6/3/24, 14:18 Sistemas transportadores de membrana bacteriana para compuestos aromáticos: Regulación, ingeniería y aplicaciones

biotecnológicas - S...

ScienceDirecf

Biotecnología Avances
Volumen 59, octubre de 2022,107952

Documento de revisión de la investigación

Sistemas transportadores de membrana bacteriana para

compuestos aromáticos: Regulación, ingeniería y
aplicaciones biotecnológicas
Ishmael Mutanda, lianzhonq Sun, Jianxionq Jiang, Daochen Zhu o, jgj

Mostrar más xz

Compartir 55 Citar

https://doi.org/10.1016/j.biotechadv.2022.107952 71
Obtener derechos y contenido 71

Momentos destacados
• Transportadores de membrana bacteriana para compuestos aromáticos relacionados con la lignina y xenobióticos.

• Canales generales y específicos del sustrato, transportadores FadL y TonB

• Los transportistas primarios y secundarios son cruciales en la importación/exportación de aromáticos.

• Se presenta una visión general de la regulación transcripcional y la ingeniería del transportador.

• Aplicaciones biotecnológicas para la biorremediación y la biotransformación de biomasa

Abstracto
Los compuestos aromáticos son omnipresentes en la naturaleza; son los componentes básicos de la abundante lignina y
constituyen una proporción sustancial de sustancias químicas sintéticas y contaminantes orgánicos. La absorción y
degradación de compuestos aromáticos por las bacterias tiene relevancia en la biorremediación, el reciclaje de plásticos de
base biológica y la conversión microbiana de biomasa lignocelulósica en productos químicos de alto valor. Si bien se han
logrado avances notables en la comprensión del metabolismo aromático en los biodegradadores, los sistemas de transporte
de membranas responsables de la absorción y el eflujo de los compuestos aromáticos y sus productos de degradación
todavía no se conocen bien. Los transportadores de membrana son responsables del reconocimiento inicial, la absorción y
el flujo de compuestos aromáticos; por lo tanto, además de controlar la afluencia y el eflujo, el transportador

https://www.sciencedirect.com/science/article/abs/pii/S0734975022000489 1/6
 6/3/24, 14:18 Sistemas transportadores de membrana bacteriana para compuestos aromáticos: Regulación, ingeniería y aplicaciones
biotecnológicas - S...

también forma parte de los mecanismos de tolerancia al estrés a través de la excreción de metabolitos tóxicos. Esta
revisión discute avances significativos en nuestra comprensión de la naturaleza e identidad de los sistemas
membranetransporter bacterianos para aromáticos, la base molecular y estructural del reconocimiento del sustrato,
mecanismos de translocación, regulación funcional, y aplicaciones biotecnológicas. La mayoría de estos desarrollos fueron
habilitados a través de la disponibilidad de estructuras cristalinas, avances en biofísica computacional, secuenciación del
genoma, estudios de omics, bioinformática y biología sintética. Proporcionamos una visión general completa de los
conocimientos recientemente reportados sobre los sistemas de transporte aromático en las bacterias, señalar lagunas en
nuestra comprensión de los mecanismos de translocación subyacentes, destacar las limitaciones existentes en el
aprovechamiento de los sistemas de transporte en aplicaciones de biología sintética, y sugerir futuras direcciones de
investigación.

Resumen gráfico

Descargar : Descargar imagen de alta

resolución (323KB)
Descargar : Descargar imagen de tamaño
Introducción
El anillo de benceno es una de las estructuras químicas más comunes en la naturaleza. Debido a su presencia en la
biomasa lignocelulósica, el petróleo y el carbón, los aromáticos constituyen más del 20% de la biomasa de la tierra -
la segunda fuente abundante de carbono después de los carbohidratos (Diaz et al., 2013). Los compuestos aromáticos
contaminantes (PAC) de interés ambiental, incluidos los xenobióticos (ajenos a la naturaleza) proceden
principalmente de fuentes antropogénicas, mientras que la lignina derivada de la materia vegetal es la mayor fuente
natural de compuestos aromáticos (compuestos aromáticos derivados de la lignina, LDCA). Fuentes antropógenas que
aportan PAC tóxicos y persistentes incluyen la combustión de combustible, incineradores de desechos, automóviles,
minería, derrame de petróleo, gasificación de carbón, tratamiento de madera, agricultura intensiva, actividades
industriales, industrias químicas, farmacéuticas y de procesamiento, pasta de papel y blanqueo de papel (Díaz, 2004;
Jin et al., 2020; Rieger et al., 2002).

