Metabolites 2022, 12, 818 19 of 27

Table 5. Cont.

Patent Patent No. Country Application Novelties/Inventions References

A method of removing
contaminated groundwater is
provided which places a
Creating a biological permeable barrier
Treatment of “bio-trench” or in the path of the
United States;
contaminated “bio-curtain” to groundwater flow to contact
WO 01/32566 Al Australian [155]
groundwater using clean the contaminated
Patent
immobilized cells contaminated groundwater with
groundwater encapsulated microorganisms
which act to decontaminate
the contaminated
groundwater
Biodegrading of
Processes for making harmful
chlorinated
chemical substances harmless
organic
Environmental or less harmful by effecting a
Tokyo-Japan; compounds such
remediation of chemical change in the
EP 0 822 253 B1 European as [156]
organic substances by biological
Patent trichloroethylene
compounds methods, i.e., processes of
(TCE) and
utilizing enzymes or
dichloroethylene
microorganisms as whole
(DCE)
Effective method for
decomposing xenobiotics (X)
using a physiologically
compatible combination of at
least one fungus (A) with
Microbial Degradation of the mono-/di-oxygenase activity
Germany;
decomposition of DE10125365A1 herbicide and at least one fungus (B) [157]
German Patent
xenobiotics Isoproturon with glutathione-S-transferase
(GST) activity. An
independent claim is also
included for a combination of
decomposing (X) containing
(A) and (B).
A process for anaerobic
Denmark; microbial degradation of
World phthalic acid esters,
Anaerobic
Intellectual comprising the step of adding
microbial Degradation of
WO2006136173A2 Property to a bioreactor at least one [158]
degradation of phthalic acid esters
Organization bacterial strain, which as a
phthalic acid esters
International pure isolate capable of
Bureau anaerobic degradation of
phthalic acid esters.
Wautersia eutropha strain
JMS34, a recombinant
bacterium that can completely
Degradation or
bioremediation of degrade or mineralize
mineralization of
chlorinated pollutants such as
Chile; United pollutants such as
organic compound US 7,989,194B2 polychlorobiphenyls (PCBs), [148]
States Patent polychloro-
using recombinant bioremediation of
biphenyls
bacteria PCB-contaminated
(PCBs),
environments that contain a
bacterial inoculum of this
recombinant strain.
Metabolites 2022, 12, 818 20 of 27

Table 5. Cont.

Patent Patent No. Country Application Novelties/Inventions References

According to the present
Method for Removal of invention, it can provide a
simultaneous nitrogen kind of when in order to
Prilly,
biological removal compounds and handle the method that
Switzerland;
of nitrogen WO2013166611 xenobiotics of contains ammonia-state [159]
European
compounds and wastewaters using nitrogen waste water and
Patent
xenobiotics of aerobic granular carry out promotion when
wastewaters biomass biological nitrogen is removed
nitration reaction.
The present solution is a
Removal of
Purification of soil Warszawa- natural method of removing
contaminants from
contamination Poland; hazardous pollutants from the
EP 2 788 512 B1 soil, as well as a [149]
using bacterial European environment without
method of soil
strain Patent introducing synthetic
treatment
products.
The bacterium Arthrobacter
ureafaciens liulou 1 (CGMCC
9667) possesses a unique
Soil and Plant
combination of high
remediation using China; Chinese atrazine
CN104762227A atrazine-degrading activity [160]
Atrazine Patent degradation-
and can colonize plant roots
degrading bacteria
after seed inoculation and
traits of plant
growth-promoting bacterium.
The activity-based probes
Probes for labeled only their target active
specifically enzymes involved in
Xenobiotic United States; identifying target xenobiotic metabolism and
US 2019/0100792
metabolism and United States active enzymes therefore provide a [150]
A1
associated enzyme Patent involved in measurement of true protein
xenobiotic functional activity rather than
metabolism transcript or protein
abundance.
Described herein are
engineered cells, enzymes,
GE bacteria can
Bioremediation of United States; methods of use, and bee bread
hydrolyze ester
xenobiotics in the US2021378263A1 United States incorporating engineered cells [161]
bonds or remove a
honey bee hive Patent and enzymes as described
carboxyl group
herein to address honey bee
hive contamination
The model facilitates
metabolic modeling and
In-vitro model of enables a better
the human gut Modifications of understanding of the
microbiome to United States xenobiotics by structure and function of the
US20200370005 [162]
understand the Patent intrinsic gut human gut microbiome and
Impact of microbiota modifications of xenobiotics
xenobiotics by intrinsic gut microbiota,
such as biotransformation and
bioaccumulation.
Metabolites 2022, 12, 818 21 of 27

6. Conclusions and Future Perspective

Omics approaches are an effective way to understand environmental toxicology and
its remediation by employing a hybrid or integrated approach to decipher various effects
of xenobiotics and other pollutants on flora, fauna including various ecosystems. The
advantages include a better understanding of catabolic genes, degradative enzymes and
involved metabolic pathways. In xenobiotic-contaminated soil/water ecosystems, micro-
bial communities have the potential to play an influential role in mediating the successful
biodegradation processes. Various molecular techniques provide potential measures to
tackle the in-depth assessment of microbial communities at all levels, from the gene to
molecule and organism to ecosystem. Many microbes with strong catabolic capability
have been identified and described. The omics technique has uncovered many enzymes,
especially those produced by unculturable microbes. These innovative steps have discov-
ered various biocatalysts that are organically fitted to industrial restrictions. In this review,
several patents have been discussed that employed either single isolates or mixed microbial
strains to biotransform xenobiotics from contaminated environments. Resistant microbial
technologies must be considered from a practical perspective; however, there is still some
controversy on their field applications.
However, more research is required to accomplish exceptional advancements in biore-
mediation by developing novel genetically modified strains with potent catabolizing genes
to have xenobiotics-free ecosystems. Furthermore, the combined approach of green nan-
otechnology and microbe-mediated bioremediation must be given close attention to combat
xenobiotic pollution. Sustainable policies should be developed frequently using contempo-
rary technologies; they need support from government, policymakers, and stakeholders.

Author Contributions: Conceptualization, R.M., N.P., A.K., M.A.A., A.K.P. and S.K.; methodology,
R.M., N.P., A.K., M.A.A., S.K., G.R., S.S.B., J.U. and M.N.A.; software, R.M., N.P., A.K., M.A.A.,
S.K., G.R., S.S.B., J.U. and M.N.A.; resources, R.M., N.P. and M.N.A.; data curation, R.M., N.P., A.K.,
M.A.A., S.K., G.R., S.S.B., J.U., A.K.P. and M.N.A.; writing—original draft preparation, R.M., N.P.,
A.K., M.A.A., S.K., G.R., S.S.B. and M.N.A.; writing—review and editing, R.M., N.P., A.K., M.A.A.,
S.K., G.R., S.S.B., J.U. and M.N.A.; supervision, R.M., N.P., and M.N.A.; project administration, R.M.,
N.P. and M.N.A.; funding acquisition, R.M., N.P., J.U. and M.N.A. All authors have read and agreed
to the published version of the manuscript.
Funding: This research received no external funding.
Acknowledgments: The authors are grateful to the Department of Biotechnology (DBT), Min-
istry of Science and Technology, New Delhi, India (Vide order number BT/PR24972/2017) for
financial assistance.
Conflicts of Interest: The authors declare no conflict of interest.

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