微生物学报

Pathway	Representative microorganisms	Core enzymes and key characteristics	Advantages	Bottlenecks	Roles in synthetic consortia
Calvin-Benson-Bassham (CBB) cycle	Cyanobacteria, plants, some chemolithoautotrophs	RuBisCO; 3-phosphoglycerate as the primary product	Most thoroughly characterized; natively coupled with photosynthesis; compatible with light-driven systems	Low catalytic efficiency of RuBisCO; photorespiration carbon loss; light transfer limitations	Carbon-fixing module for saccharides/organic acids^[6,13]
Wood-Ljungdahl (WL) pathway	Acetogens, Clostridia, methanogenic archaea	Acetyl-CoA synthase; CO₂ converted directly to acetyl-CoA	Highest energy efficiency; compatible with syngas (CO/CO₂/H₂)	Strict anaerobic requirement; poor gas-liquid mass transfer; pH sensitivity; slow growth	Gas carbon-fixing module, acetate/ethanol supplying module^[14-15]
rTCA cycle and other native or synthetic carbon fixation pathways	Anaerobic/microaerophilic bacteria, archaea, engineered strains	ATP citrate lyase; 2-oxoglutarate synthase	High energy efficiency; short metabolic routes; diverse target products	Oxygen sensitivity; low heterologous expression efficiency of key enzymes; difficult engineering manipulation	High-specificity carbon-fixing module; chassis for synthetic pathways^[16-18]
Hydrogen-oxidizing autotrophic carbon fixation system (with CBB as carbon fixation pathway)	Cupriavidus necator and related strains	Hydrogenase; H₂ serves as electron donor	Electro-hydrogen-biological coupling; no light limitation; fast growth; capable of PHA biosynthesis	Safety hazards of H₂/O₂ mixture; strict gas proportion control; weak product secretion capacity	Electrogenic carbon-fixing module; carbon intermediate supplying module^[19-20]

Pathway	Representative microorganisms	Core enzymes and key characteristics	Advantages	Bottlenecks	Roles in synthetic consortia
Calvin-Benson-Bassham (CBB) cycle	Cyanobacteria, plants, some chemolithoautotrophs	RuBisCO; 3-phosphoglycerate as the primary product	Most thoroughly characterized; natively coupled with photosynthesis; compatible with light-driven systems	Low catalytic efficiency of RuBisCO; photorespiration carbon loss; light transfer limitations	Carbon-fixing module for saccharides/organic acids^[6,13]
Wood-Ljungdahl (WL) pathway	Acetogens, Clostridia, methanogenic archaea	Acetyl-CoA synthase; CO₂ converted directly to acetyl-CoA	Highest energy efficiency; compatible with syngas (CO/CO₂/H₂)	Strict anaerobic requirement; poor gas-liquid mass transfer; pH sensitivity; slow growth	Gas carbon-fixing module, acetate/ethanol supplying module^[14-15]
rTCA cycle and other native or synthetic carbon fixation pathways	Anaerobic/microaerophilic bacteria, archaea, engineered strains	ATP citrate lyase; 2-oxoglutarate synthase	High energy efficiency; short metabolic routes; diverse target products	Oxygen sensitivity; low heterologous expression efficiency of key enzymes; difficult engineering manipulation	High-specificity carbon-fixing module; chassis for synthetic pathways^[16-18]
Hydrogen-oxidizing autotrophic carbon fixation system (with CBB as carbon fixation pathway)	Cupriavidus necator and related strains	Hydrogenase; H₂ serves as electron donor	Electro-hydrogen-biological coupling; no light limitation; fast growth; capable of PHA biosynthesis	Safety hazards of H₂/O₂ mixture; strict gas proportion control; weak product secretion capacity	Electrogenic carbon-fixing module; carbon intermediate supplying module^[19-20]

Carbon fixation module	Downstream module	Forms of carbon sources	Target products	Cooperation mechanism	Main advantages	Key challenges
SynechococcuscscB	Pseudomonas putidacscAB	Sucrose	Polyhydroxyalkanoates (PHA)	Commensalism: cyanobacteria conduct photosynthetic carbon fixation and secrete sucrose, while Pseudomonas sp. utilizes sucrose to synthesize polyhydroxyalkanoate (PHA)	Platformized and scalable	Carbon flux competition^[45]
Synechococcus elongatus UTEX 2973	E. coli BL21 (DE3)	Sucrose	3-hydroxypropionic acid (3-HP)	Mutualistic symbiosis: cyanobacteria fix carbon via photosynthesis and secrete sucrose, while Escherichia coli utilizes sucrose to synthesize 3-HP and eliminate reactive oxygen species (ROS)	The growth of cyanobacteria was markedly improved	Dynamic control of microbial community ratios^[46]
Synechococcus elongatus PCC79429 (cscB)	E. coli BL21 (efe, ispS)	Sucrose	Ethylene, isoprene	Commensalism (cyanobacteria secrete sugars and oxygen, while Escherichia coli utilizes sucrose to synthesize ethylene and isoprene)	Light-driven, short integrated metabolic pathway	Limited sucrose flux, photoinhibition^[47]
Clostridium acetobutylicum	Clostridium kluyveri	CO/CO₂→acetic acid	Butanol, hexanol	Mutualistic symbiosis: Clostridium ljungdahlii consumes and detoxifies CO while supplying acetate and ethanol; Clostridium kluyveri utilizes these substrates to elongate carbon chains and synthesize medium-chain fatty acids and higher alcohols	Carbon chain elongation with high carbon yields	pH control^[48]
Engineered Clostridium acetobutylicum	Clostridium ljungdahlii	Sugars+CO₂	Isopropanol, butanol	Mutualistic symbiosis: Clostridium acetobutylicum produces CO₂, H₂, and acetone; Clostridium ljungdahlii fixes carbon, converts acetone to isopropanol, and generates acetate to feed back to the primary strain	Enhance carbon utilization efficiency	Maintain community stability^[16]
Acetobacterium	Alcaligenes	CO₂+electricity (electrolytic H₂ generation)	Single cell protein (SCP)	Mutualistic symbiosis: Acetobacter produces acetate to feed Alcaligenes, while Alcaligenes consumes acetate to relieve metabolic inhibition and balance the pH of the system	Alleviated product inhibition, low wastewater generation, nearly 100% gas utilization efficiency, high protein content	Low electron-to-protein conversion efficiency and high risk of membrane fouling during long-term operation^[49]
Cupriavidus necator	Escherichia coli, Saccharomyces cerevisiae	CO₂+H₂	PHA/other chemicals	Cupriavidus performs chemolithoautotrophic carbon fixation and secretes sucrose to support heterotrophs; heterotrophs consume sucrose to relieve product inhibition and drive upstream biosynthesis	High cell density, industrial potential	Cases of co-cultivation remain scarce^[50]