PACs, including polychlorinated biphenyls (PCBs), chlorinated phenols, BTEX (benzene, toluene, ethylbenzene, and
xylene), polycyclic aromatic hydrocarbons (PAHs), monoaromatic hydrocarbons (MAHs), and substituted aromatics
(Fig. 1) are arguably the most dominant in the environment (Samanta et al., 2002; Vidali, 2001). They represent the
bulk of persistent environmental pollutants that threaten natural ecosystems and pose a health hazard to human and
animal life due to their toxicity, mutagenicity, carcinogenicity, and effects on reproductive health (Adam et al., 2021;
Boffetta et al., 1997; Goldman et al., 2001; Samanta et al., 2002; Seo et al., 2009; Zhang et al., 2019). The inexorable
rise in the use of plastics from the last decades greatly exacerbated PAC contamination in drinking water, food and
air. Removal of these toxic PACs from contaminated environments poses a considerable challenge, especially in this
era of heavy industrial processing and intensive agricultural production. The use of microorganisms to
remove/detoxify these pollutants (bioremediation) is preferred over other methods because it is cheaper,

6/3/24,14:18 Bacterial membrane transporter systems for aromatic compounds: Regulation, engineering, and biotechnological applications - S...

https://www.sciencedirect.com/science/article/abs/pii/S0734975022000489 2/6
 sustainable, and environmentally friendly (Hu et al., 2021; Ripp et al., 2000; Watanabe, 2001). Even more exciting is
the potential of biotechnological plastic degradation and recycling (Tournier et al., 2020; Wei et al., 2020).

In addition aromatic biodegraders can be harnessed for the biotechnological valorization of diverse bioresource
materials such as lignin coal petroleum organic matter humic acid and waste streams to produce high-value bio-based
chemicals and end products. Aromatic compound degradation ability has been identified across several bacterial
genera: Achromobacter, Aeribacillus, Mycobacterium, Pseudomonas, Sphingomonas, Bacillus, Acinetobacter,
Alcaligenes, Rhodococcus, Corynebacterium, Sphingobium, Methermicoccus, etc. (Durante-Rodriguez et al., 2018;
Kanaly and Harayama, 2010; Ma et al., 2015; Mayumi et al., 2016; Xu et al., 2018; Zhu et al., 2018). Bacteria have
evolved exceptional systems to scavenge aromatic compounds from the environment and depolymerize, metabolize
and assimilate them as nutrients through successive oxidation and ring-opening reactions or anaerobic reductive
reactions (Boll et al., 2002; Durante- Rodriguez et al., 2018; Fuchs et al., 2011; Zhu et al., 2020). Substantial gains
have been realized in the elucidation of biodegradative pathways in biodegraders (Diaz et al., 2013; Kanaly and
Harayama, 2010; Seo et al., 2009; Zhu et al., 2021b; Zhu et al., 2017), and in our understanding of the enzymes
involved in the degradation of LDACs (Leynaud Kieffer Curran et al., 2022; Weiss et al., 2020; Zhu et al., 2022) and
PACs (Hu et al., 2021; Mutter and Zylstra, 2021; Yeom et al., 2021; Yoshida et al., 2016; Zhu et al., 2021a).
Advances in our understanding of the funneling pathways in biodegraders have inspired active research in engineering
these pathways for microbial transformation of lignocellulosic biomass streams (Becker et al., 2018; Davis and Moon,
2020; Linger et al., 2014; Weiss et al., 2020; Zhu et al., 2021b) and in development of more efficient degraders for
environmental applications (Aso et al., 2006; Tournier et al., 2020; Wang et al., 2021)

While knowledge on biodegradative pathways is accumulating at accelerated rates, there is a dearth of information on
equally crucial bacterial membrane transporter systems that facilitate and control the uptake and efflux of these
aromatic compounds. Bacterial membranes form an effective barrier for the entrance of both hydrophilic and
hydrophobic compounds. The exchange between extracellular and intracellular environments is through specialized
pores and channels in various membrane transporter proteins. Passive permeation of small, uncharged aromatic
compounds into cells via simple diffusion is possible at higher extracellular concentrations (Vermaas et al., 2019) or
at lower pH in the case of aromatic acids (Nichols and Harwood, 1997). However, uptake of the majority of aromatic
compounds is facilitated by specialized transporter systems, especially considering the low environmental
concentrations of these compounds and the need to regulate intracellular levels.

Evidence of the indispensability of membrane transporter systems in translocation of aromatic compounds come from
multiple sources: (1) gene disruption mutations of transporters (Nogales et al., 2011) or their regulatory elements
(Craven et al., 2009; Tumen-Velasquez et al., 2019) cause inability to grow on aromatic substrates, (2) proton gradient
inhibitors, ATPase inhibitors, and efflux pump inhibitors abolish uptake/efflux of metabolites, (3) complementation of
transporter genes can rescue phenotypes of gene disruption mutants, and (4) overexpression of transporter systems
improves uptake/efflux and growth on respective substrates.

This review provides a comprehensive discussion on bacterial transporter systems for uptake and efflux of aromatic
compounds. We focused on transporter systems for LDACs and PACs due to their biotechnological and ecological
significance. The review first discusses outer membrane (OM) and inner membrane (IM) uptake systems, followed by
efflux pumps, and proceeds to descriptions of regulatory components and functional regulation of genes encoding
transporters. Lastly, we highlight biotechnological applications of transporters and their regulatory elements, discuss
knowledge gaps, and suggest future research directions.

6/3/24,14:18 Bacterial membrane transporter systems for aromatic compounds: Regulation, engineering, and biotechnological applications - S...

