Recent advances in biosynthesis of chemicals by microbial co-culture

LI Xianglai; SHEN Xiaolin; WANG Jia; YUAN Qipeng; SUN Xinxiao

doi:10.12211/2096-8280.2020-053

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Recent advances in biosynthesis of chemicals by microbial co-culture

Invited Review | 更新时间：2025-03-20

- Recent advances in biosynthesis of chemicals by microbial co-culture
- Synthetic Biology Journal Vol. 2, Issue 6, Pages: 876-885(2021)
- 作者机构：
  
  北京化工大学，化工资源有效利用国家重点实验室，北京 100029
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2020-053
  CLC： Q812
- Received：18 April 2020，
  
  Revised：2021-01-15，
  
  Published：31 December 2021
- 稿件说明：
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李向来，申晓林，王佳，袁其朋，孙新晓. 微生物共培养生产化学品的研究进展［J］. 合成生物学， 2021， 2（6）： 876-885

LI Xianglai， SHEN Xiaolin， WANG Jia， YUAN Qipeng， SUN Xinxiao. Recent advances in biosynthesis of chemicals by microbial co-culture［J］. Synthetic Biology Journal， 2021， 2（6）： 876-885
李向来，申晓林，王佳，袁其朋，孙新晓. 微生物共培养生产化学品的研究进展［J］. 合成生物学， 2021， 2（6）： 876-885 DOI： 10.12211/2096-8280.2020-053.

LI Xianglai， SHEN Xiaolin， WANG Jia， YUAN Qipeng， SUN Xinxiao. Recent advances in biosynthesis of chemicals by microbial co-culture［J］. Synthetic Biology Journal， 2021， 2（6）： 876-885 DOI： 10.12211/2096-8280.2020-053.

摘要

生物合成已成为化学品绿色制造的重要方式。传统上，微生物合成化学品以单菌株培养为主。然而，单培养经常存在引入复杂途径造成沉重代谢负担、细胞微环境无法满足所有酶的功能性表达以及不同途径模块之间相互干扰等问题。借鉴自然界中普遍存在的共生现象，研究者开发了共培养技术，通过在同一体系中培养两种或多种细胞，以充分模拟自然共生环境，实现不同物种之间能量、物质及信号的交流，达到劳动分工以及代谢分区的目的。该技术在减轻宿主代谢负担、提供适宜的酶催化环境以及底物共利用方面表现出突出优势。不过作为一种新兴技术，微生物共培养技术在菌群稳定性、物种兼容性以及菌群比例调控等方面还存在一些挑战。本文列举了近年来微生物共培养划分长途径减轻代谢负担以及利用复杂、混合、非常规底物生产化学品和扩大化学品多样性的成功案例，总结了通过群体感应调控菌群比例以及通过计算机模拟工具预测菌群动态变化的研究进展，并对设计复杂稳定可控的共培养体系在高效生产化学品方面的应用前景和挑战进行了讨论。共培养技术有望成为合成复杂化学品的重要策略，并推动合成生物学的发展。

Abstract

Biosynthesis has become an important way of green manufacturing of chemicals. Traditionally

microbial synthesis of chemicals mainly uses a single strain. However

mono-culture often has the following problems:(1) Introduction of complex pathways causes heavy metabolic burden

(2) the cell microenvironment cannot fulfil the functional expression of all enzymes in the pathways

and (3) the mutual interference between modules of different pathways. Inspired by the natural symbiosis

researchers have developed co-culture technology. By cultivating two or more different cells in the same system

they can fully simulate the natural symbiosis environment

realizing the exchange of energy

materials and signals between different species and achieving the purpose of division of labor and metabolic compartmentation. This technology shows outstanding advantages in reduction of the metabolic burden and provision of suitable environment for different enzymes. Co-culture strategy can also be applied in the aspect of utilizing complex (

e.g.

lignocellulose)

mixed (

e.g.

glucose/xylose/arabinose) or nonconventional (methane

CO and CO

) carbon sources. Synthesis of the target products competes with the nati

ve metabolism for precursors

energy and other resources. Introduction of long pathways in a single strain may cause severe metabolic burden. Splitting and distributing pathways to different cells can alleviate such burden. In addition

each module can be optimized independently

and the balance between the modules can be achieved by adjusting the proportion of strains. Studies have shown that co-culture can significantly affect microbial metabolism and activate silent biosynthetic pathways. In recent years

hundreds of new compounds including polyketones

macrolides and diterpenes have been discovered through co-culture techniques. As an emerging technology

microbial co-culture still has many challenges in the prediction and control of the proportion of different strains. This review lists recent successful cases of microbial co-culture to produce chemicals

summarizes the research progress on regulating the strain proportion through quorum sensing and predicting the dynamic changes through computer simulation tools. Finally

the prospects and challenges in this emerging technology is also discussed.