Carbon fixation module	Downstream module	Forms of carbon sources	Target products	Cooperation mechanism	Main advantages	Key challenges
SynechococcuscscB	Pseudomonas putidacscAB	Sucrose	Polyhydroxyalkanoates (PHA)	Commensalism: cyanobacteria conduct photosynthetic carbon fixation and secrete sucrose, while Pseudomonas sp. utilizes sucrose to synthesize polyhydroxyalkanoate (PHA)	Platformized and scalable	Carbon flux competition^[45]
Synechococcus elongatus UTEX 2973	E. coli BL21 (DE3)	Sucrose	3-hydroxypropionic acid (3-HP)	Mutualistic symbiosis: cyanobacteria fix carbon via photosynthesis and secrete sucrose, while Escherichia coli utilizes sucrose to synthesize 3-HP and eliminate reactive oxygen species (ROS)	The growth of cyanobacteria was markedly improved	Dynamic control of microbial community ratios^[46]
Synechococcus elongatus PCC79429 (cscB)	E. coli BL21 (efe, ispS)	Sucrose	Ethylene, isoprene	Commensalism (cyanobacteria secrete sugars and oxygen, while Escherichia coli utilizes sucrose to synthesize ethylene and isoprene)	Light-driven, short integrated metabolic pathway	Limited sucrose flux, photoinhibition^[47]
Clostridium acetobutylicum	Clostridium kluyveri	CO/CO₂→acetic acid	Butanol, hexanol	Mutualistic symbiosis: Clostridium ljungdahlii consumes and detoxifies CO while supplying acetate and ethanol; Clostridium kluyveri utilizes these substrates to elongate carbon chains and synthesize medium-chain fatty acids and higher alcohols	Carbon chain elongation with high carbon yields	pH control^[48]
Engineered Clostridium acetobutylicum	Clostridium ljungdahlii	Sugars+CO₂	Isopropanol, butanol	Mutualistic symbiosis: Clostridium acetobutylicum produces CO₂, H₂, and acetone; Clostridium ljungdahlii fixes carbon, converts acetone to isopropanol, and generates acetate to feed back to the primary strain	Enhance carbon utilization efficiency	Maintain community stability^[16]
Acetobacterium	Alcaligenes	CO₂+electricity (electrolytic H₂ generation)	Single cell protein (SCP)	Mutualistic symbiosis: Acetobacter produces acetate to feed Alcaligenes, while Alcaligenes consumes acetate to relieve metabolic inhibition and balance the pH of the system	Alleviated product inhibition, low wastewater generation, nearly 100% gas utilization efficiency, high protein content	Low electron-to-protein conversion efficiency and high risk of membrane fouling during long-term operation^[49]
Cupriavidus necator	Escherichia coli, Saccharomyces cerevisiae	CO₂+H₂	PHA/other chemicals	Cupriavidus performs chemolithoautotrophic carbon fixation and secretes sucrose to support heterotrophs; heterotrophs consume sucrose to relieve product inhibition and drive upstream biosynthesis	High cell density, industrial potential	Cases of co-cultivation remain scarce^[50]

合成微生物群落驱动的二氧化碳固定转化体系设计与构建

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赵维 ¹^,³ , 成婷婷 ¹ , 柴清圆 ¹^,² , 班美玲 ¹ , 董继焕 ¹^,² , 黄志勇 ¹^,³ , 韩一凡 ¹^,³^,^*

微生物学报 | 综述 2026,66(9): 4456-4470

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微生物学报 |综述 2026 , 66 (9) : 4456 -4470

合成微生物群落驱动的二氧化碳固定转化体系设计与构建

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赵维¹^,³, 成婷婷¹, 柴清圆¹^,², 班美玲¹, 董继焕¹^,², 黄志勇¹^,³, 韩一凡¹^,³^,^*

作者信息

^1.中国科学院天津工业生物技术研究所，天津市工业生物系统与过程工程重点实验室，天津

^2.天津科技大学生物工程学院，天津

^3.合成生物国家技术创新中心，天津

通讯作者:

韩一凡

作者简介:

作者贡献声明

赵维：文章主要内容的组织撰写与修改，案例搜集、整理；成婷婷：文章内容的修改，案例搜集整理；柴清圆：调查研究；班美玲：可视化呈现；董继焕：文章参考文献整理；黄志勇：统筹安排，逻辑思路指导，基金支持；韩一凡：文章主题和框架制定，文章修改，基金支持。

Design and construction of carbon dioxide fixation and transformation systems driven by synthetic microbial consortia

Wei ZHAO¹^,³, Tingting CHENG¹, Qingyuan CHAI¹^,², Meiling BAN¹, Jihuan DONG¹^,², Zhiyong HUANG¹^,³, Yifan HAN¹^,³^,^*

Affiliations

^1.Tianjin Key Laboratory of Industrial Biological Systems and Process Engineering, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China

^2.College of Biotechnology, Tianjin University of Science and Technology, Tianjin, China

^3.National Technology Innovation Center for Synthetic Biology, Tianjin, China

Corresponding Author:

^*E-mail: han_yf@tib.cas.cn

出版时间: 2026-09-04 doi: 10.13343/j.cnki.wsxb.20260431

文章导航

摘要

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随着“碳中和”目标的提出，利用微生物将二氧化碳(CO₂)转化为高附加值化学品、燃料及生物材料已成为清洁能源与绿色化工领域的重要发展方向。单一菌株的碳转化体系虽具备较好的可控性，但实际应用中仍面临代谢负荷过重、固碳通量受限、能量与还原力供给不足、产物得率偏低及工艺放大困难等多重挑战。相比之下，合成微生物群落可通过理性设计不同功能微生物的组合，实现代谢分工、分担代谢负担、提升固碳效率、增加产物多样性，进而提升产物价值，推动CO₂固定技术的工业化落地。本文综述了当前合成微生物群落在CO₂转化体系中的应用进展，涵盖以固碳模块划分的光能驱动系统、氢能驱动系统，以及具备更高应用安全性的潜在化能系统；总结了基于合成微生物群落构建碳循环体系的核心设计原则，梳理了当前领域面临的关键挑战与未来发展方向，可为构建高效稳定的人工碳循环系统提供理论与实践参考。

关键词

合成微生物群落 / CO₂转化 / 功能分工 / 代谢互馈 / 碳固定

Abstract

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With the proposal of carbon neutrality goals, microbial conversion of CO₂ into high-value chemicals, fuels, and biomaterials has emerged as an important strategy for clean energy and green manufacturing. Although single-strain carbon fixation systems have ideal controllability, they still face limitations, including heavy metabolic burden, limited carbon fixation flux, insufficient energy and reducing power supply, low yield, and challenges in industrial-scale application. In contrast, synthetic microbial consortia enable rational metabolic division of labor among functionally distinct microorganisms, thereby alleviating metabolic burden, enhancing carbon fixation efficiency, and expanding product diversity. These advantages further improve product value and promote the industrial application of CO₂ fixation. This review summarizes recent advances in the application of synthetic microbial consortia for CO₂ conversion, including photosynthesis-driven systems, hydrogen-driven systems, and potentially safer chemoautotrophic systems classified according to carbon fixation modules. In addition, this paper discusses the design principles for constructing carbon cycling systems based on synthetic microbial consortia, together with current challenges and future perspectives, providing theoretical and practical guidance for the development of efficient and stable artificial carbon cycling systems.

Key words

synthetic microbial consortium / CO₂ conversion / functional division of labor / metabolic cross-feeding / carbon fixation

引用本文

赵维, 成婷婷, 柴清圆, 班美玲, 董继焕, 黄志勇, 韩一凡. 合成微生物群落驱动的二氧化碳固定转化体系设计与构建. 微生物学报, 2026 , 66 (9) : 4456 -4470 . DOI: 10.13343/j.cnki.wsxb.20260431

Wei ZHAO, Tingting CHENG, Qingyuan CHAI, Meiling BAN, Jihuan DONG, Zhiyong HUANG, Yifan HAN. Design and construction of carbon dioxide fixation and transformation systems driven by synthetic microbial consortia[J]. Acta Microbiologica Sinica, 2026 , 66 (9) : 4456 -4470 . DOI: 10.13343/j.cnki.wsxb.20260431

正文

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CO₂是人类活动排放的主要温室气体之一，其在大气中的持续累积被认为是导致全球变暖和气候变化的重要驱动因素。开发高效、可持续的CO₂生物转化技术是促进碳资源循环利用、缓解气候变化并实现“双碳”目标的重要策略^[1-2]。自然界中广泛分布着能够将CO₂同化为有机物的微生物。目前，基于单一菌株的固碳体系仍是CO₂生物转化研究的重要方向，然而单一微生物固碳体系通常需要在碳固定、能量供给和产物合成之间进行权衡，极易出现代谢负担过重、碳转化效率受限及产物谱较窄等问题，构建分工协作的微生物群落是解决这一问题的重要途径之一^[3-4]。通过设计人工合成微生物群落可实现物种间代谢分工与生态互作，获得更稳定、环境适应性更强的生物固碳转化体系，提升碳固定效率，扩展生物固碳转化的产物谱，促进以CO₂为原料的产业经济发展。

微生物群落是具有明确分类学与功能特征的菌群组合，在特定条件下实现可预测的功能输出。合成微生物群落的人工设计与构建遵循四大核心准则：功能简约化与模块化、互作网络可预测与可控化、高稳健稳定群落的定向构建，以及基于精简思路搭建最小功能可行菌群^[5]。在合成微生物群落中将不同的功能模块赋能于独立的物种，通过种间互作，采用“自上而下”或“自下而上”的策略进行物种组装，实现特定功能^[6]。对应CO₂转化与固定体系，可根据碳的输入和产物的生成分为固碳模块和产物模块^[7-8]。固碳模块一般采用自养型微生物作为底盘细胞，依据固碳途径与底物利用特性的差异，主要包括2类：一类是利用Calvin-Benson-Bassham (CBB)循环的光能及化能自养微生物，适用于广泛的CO₂转化场景；另一类是依托Wood-Ljungdahl (WL)途径的C1气体发酵微生物(多为化能自养型)，擅长利用CO₂/H₂或合成气进行高效转化^[7]。产物模块一般选用可利用固碳模块的产物进行生长和生产的异养型微生物作为底盘细胞，在产物模块选择合适的异养协作菌株是获得高效、高产体系的关键，理想的异养协作菌株需要满足快速高效利用中间产物生长，且具有稳定的产物生产速率及对中间产物耐受范围广等要求，例如经过代谢工程改造的大肠埃希氏菌(Escherichia coli)、酵母菌等^[7-8]。

由于自养菌株与异养菌株在生长特性及环境需求上存在固有差异，模块化的合成微生物群落通过优化菌群结构，在维持单一菌株功能稳定性的基础上有效提升了系统的整体代谢效率，并增强了群落组合的可控性，为技术的落地应用提供了可能^[8]。尽管合成微生物群落在CO₂转化体系中具有较大的应用潜力，但微生物互作关系的复杂性导致功能菌株选择、互作网络预测、群落稳定性等方面依然面临较大困难^[9-10]。除此之外，固碳途径效率较低，中间碳流供给不足，以异养菌株为产物模块的代谢途径复杂，目标产物浓度低等问题也进一步限制了合成微生物菌群在CO₂转化方面的工业化应用^[11-12]。因此在已有研究实例中总结通用的构建原则，筛选高契合度的协作菌株，探索高效低成本的合成策略，提升合成微生物群落的固碳效率和产物合成效率仍是当前的重点研究方向。