Section snippets

Membrane transporter systems for aromatic compounds in bacteria

Uptake and efflux of aromatic compounds across the bacterial membrane are mediated by a versatile and coordinated
combination of active and passive transporter systems. The OM of gram-negative bacteria and IM/cytoplasmic
https://www.sciencedirect.com/science/article/abs/pii/S0734975022000489 3/6
 membrane of gram-negative and gram-positive bacteria act as effective permeability barriers for substances that
enter/exit the cell. On a very simple level, membrane transporters can be divided into passive and active classes.

About 30% of all integral membrane proteins in...

Transcriptional regulation of the bacterial transporter systems

Due to their crucial function as gatekeepers of membrane traffic and as part of an adaptive response against toxic
compounds, membrane transporters are tightly regulated at the transcription level. Omics data show global
reorganization of the membrane transporters in response to treatment with aromatic compounds (Roma-Rodrigues et
al., 2010). Bacterial genes for catabolic and transporter genes are often arranged in operonic gene clusters
characterized by a common promoter and a common,...

Engineering the aromatic transporter systems towards biotechnological applications

The development of engineered microbes for microbial transformation of plant biomass into value-added renewable
chemicals and efficient degradation of recalcitrant pollutants has attracted a lot of attention in the context of
renewable energy, renewable chemicals, bioremediation, biotechnological waste recycling, and other ecological
applications. However, primary research has mainly focused on degradative pathways of aromatic compounds in
biodegraders, while the transporter system received...

Prospects and challenges

Over the past few years, several transporter systems were identified and functionally characterized through several
approaches and tools including genetic, biochemical, synthetic biology, structural, computational biophysics,
bioinformatics, and high-throughput sequencing. However, compared to advances in our understanding of aromatic
compound degradation pathways and their regulatory mechanisms in many microorganisms, the identification and
characterization of transporter systems for the same...

Conclusion
This review provides a comprehensive overview of bacterial membrane transporter systems that mediate the uptake
and efflux of aromatic compounds with biotechnological and ecological relevance. We focused on transporter systems
involved in importing and exporting LDACs and pollutant aromatic compounds in biodegraders. The review provided
an integrated view of our current understanding of OM and IM/cytoplasmic membrane transporter systems for
aromatic hydrocarbons based on genetic, biochemical,...

Disclosure statement
The authors have no conflict of interest...

6/3/24,14:18 Bacterial membrane transporter systems for aromatic compounds: Regulation, engineering, and biotechnological applications - S...

Declaration of Competing Interest

The authors declare no conflict of interest....

Acknowledgments
This work was supported by the Key Research and Development Program of Jiangsu Province (Grant No.
BE2021691), and the Priority Academic Program Development of Jiangsu Higher Education Institutions....

Recommended articles
https://www.sciencedirect.com/science/article/abs/pii/S0734975022000489 4/6
 References (187)

E. Arias-Barrau et at.
A Two-component Hydroxylase Involved in the Assimilation of 3-Hydroxyphenyl Acetate in Pseudomonas
putida *
The Journal of biological chemistry (2005)

S. Biswas et al.
Crystal structure of the outer membrane protein OpdK from Pseudomonas aeruginosa
Structure (2008)

M. Boll et al.
Anaerobic oxidation of aromatic compounds and hydrocarbons
Curr. Opin. Chem. Biol. (2002)

D. P. Cogan et al.
Structural basis of transcriptional regulation by CouR, a repressor of coumarate catabolism, in
Rhodopseudomonas palustris
J. Biol. Chem. (2018)

K. Davis et al.
Tailoring microbes to upgrade lignin
Curr. Opin. Chem. Biol. (2020)

E. Dfaz et al.
Aerobic degradation of aromatic compounds
Curr. Opin. Biotechnol. (2013)

R.W. Erb et al.

Characterization of a gene cluster from Ralstonia eutropha JMP134 encoding metabolism of 4-
methylmuconolactone
Gene (1998)

M.E. Guazzaroni et al.

The multidrug efflux regulator TtgV recognizes a wide range of structurally different effectors in solution
and complexed with target DNA: evidence from isothermal titration calorimetry
J. Biol. Chem. (2005)
6/3/24,14:18 Bacterial membrane transporter systems for aromatic compounds: Regulation, engineering, and biotechnological applications - S...

H. Hong et al.
The outer membrane protein OmpW forms an eight-stranded 0-barrel with a hydrophobic channel
J. Biol. Chem. (2006)

K. L. Howdeshell et al.
Mechanisms of action of phthalate esters, individually and in combination, to induce abnormal reproductive
development in male laboratory rats
Environ. Res. (2008)

https://www.sciencedirect.com/science/article/abs/pii/S0734975022000489 5/6
 xz View more references

Cited by (0)

View full text

© 2022 Elsevier Inc. All rights reserved.

ELSEVIER

All content on this site: Copyright © 2024 Elsevier B.V., its licensors, and contributors. All rights are reserved, including those for text and data mining, Al training, and similar
technologies. For all open access content, the Creative Commons licensing terms apply.

GLRELX™

https://www.sciencedirect.com/science/article/abs/pii/S0734975022000489 6/6