关键词

Keywords

references

SUN X X , SHEN X L , JAIN R , et al . Synthesis of chemicals by metabolic engineering of microbes [J ] . Chemical Society Reviews , 2015 , 44 ( 11 ): 3760 - 3785 .

DE LIMA BROSSI M J , JIMÉNEZ D J , CORTES-TOLALPA L , et al . Soil-derived microbial consortia enriched with different plant biomass reveal distinct players acting in lignocellulose degradation [J ] . Microbial Ecology , 2016 , 71 ( 3 ): 616 - 627 .

BILIOURIS K , BABSON D , SCHMIDT-DANNERT C , et al . Stochastic simulations of a synthetic bacteria-yeast ecosystem [J ] . BMC Systems Biology , 2012 , 6 : 58 .

ZHOU K , QIAO K J , EDGAR S , et al . Distributing a metabolic pathway among a microbial consortium enhances production of natural products [J ] . Nature Biotechnology , 2015 , 33 ( 4 ): 377 - 383 .

HANLY T J , HENSON M A . Dynamic flux balance modeling of microbial co-cultures for efficient batch fermentation of glucose and xylose mixtures [J ] . Biotechnology and Bioengineering , 2011 , 108 ( 2 ): 376 - 385 .

WANG Z Y , CAO G L , ZHENG J , et al . Developing a mesophilic co-culture for direct conversion of cellulose to butanol in consolidated bioprocess [J ] . Biotechnology for Biofuels , 2015 , 8 ( 1 ): 84 .

SCHOLZ S A , GRAVES I , MINTY J J , et al . Production of cellulosic organic acids via synthetic fungal consortia [J ] . Biotechnology and Bioengineering , 2018 , 115 ( 4 ): 1096 - 1100 .

JIANG Y J , ZHANG T , LU J S , et al . Microbial co-culturing systems: butanol production from organic wastes through consolidated bioprocessing [J ] . Applied Microbiology and Biotechnology , 2018 , 102 ( 13 ): 5419 - 5425 .

JIANG Y J , GUO D , LU J S , et al . Consolidated bioprocessing of butanol production from xylan by a thermophilic and butanologenic Thermoanaerobacterium sp. M5 [J ] . Biotechnology for Biofuels , 2018 , 11 : 89 .

ROELL G W , ZHA J , CARR R R , et al . Engineering microbial consortia by division of labor [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 1 - 11 .

ZHANG H R , WANG X N . Modular co-culture engineering, a new approach for metabolic engineering [J ] . Metabolic Engineering , 2016 , 37 : 114 - 121 .

JONES J A , VERNACCHIO V R , SINKOE A L , et al . Experimental and computational optimization of an Escherichia coli co-culture for the efficient production of flavonoids [J ] . Metabolic Engineering , 2016 , 35 : 55 - 63 .

LI Z H , WANG X N , ZHANG H R . Balancing the non-linear rosmarinic acid biosynthetic pathway by modular co-culture engineering [J ] . Metabolic Engineering , 2019 , 54 : 1 - 11 .

LIU X , LI X B , JIANG J , et al . Convergent engineering of syntrophic Escherichia coli coculture for efficient production of glycosides [J ] . Metabolic Engineering , 2018 , 47 : 243 - 253 .

CHEN Z Y , SUN X X , LI Y , et al . Metabolic engineering of Escherichia coli for microbial synthesis of monolignols [J ] . Metabolic Engineering , 2017 , 39 : 102 - 109 .

ZHANG H R , PEREIRA B , LI Z J , et al . Engineering Escherichia coli coculture systems for the production of biochemical products [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2015 , 112 ( 27 ): 8266 - 8271 .

GUO X Y , LI Z H , WANG X N , et al . De novo phenol bioproduction from glucose using biosensor-assisted microbial coculture engineering [J ] . Biotechnology and Bioengineering , 2019 , 116 ( 12 ): 3349 - 3359 .