本文在总结合成微生物群落基本概念的基础上，重点介绍了合成微生物群落中的核心CO₂固定途径，系统梳理了碳循环体系构建中的设计原则及协同代谢机制，列举了典型应用案例并展望未来发展方向，阐述了提升碳固定与转化效率的合成微生物群落构建策略，为合成微生物在CO₂转化体系中的高质量应用提供参考。

1 合成微生物群落中的CO₂固定途径

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目前研究较为深入的CO₂微生物固定途径主要可归纳为4类：以CBB循环为代表的光能自养途径、WL途径、还原三羧酸(tricarboxylic acid cycle, rTCA)循环及其他天然或人工固碳路径，以及较为特殊的氢氧化自养体系。CBB循环是光合自养微生物的经典固碳通路，与光驱动系统天然适配，但受限于核酮糖-1,5-二磷酸羧化酶/加氧酶(ribulose bisphosphate carboxylase oxygenase, RuBisCO)催化效率低、光呼吸损耗大、光传递限制、产物生成效率低等问题，现有提升碳固定效率的手段多为引入外源途径或改造现有天然代谢途径，延伸并拓展光合细菌的碳流分布^[13-14]。WL途径能量转化效率最高，可直接转化CO/CO₂和H₂合成小分子有机酸和醇等中间产物，是合成气发酵与厌氧固碳的核心模块，但存在产物反馈抑制、胞内乙酸胁迫、产物碳链延伸能量成本高的不足，无法独立实现复杂产物的合成^[15-16]。还原三羧酸循环及其他天然或人工固碳路径能量效率高，但普遍存在氧敏感特性，关键酶多来源于远缘厌氧微生物，在常用工程宿主中异源表达难度大，且途径重构与调控整合的技术门槛较高^[17]；基于多酶体系构建的人工固碳途径虽具备较高应用潜力，但目前仍缺乏稳定高效的生物元件与标准化组装策略，制约了其实际落地应用^[18]。氢氧化自养固碳体系也以CBB循环为核心固碳途径，可耦合“电-氢-生物转化”过程，不受光照限制、菌株生长速率快，但H₂/O₂混合气安全风险高，气体比例调控与反应器设计要求严苛，且自养代谢通量、还原力供给及产物合成效率仍存在明显短板^[19-20]。几类途径的优缺点对比总结在表1中，总体而言，各类固碳途径均需针对性地突破关键技术瓶颈，才可在合成群落中实现高效、稳定、可放大的碳循环与产物合成。

综上所述，天然与人工固碳途径虽各具优势，但在构建高效合成群落时普遍面临热力学约束、关键酶异源适配性差及代谢网络刚性过强^[21]等多重瓶颈。特别是自养菌与异养菌在生长动力学与环境适应性上的巨大差异，使得单纯依靠自然进化的代谢网络难以实现稳定的跨物种物质与能量耦合。因此，基于上述不同固碳途径的生理生化特性，通过理性的工程化设计打破物种界限、重塑群落互作逻辑，并建立可控的群落组装与稳态维持机制，是实现CO₂向目标化学品高效转化的关键科学问题。下文将重点阐述合成群落构建的设计原则与调控策略。

2 基于合成微生物群落的碳循环体系设计原则

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基于对自然生态系统中菌株间协同互作机制的解析，指导合成微生物群落工程化重构，有望提升碳固定效率并实现产物多元化。在典型的自养-异养共培养体系中，二者通过中间代谢产物传递实现代谢耦合：自养微生物固定无机一碳碳源，将无机碳转化为有机碳，有机碳作为异养菌生长与产物合成的底物^[8]；相应地，异养微生物通过分泌关键生长因子、缓冲环境胁迫或优化微环境，反向促进自养微生物的生长代谢，从而构建起以物质交换、功能互补及生态协同为特征的碳固定与转化网络^[8,16](图1)。因此，这类合成微生物群落的关键构建策略，需要从碳源供给、环境互馈、代谢依赖、功能耦联、空间组织与过程控制等多维度考量，筛选能够建立稳定且可调控种间互作关系的功能菌株(图1)。

2.1 可供碳源设计：构建自养菌到异养菌的稳定碳传递通路

CO₂的生物固定过程消耗还原力和能量，且反应吉布斯自由能较高，微生物生长通常较为缓慢，难以兼顾固碳与产物合成，面临巨大代谢压力。通过构建合成群落实施模块化分工可有效实现代谢负荷的均衡分配与能量解耦^[22]。在该策略中，自养菌利用光能、氢能或化学能实现CO₂固定，维持菌体生长与简单代谢产物合成，而异养菌则利用自养菌的代谢产物作为底物，完成高能耗复杂产物的合成，从而提升系统的整体效率与产物覆盖范围^[8,16,23]。在自养-异养合成群落中，自养模块通过固定CO₂合成可被异养成员直接利用的代谢产物(如糖类、乙酸、乙醇、甲酸等)，为群落提供碳源与能量，是维持系统稳态与功能持续运行的关键驱动单元^[2,8,24-25]。这类中间产物需要兼具高分泌效率、低生物毒性、高生物利用度，且不扰动共培养体系稳定性。这一碳流传递过程是群落设计的关键限速步骤，若碳源供给受限或下游利用效率不足将导致菌群耦联松散、碳转化效率衰减，进而引发整个合成系统失稳。

2.2 生长因子与环境调节：构建异养菌对自养菌的反向支持

合成群落内的物质交换并非局限于单向碳源传递，自养菌与异养菌之间普遍存在复杂的双向互馈机制。异养菌在摄取碳源的过程中不仅能通过分泌维生素、氨基酸及辅因子等生长促进物质^[26]，还能通过清除抑制性代谢产物、调控氧化还原平衡及缓冲微环境波动，为自养菌营造适宜的生长条件^[27]。这种基于生长因子传递与环境重塑的协同互作，使群落内部关系由单向依赖演变为双向互利。相比单纯的碳源传递，这种双向环境互馈体系在提升群落稳健性、延长运行周期以及增强群落抵御外界环境扰动方面具有显著优势^[28]。最具代表性的是恺迪苏(Calysta)公司与安迪苏(Adisseo)合资企业Calysseo开发的FeedKind^®工艺，该工艺以荚膜甲基球菌(Methylococcus capsulatus)CICC 11106s为核心固碳菌株，辅以韩央大贪铜菌(Cupriavidus cauae) CICC 11107s、丹麦解硫胺素芽孢杆菌(Aneurinibacillus danicus) CICC 11108s和土壤短芽孢杆菌(Brevibacillus agri) CICC 11109s共培养，以天然气中甲烷为唯一碳源经连续发酵生产单细胞蛋白，已实现工业化应用^[29]。虽然该体系中菌株间的互作机制属于商业机密，未见公开原始文献，但学术界大量报道了甲烷氧化菌及其异养伴生微生物(卫星菌)之间的协同机制^[30]，如贪铜菌可高效降解乙酸、甲酸等发酵抑制物，同时兼具重金属抗性，适配复杂工业发酵环境^[31]；解硫胺素芽孢杆菌对发酵工况耐受性强，可协同清除体系内有害代谢产物^[32]；土壤短芽孢杆菌则利用菌体裂解物与小分子有机质参与营养循环，有效平衡菌群营养分配、缓解种间竞争，共同保障发酵系统长期稳定运行^[33]。目前CO₂固定体系中尚未见达到同等规模的类似案例。

2.3 代谢依赖锁定：通过互补缺陷强化群落互利关系

为避免共培养体系中某一成员脱离互作网络、独立生长甚至演化为“搭车者”，需要通过代谢依赖锁定策略增强群落成员之间的相互依赖。可采用“互补缺陷”方式建立这种依赖关系，即通过人为设计菌株的营养缺陷、代谢缺口或关键代谢产物依赖^[34]，使群落中不同成员必须依赖彼此，提供必需物质才能维持生长^[35]。这种策略能够有效减少竞争型关系，增强互利协同，提高群落组成的稳定性。特别是在长期培养或连续发酵过程中，代谢依赖锁定有助于抑制逃逸突变体和低贡献菌株的积累，从而维持群落功能的一致性^[34,36]。如Mee等^[34]对14株氨基酸缺陷大肠埃希氏菌构成的多元合成菌群开展连续50 d (约400代)传代培养发现，菌群自发收敛为甲硫氨酸、苏氨酸、异亮氨酸、赖氨酸缺陷株组成的稳定核心群落，仅在传代至400代的后期才零星产生逃逸突变个体，证明互补缺陷能长效锁定互利关系、抑制作弊株产生。

2.4 生长-产物耦联：提升异养模块的功能稳定性

在异养菌一侧应建立“生长-产物耦联”机制，即将目标产物合成与菌株生长优势绑定，使异养菌只有维持目标代谢功能时才能获得较强的生长能力^[37]。该策略可减少生产过程中因代谢负担导致的产物合成衰减，避免出现仅追求快速增殖而丧失生产能力的非生产型细胞。如在亮氨酸营养缺陷型解脂耶氏酵母(Yarrowia lipolytica)中将产物合成途径与必需基因耦联形成代谢成瘾，可使高产表型经324代留存90.9%产量，对照组300代后产量仅剩5.5%^[36]；在酿酒酵母中构建甘草次酸依赖的代谢成瘾生长回路，在连续传代中有效避免异源合成基因丢失与产量下滑；经6 d定向进化后，菌株甘草次酸产量提升46.8%，总三萜产物提升59.1%^[37]。在碳转化人工群落中，异养菌通常承担目标化合物合成任务，因此其代谢稳定性直接影响整个体系的产率与持续运行能力。通过生长-产物耦联设计，可将碳源利用、细胞增殖和目标产物形成整合为统一选择压力下的过程，从而提高产物合成效率和长期稳定性^[38]。

2.5 空间组织设计：优化群落成员的物质交换效率

鉴于自养菌与异养菌之间的协作高度依赖胞外碳源、生长因子及环境信号分子的传递，其空间分布格局与局部微环境直接制约物质扩散通量及种间互作强度。通过固定化培养、膜分隔、微载体组装及生物膜构建等策略可实现不同菌株的有序排列与空间协同^[39-40]。相关研究利用浸没式中空纤维膜生物反应器构建空间分区共培养体系，将产酸菌酪丁酸梭菌(Clostridium tyrobutyricum)与己酸合成菌产己酸巨球形菌(Megasphaera hexanoica)物理隔离：膜组件截留菌体，仅允许糖类、短链脂肪酸等小分子代谢物自由跨膜传递，既彻底消除菌株间生长竞争，又避免己酸对产酸菌的毒性作用，同时维持菌群间物质交换与代谢耦合。实验采用培养基分段转运模式运行，产酸侧发酵44 h可积累丁酸15.83 g/L，最终体系己酸产量达10.08 g/L，生产强度高达0.69 g/(L⋅h)，显著优于传统混合培养以及培养基循环模式^[41]。该工程手段具有双重优势：一方面，通过缩短关键代谢物的传递路径有效减少扩散损失，显著提升传质效率；另一方面，通过空间限域作用缓解生长速率差异引发的种间竞争，防止优势物种过度增殖导致的群落结构失衡。因此，空间架构的理性设计是实现合成群落高效物质交换与长期稳健共存的关键工程保障。