GANESAN V , LI Z H , WANG X N , et al . Heterologous biosynthesis of natural product naringenin by co-culture engineering [J ] . Synthetic and Systems Biotechnology , 2017 , 2 ( 3 ): 236 - 242 .

THUAN N H , TRUNG N T , CUONG N X , et al . Escherichia coli modular coculture system for resveratrol glucosides production [J ] . World Journal of Microbiology and Biotechnology , 2018 , 34 ( 6 ): 1 - 13 .

THUAN N H , CHAUDHARY A K , CUONG D V , et al . Engineering co-culture system for production of apigetrin in Escherichia coli [J ] . Journal of Industrial Microbiology & Biotechnology , 2018 , 45 ( 3 ): 175 - 185 .

CAMACHO-ZARAGOZA J M , HERNÁNDEZ-CHÁVEZ G , MORENO-AVITIA F , et al . Engineering of a microbial coculture of Escherichia coli strains for the biosynthesis of resveratrol [J ] . Microbial Cell Factories , 2016 , 15 ( 1 ): 1 - 11 .

AKDEMIR H , SILVA A , ZHA J , et al . Production of pyranoanthocyanins using Escherichia coli co-cultures [J ] . Metabolic Engineering , 2019 , 55 : 290 - 298 .

SUN J , RAZA M , SUN X X , et al . Biosynthesis of adipic acid via microaerobic hydrogenation of cis , cis -muconic acid by oxygen-sensitive enoate reductase [J ] . Journal of Biotechnology , 2018 , 280 : 49 - 54 .

FAN L H , ZHANG Z J , YU X Y , et al . Self-surface assembly of cellulosomes with two miniscaffoldins on Saccharomyces cerevisiae for cellulosic ethanol production [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2012 , 109 ( 33 ): 13260 - 13265 .

HE Q , HEMME C L , JIANG H L , et al . Mechanisms of enhanced cellulosic bioethanol fermentation by co-cultivation of Clostridium and Thermoanaerobacter spp .[J ] . Bioresource Technology , 2011 , 102 ( 20 ): 9586 - 9592 .

NAKAYAMA S , KIYOSHI K , KADOKURA T , et al . Butanol production from crystalline cellulose by cocultured Clostridium thermocellum and Clostridium saccharoperbutylacetonicum N1-4 [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 18 ): 6470 - 6475 .

MINTY J J , SINGER M E , SCHOLZ S A , et al . Design and characterization of synthetic fungal-bacterial consortia for direct production of isobutanol from cellulosic biomass [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2013 , 110 ( 36 ): 14592 - 14597 .

WANG M , YU C Z , ZHAO H M . Directed evolution of xylose specific transporters to facilitate glucose-xylose co-utilization [J ] . Biotechnology and Bioengineering , 2016 , 113 ( 3 ): 484 - 491 .

SEDLAK M , HO N W . Characterization of the effectiveness of hexose transporters for transporting xylose during glucose and xylose co-fermentation by a recombinant Saccharomyces yeast [J ] . Yeast , 2004 , 21 ( 8 ): 671 - 684 .

LI H B , SCHMITZ O , ALPER H S . Enabling glucose/xylose co-transport in yeast through the directed evolution of a sugar transporter [J ] . Applied Microbiology and Biotechnology , 2016 , 100 ( 23 ): 10215 - 10223 .

VERHOEVEN M D , DE VALK S C , DARAN J M G , et al . Fermentation of glucose-xylose-arabinose mixtures by a synthetic consortium of single-sugar-fermenting Saccharomyces cerevisiae strains [J ] . FEMS Yeast Research , 2018 , 18 ( 8 ): foy075 .

HILL E A , CHRISLER W B , BELIAEV A S , et al . A flexible microbial co-culture platform for simultaneous utilization of methane and carbon dioxide from gas feedstocks [J ] . Bioresource Technology , 2017 , 228 : 250 - 256 .

LEE C R , KIM C , SONG Y E , et al . Co-culture-based biological carbon monoxide conversion by Citrobacter amalonaticus Y19 and Sporomusa ovata via a reducing-equivalent transfer mediator [J ] . Bioresource Technology , 2018 , 259 : 128 - 135 .

WEISS T L , YOUNG E J , DUCAT D C . A synthetic, light-driven consortium of cyanobacteria and heterotrophic bacteria enables stable polyhydroxybutyrate production [J ] . Metabolic Engineering , 2017 , 44 : 236 - 245 .