2.6 过程参数控制：维持群落运行环境的动态稳定

由于自养菌与异养菌的生理特征及最适生长环境存在显著差异，且代谢活动会动态改变局部微环境，维持群落系统的稳定状态是过程控制的核心挑战。诸多关键参数的波动通常会产生级联效应，例如，pH变化通过调节代谢产物的解离状态影响其生物利用度^[42]；温度波动通过改变酶促动力学特性进而重塑群落代谢谱；底物供应策略则直接决定固碳模块与下游代谢模块间的通量分配^[43]。自产乙醇梭菌(Clostridium autoethanogenum)合成气发酵研究表明，菌体浓度升高会造成胞外乙酸累积，引发质子动力势解偶联、ATP维持消耗上升，进而驱动碳流向乙醇等产物重分配，CO、CO₂的消耗与生成速率也随之大幅改变；胞内乙酰辅酶A还会逐步耗竭，最终造成代谢紊乱^[44]。这一现象直观体现了环境与代谢参数波动会引发级联效应，也说明对底物、产物、菌体密度等关键参数实施动态调控，维持微环境稳定，是保障菌群持续、稳定运行的关键。因此，构建集成群落结构感知、代谢状态监测及多参数精细协同的生物过程调控体系至关重要，这不仅能有效提升碳转化过程的连续性、鲁棒性与工艺可重复性，更是推动合成微生物群落从实验室验证走向大规模工业化应用的重要保障。

总之，合成微生物群落碳循环体系设计核心可概括为：以自养菌固定CO₂并输出有机碳源为起点，以异养菌利用该碳源进行生长和产物合成为主要功能，同时通过生长因子与环境调节形成反向支持，再结合代谢依赖锁定、生长-产物耦联、空间组织设计和过程参数控制等工程策略，构建稳定、高效、可持续运行的人工合成微生物群落碳循环体系。

3 典型案例分析

收起

在合成微生物群落的碳循环系统中，CO₂通过不同固碳模块先转化为可溶性有机碳，中间代谢物再由异养模块转向多种高值产物，实现碳固定与产品合成的耦联。图2展示了通过模块化设计构建人工碳循环体系的总体架构。体系被划分为3个功能独立的模块：左侧为固碳模块，利用光合微生物(如蓝藻)或化能自养微生物[如产乙酸菌、杀虫贪铜菌(Cupriavidus necator]依托光能、H₂或CO作为能量驱动力，将CO₂转化为生物质；中间为可溶性碳前体池，固碳菌将固定的碳以蔗糖、乙酸、乙醇等小分子形式分泌至胞外环境，作为跨物种传递的碳载体；右侧为异养产物合成模块，由代谢工程改造的异养菌株[如大肠埃希氏菌、恶臭假单胞菌(Pseudomonas putida)、克氏梭菌(Clostridium kluyveri)等]摄取中间碳前体，并将其定向转化为生物燃料、平台化学品或生物材料，最终实现“碳捕获-碳传输-碳利用”的完整人工循环闭环。表2整理了基于合成微生物群落的碳转化体系代表性研究案例，以下将进行详细介绍。

3.1 光驱动合成群落体系

3.1.1 蓝藻-异养菌共培养体系

以工程化蓝藻细长聚球藻(Synechococcus elongatus) cscB为核心固碳菌，通过外源表达蔗糖通道蛋白，使其在光照条件下将固定的碳转化为蔗糖并分泌到培养基中；异养菌(如E. coli、P. putida)利用蔗糖作为碳源，通过不同的代谢途径合成目标产物^[45]。例如，通过S. elongatuscscB与工程化E. coli共培养实现了蔗糖向3-羟基丙酸(3-hydroxypropionic acid, 3-HP)的转化^[46]，相较于蓝细菌纯培养，双菌共培养通过解除产物抑制、清除氧化胁迫、上调固碳基因显著提升CO₂固定效率与运行稳定性；共培养体系以CO₂为唯一初始碳源，一步合成3-HP，最终产量达68.29 mg/L，与外源补加蔗糖的大肠埃希氏菌纯培养体系产能相当^[46]。双菌合成群落既保证了目标产物得率，又简化工艺流程、降低原料与分离成本，是CO₂生物转化平台化合物的高效方案。在共培养体系中还观察到蓝藻生长速率提高和系统稳定性增强。这一体系的关键在于蔗糖分泌效率的提高及生态互惠关系的建立，当前短板为产物绝对浓度偏低，后续可通过强化蔗糖分泌、优化工程菌代谢通路进一步提升产能。

3.1.2 多产物输出的群落设计

在另一些研究中，通过引入多个异养菌株并行合成不同的目标化合物，实现了光驱动下多产物并行输出。例如在蓝藻与2株工程化E. coli的共培养体系中分别合成乙烯和异戊二烯等挥发性化学品，提高了群落的功能多样性和碳利用效率^[47]。

3.2 氢能驱动合成群落体系

3.2.1 乙酸菌+异养菌模式

该模式的气体发酵路径主要依赖厌氧自养微生物[如永达尔梭菌(Clostridium ljungdahlii)、食一氧化碳梭菌(Clostridium carboxidivorans)等]通过WL途径将CO/CO₂/H₂合成气转化为乙酸、乙醇等中间产物^[51]。在共培养体系中，异养型工程丙酮丁醇梭菌(Clostridium acetobutylicum)与自养菌Clostridium ljungdahlii利用代谢互补特性实现碳资源高效闭环，异养丙酮丁醇梭菌分解葡萄糖等有机质合成丙酮、丁醇，但糖代谢会大量释放CO₂与H₂并流失约三分之一碳，且自身无法利用无机一碳气体、不能天然合成异丙醇；C. ljungdahlii依托Wood-Ljungdahl 自养途径消耗前者副产的CO₂、H₂固碳生成乙酸，既可消除氢气对丙酮丁醇梭菌氢化酶的反馈抑制、持续供给乙酸供丙酮丁醇梭菌重吸收回收碳，还能通过脱氢酶将丙酮转化为高附加值异

丙醇^[16]。自产乙醇梭菌与链延伸菌[如克氏梭菌(Clostridium kluyveri)]联合，可将短链产物延伸为更高碳数的醇类或酸类^[48]。纯培养条件下，C. autoethanogenum可利用CO生成乙酸、乙醇，但无法合成中链产物；C. kluyveri受CO强抑制，完全不能利用气态碳源^[48]。双菌共培养体系依托菌群解毒与底物互补，彻底解除CO毒性，实现气态碳源连续固定，碳转化深度显著提升；产物层面，共培养体系可稳定合成丁酸、己酸、丁醇、己醇，体积生产速率分别达到(8.5±1.1)、(2.5±0.63)、(3.5±0.69)、(2.0±0.46) mmol/(L⋅d)，而2类中链脂肪酸与高级醇在单菌培养中均无法生成^[48]。该共培养模式打通了“CO利用-碳链延长”的完整代谢通路，不仅提升了气态碳源的固定效率与碳截留率，还实现了产物提质;该体系的优势在于直接利用廉价合成气作为碳源，并通过模块化分工提高碳链延伸效率，但需要优化pH和营养条件以维持群落稳定性并提升目标产物收率^[48]。

此外，产乙酸菌还可与好氧菌通过物理隔离进行生产耦联，如在厌氧产乙酸菌与好氧产碱杆菌构建的两级循环耦合体系中，相较于单菌独立运行模式，组合菌群在碳固定与产物合成方面优势突出^[49]。单株产乙酸菌纯培养时乙酸积累引发产物抑制，碳源利用效率快速下降；产碱杆菌无法直接固定CO₂，仅能依赖外源乙酸异养生长。双菌联动后，乙酸作为中间产物动态周转，消除毒性抑制，体系CO₂利用率稳态下接近100%；最终单细胞蛋白最大细胞干重达到17.4 g/L，菌体蛋白含量74%，平均生产强度1.5 g/(L⋅d)，产物得率与连续性大幅优于单菌工艺^[49]。两菌代谢形成pH自平衡与营养盐循环，通过培养基循环回用显著降低废水排放、缓解产物抑制并提升碳转化效率；但需进一步优化两阶段菌群的pH适配性、电子传递效率及营养供给，以强化系统稳定性与蛋白合成得率。

3.2.2 氢氧化菌+异养菌模式

Cupriavidus necator能够利用H₂作为能源、CO₂作为碳源进行自养生长，并具备强大的异养代谢能力。Nangle等^[50]通过代谢工程改造C. necator实现气源定向合成蔗糖；蔗糖作为典型高能量密度碳源，生物可利用能量为17 kJ/g，相较于糖醇、短链有机酸等发酵碳源具备显著的能量优势；改造菌株在表达蔗糖合成通路与转运蛋白后，胞外蔗糖产量提升至180 mg/L；基于该高能量中间产物，研究组合具有高效蔗糖利用能力的工程大肠埃希氏菌与酿酒酵母构建跨界共培养体系，利用蔗糖充足的代谢通量，实现多种高附加值产物的串联合成，构建了资源化利用的新型菌群发酵路线。尽管以C. necator为核心构建稳定双菌群落的案例仍在发展中，但其高密度培养特性与成熟的工程化工具使其成为CO₂基生物制造的理想底盘之一，是固碳模块与异养产物合成模块耦联的潜力菌株。

3.3 化学能驱动合成群落体系

自然界中大量化能自养微生物能够氧化Fe²⁺、硫化物、单质硫、硫代硫酸盐或亚硫酸盐^[52-53]，并将释放的电子用于呼吸链能量转化和CO₂固定^[54]。如亚铁氧化酸硫杆状菌(Acidithiobacillus ferrooxidans)可通过氧化、还原硫化物获取能量，依靠多套cbb操纵子协同调控CBB循环，具备稳定的天然固碳能力，其碳固定相关基因、转录调控网络已得到完整验证^[55]。将其与异养嗜酸嗜酸菌(Acidiphilium acidophilum)混合培养后，菌群展现出显著的协同增益效果；实验数据表明，共培养体系中目的菌株对数生长期延长2 d，菌体浓度达到纯培养的5倍；铁氧化与能量代谢效率全面提升，同时碳固定关键基因cbbLS-2与调控基因cbbR表达上调，从表型与转录层面证实合成群落对固碳能力的强化作用^[56]。2类菌株通过铁氧化-还原循环、有机物交叉利用形成互利共生体系，既延续了化能体系原料廉价、安全性高的优势，又解决了单一菌株生长受限的问题。嗜酸化能自养菌存在生长速率慢、适宜pH过低的问题，无法直接与常规酵母类蛋白菌株协同培养，需对功能菌株进行耐酸优化。相较于传统依赖H₂、光能的固碳体系，该类以Fe²⁺、还原态硫化物为电子供体的化能合成群落，原料成本更低、储运安全性更高，规避了氢气爆炸、光衰减等工程瓶颈。在此基础上，结合固定化生物膜、膜分隔等反应器技术，可进一步打造抗污染、可连续运行、易规模化的工程化生态系统，是CO₂资源化转化极具潜力的技术路线^[57-59]。

4 关键技术挑战与未来发展方向

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尽管基于合成微生物群落的CO₂生物转化体系发展迅速，但面向大规模工业化应用仍面临五大核心技术挑战，未来可通过计算设计、动态调控、多能耦合与生态工程化实现系统性突破。

(1) 固碳通量不足仍是核心瓶颈，光合、气体发酵与氢氧化自养体系的碳固定速率难以满足工业底物供给需求，需在酶效率、代谢调控、能量供给与反应器传质等方面协同升级^[60-61]。未来可依托基因组尺度代谢模型与机器学习开展计算辅助群落设计，提前预测菌株互作、碳流分配与适配培养条件，标准化蓝藻、乙酸菌、C. necator、E. coli、恶臭假单胞菌及链延伸梭菌等底盘模型库，精准提升固碳与转化通量^[62]。

(2) 碳中间体分泌不足与传递效率低，固碳菌的碳分配天然倾向自身生长，过度诱导分泌易损伤菌体活性。未来可构建动态调控型合成群落，利用光响应、氧响应、pH感应、代谢物传感器与群体感应系统，在生长阶段与生产阶段之间自动切换，在细胞增殖与碳源外排之间实现稳态平衡^[63]。