DUCAT D C , AVELAR-RIVAS J A , WAY J C , et al . Rerouting carbon flux to enhance photosynthetic productivity [J ] . Applied and Environmental Microbiology , 2012 , 78 ( 8 ): 2660 - 2668 .

SMITH M J , FRANCIS M B . A designed A. vinelandii-S. elongatus coculture for chemical photoproduction from air, water, phosphate, and trace metals [J ] . ACS Synthetic Biology , 2016 , 5 ( 9 ): 955 - 961 .

HAYS S G , YAN L L W , SILVER P A , et al . Synthetic photosynthetic consortia define interactions leading to robustness and photoproduction [J ] . Journal of Biological Engineering , 2017 , 11 : 4 .

LI T , LI C-T , BUTLER K , et al . Mimicking lichens: incorporation of yeast strains together with sucrose-secreting cyanobacteria improves survival, growth, ROS removal, and lipid production in a stable mutualistic co-culture production platform [J ] . Biotechnology for Biofuels , 2017 , 10 ( 1 ): 55 .

LI T T , JIANG L Q , HU Y F , et al . Creating a synthetic lichen: mutualistic co -culture of fungi and extracellular polysaccharide-secreting cyanobacterium Nostoc PCC 7413 [J ] . Algal Research , 2020 , 45 : 101755 .

GOODWIN C R , COVINGTON B C , DEREWACZ D K , et al . Structuring microbial metabolic responses to multiplexed stimuli via self-organizing metabolomics maps [J ] . Chemistry & Biology , 2015 , 22 ( 5 ): 661 - 670 .

PONOMAROVA O , PATIL K R . Metabolic interactions in microbial communities: untangling the Gordian knot [J ] . Current Opinion in Microbiology , 2015 , 27 : 37 - 44 .

BERTRAND S , BOHNI N , SCHNEE S , et al . Metaboli te induction via microorganism co-culture: a potential way to enhance chemical diversity for drug discovery [J ] . Biotechnology Advances , 2014 , 32 ( 6 ): 1180 - 1204 .

HARWANI D , BEGANI J , LAKHANI J . Co-cultivation strategies to induce de novo synthesis of novel chemical scaffolds from cryptic secondary metabolite gene clusters [M ] // GEHLOT P, SINGH J. Fungi and their role in sustainable development: current perspectives . Springer , 2018 : 617 - 631 .

TAN Z Q , LEOW H Y , LEE D C W , et al . Co-culture systems for the production of secondary metabolites: current and future prospects [J ] . The Open Biotechnology Journal , 2019 , 13 ( 1 ): 18 - 26 .

MOUSSA M , EBRAHIM W , BONUS M , et al . Co-culture of the fungus Fusarium tricinctum with Streptomyces lividans induces production of cryptic naphthoquinone dimers [J ] . RSC Advances , 2019 , 9 ( 3 ): 1491 - 1500 .

MA Y J , ZHENG L P , WANG J W . Inducing perylenequinone production from a bambusicolous fungus Shiraia sp. S9 through co-culture with a fruiting body-associated bacterium Pseudomonas fulva SB 1 [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 121 .

HOSHINO S , WONG C P , OZEKI M , et al . Umezawamides, new bioactive polycyclic tetramate macrolactams isolated from a combined-culture of Umezawaea sp. and mycolic acid-containing bacterium [J ] . The Journal of Antibiotics , 2018 , 71 ( 7 ): 653 - 657 .

KHALIL Z G , CRUZ-MORALES P , LICONA-CASSANI C , et al . Inter-Kingdom beach warfare: microbial chemical communication activates natural chemical defences [J ] . The ISME Journal , 2019 , 13 ( 1 ): 147 - 158 .

ARORA D , CHASHOO G , SINGAMANENI V , et al . Bacillus amyloliquefaciens induces production of a novel blennolide K in coculture of Setophoma terrestris [J ] . Journal of Applied Microbiology , 2018 , 124 ( 3 ): 730 - 739 .

ZHOU Q Y , YANG X Q , ZHANG Z X , et al . New azaphilones and tremulane sesquiterpene from endophytic Nigrospora oryzae cocultured with Irpex lacteus [J ] . Fitoterapia , 2018 , 130 : 26 - 30 .

NG W L , BASSLER B L . Bacterial quorum-sensing network architectures [J ] . Annual Review of Genetics , 2009 , 43 : 197 - 222 .

DAVIS R M , MULLER R Y , HAYNES K A . Can the natural diversity of quorum-sensing advance synthetic biology? [J ] . Frontiers in Bioengineering and Biotechnology , 2015 , 3 : 30 .

KYLILIS N , TUZA Z A , STAN G B , et al . Tools for engineering coordinated system behaviour in synthetic microbial consortia [J ] . Nature Communications , 2018 , 9 ( 1 ): 2677 .

SCOTT S R , HASTY J . Quorum sensing communication modules for microbial consortia [J ] . ACS Synthetic Biology , 2016 , 5 ( 9 ): 969 - 977 .

CHEN Y , KIM J K , HIRNING A J , et al . Emergent genetic oscillations in a synthetic microbial consortium [J ] . Science , 2015 , 349 ( 6251 ): 986 - 989 .

SCOTT S R , DIN M O , BITTIHN P , et al . A stabilized microbial ecosystem of self-limiting bacteria using synthetic quorum-regulated lysis [J ] . Nature Microbiology , 2017 , 2 : 17083 .

MCCARDELL R D , HUANG S , GREEN L N , et al . Control of bacterial population density with population feedback and molecular sequestration [EB/OL ] . bioRxiv , 2017 , DOI: 10.1101/225045 http://dx.doi.org/10.1101/225045 .

THOMPSON J A , OLIVEIRA R A , DJUKOVIC A , et al . Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota [J ] . Cell Reports , 2015 , 10 ( 11 ): 1861 - 1871 .

STEPHENS K , POZO M , TSAO C Y , et al . Bacterial co-culture with cell signaling translator and growth controller modules for autonomously regulated culture composition [J ] . Nature Communications , 2019 , 10 ( 1 ): 4129 .

AUTEBERT J , COUDERT B , BIDARD F-C , et al . Microfluidic: an innovative tool for efficient cell sorting [J ] . Methods , 2012 , 57 ( 3 ): 297 - 307 .

KOCH S , BENNDORF D , FRONK K , et al . Predicting compositions of microbial communities from stoichiometric models with applications for the biogas process [J ] . Biotechnology for Biofuels , 2016 , 9 ( 1 ): 17 .

MILNE C B , KIM P J , EDDY J A , et al . Accomplishments in genome-scale in silico modeling for industrial and medical biotechnology [J ] . Biotechnology Journal , 2009 , 4 ( 12 ): 1653 - 1670 .

MILLER I J , VANEE N , FONG S S , et al . Lack of overt genome reduction in the bryostatin-producing bryozoan symbiont ''candidatus endobugula sertula'' [J ] . Applied and Environmental Microbiology , 2016 , 82 ( 22 ): 6573 - 6583 .

STOLYAR S , VAN DIEN S , HILLESLAND K L , et al . Metabolic modeling of a mutualistic microbial community [J ] . Molecular System Biology , 2007 , 3 ( 1 ): 92 .

SALIMI F , ZHUANG K , MAHADEVAN R . Genome‐scale metabolic modeling of a clostridial co‐culture for consolidated bioprocessing [J ] . Biotechnology Journal , 2010 , 5 ( 7 ): 726 - 738 .

KONG W , MELDGIN D R , COLLINS J J , et al . Designing microbial consortia with defined social interactions [J ] . Nature Chemical Biology , 2018 , 14 ( 8 ): 821 - 829 .

MCCULLY A L , LASARRE B , MCKINLAY J B . Growth-independent cross-feeding modifies boundaries for coexistence in a bacterial mutualism [J ] . Environmental Microbiology , 2017 , 19 ( 9 ): 3538 - 3550 .

TSOI R , WU F L , ZHANG C , et al . Metabolic division of labor in microbial systems [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2018 , 115 ( 10 ): 2526 - 2531 .

GUERRA-BUBB J , CROTEAU R , WILLIAMS R M . The early stages of taxol biosynthesis: an interim report on the synthesis and identification of early pathway metabolites [J ] . Natural Product Reports , 2012 , 29 ( 6 ): 683 - 696 .

NITSCHKE M , PASTORE G M . Production and properties of a surfactant obtained from Bacillus subtilis grown on cassava wastewater [J ] . Bioresource Technology , 2006 , 97 ( 2 ): 336 - 341 .

TAO K Y , LIU X Y , CHEN X P , et al . Biodegradation of crude oil by a defined co-culture of indigenous bacterial consortium and exogenous Bacillus subtilis [J ] . Bioresource Technology , 2017 , 224 : 327 - 332 .

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