(3) 群落组成难以长期稳定，生长速率差异、代谢负担不均与突变筛选压力易造成群落漂移。未来需引入生态机制维持稳态，结合负频率依赖选择、交叉营养互补、空间分隔与生态位分化，通过模块化分工与代谢互馈设计提升群落长期鲁棒性^[64]。

(4) 工业反应器放大难度高，光合体系存在光衰减与杂菌污染问题，气体发酵受气液传质效率限制，氢氧化体系存在H₂/O₂混合爆炸的安全风险。未来应从菌株设计阶段即考虑安全便捷的还原力获取方式，除光能、H₂和CO等传统能量和电子供体外^[65]，铁离子与硫离子这类天然无机还原物质在地球化学循环中储量丰富，有望成为新型二氧化碳生物固定体系的核心还原力来源。

(5) 工程微生物的分级安全管控挑战。目前基因工程菌在密闭工业反应器中的应用技术成熟，多数产品已通过安全审批；但该类菌株若脱离封闭发酵体系，进入自然或半开放环境，将面临菌体扩散、外源基因漂移等生态隐患。针对这一问题，可采用营养缺陷、温度敏感元件、必需氨基酸依赖、CRISPR自毁等多种生物安全防控策略，构建可自我约束的工程生态系统，提升菌株环境适配性与应用安全性^[66-67]。

未来，基于合成微生物群落的人工碳循环体系将摆脱经验式的菌株筛选模式，迈向以“计算辅助设计-动态调控-多能耦合-生态闭环”为特征的一体化范式。通过精准调控电能、光能与化学能等多元还原力供给，辅以在线传感与智能协同控制，该体系可实现高效、稳健且具备工业经济价值的负碳生物制造。这一演进标志着CO₂生物利用从“单菌细胞工厂”向“人工生态系统工厂”的跨越。其核心本质并非简单的物种叠加，而是基于对菌群间碳流、能流、电子流与信息流的理性设计，实现复杂碳转化过程的系统级重构。该领域的核心突破需重点布局三大方向：首先，强化固碳模块的基础性能，提升CO₂固定效率、还原力供应能力及胞外中间体的输出水平；其次，构建稳健可控的群落互作网络，完善代谢依赖、生长-产物耦联、空间结构配置及动态时序调控机制；最后，加速推进反应器工程与评价方法创新，推动实验室概念验证体系走向具备经济可行性与显著碳减排效益的工业化应用平台。随着系统生物学、合成生态学、计算建模及自动化制造技术的深度融合，合成微生物群落必将成为人工碳循环与绿色生物制造领域的核心支撑技术。

基金

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天津市科技计划(24PTLYHZ00300)
天津市科技计划(24YFYSHZ00010)
天津市科技重大专项与工程项目(25ZXWCSY00320)
天津市合成生物技术创新能力提升行动(TSBICIP-KJGG-039)

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文献

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2026年第66卷第9期

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doi: 10.13343/j.cnki.wsxb.20260431

接收时间：2026-05-20
首发时间：2026-09-09
出版时间：2026-09-04

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出版历史

收稿日期：2026-05-20
录用日期：2026-06-28

基金

the Tianjin Science and Technology Program(24PTLYHZ00300)

天津市科技计划(24PTLYHZ00300)

天津市科技计划(24YFYSHZ00010)

the Tianjin Major Science and Technology Special Project and Engineering Project(25ZXWCSY00320)

天津市科技重大专项与工程项目(25ZXWCSY00320)

the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Action(TSBICIP-KJGG-039)

天津市合成生物技术创新能力提升行动(TSBICIP-KJGG-039)

作者信息

^1.中国科学院天津工业生物技术研究所，天津市工业生物系统与过程工程重点实验室，天津

^2.天津科技大学生物工程学院，天津

^3.合成生物国家技术创新中心，天津

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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Pathway	Representative microorganisms	Core enzymes and key characteristics	Advantages	Bottlenecks	Roles in synthetic consortia
Calvin-Benson-Bassham (CBB) cycle	Cyanobacteria, plants, some chemolithoautotrophs	RuBisCO; 3-phosphoglycerate as the primary product	Most thoroughly characterized; natively coupled with photosynthesis; compatible with light-driven systems	Low catalytic efficiency of RuBisCO; photorespiration carbon loss; light transfer limitations	Carbon-fixing module for saccharides/organic acids^[6,13]
Wood-Ljungdahl (WL) pathway	Acetogens, Clostridia, methanogenic archaea	Acetyl-CoA synthase; CO₂ converted directly to acetyl-CoA	Highest energy efficiency; compatible with syngas (CO/CO₂/H₂)	Strict anaerobic requirement; poor gas-liquid mass transfer; pH sensitivity; slow growth	Gas carbon-fixing module, acetate/ethanol supplying module^[14-15]
rTCA cycle and other native or synthetic carbon fixation pathways	Anaerobic/microaerophilic bacteria, archaea, engineered strains	ATP citrate lyase; 2-oxoglutarate synthase	High energy efficiency; short metabolic routes; diverse target products	Oxygen sensitivity; low heterologous expression efficiency of key enzymes; difficult engineering manipulation	High-specificity carbon-fixing module; chassis for synthetic pathways^[16-18]
Hydrogen-oxidizing autotrophic carbon fixation system (with CBB as carbon fixation pathway)	Cupriavidus necator and related strains	Hydrogenase; H₂ serves as electron donor	Electro-hydrogen-biological coupling; no light limitation; fast growth; capable of PHA biosynthesis	Safety hazards of H₂/O₂ mixture; strict gas proportion control; weak product secretion capacity	Electrogenic carbon-fixing module; carbon intermediate supplying module^[19-20]

Pathway

Representative microorganisms

Core enzymes and key characteristics

Advantages

Bottlenecks

Roles in synthetic consortia

Calvin-Benson-Bassham (CBB) cycle

Cyanobacteria, plants, some chemolithoautotrophs

RuBisCO; 3-phosphoglycerate as the primary product

Most thoroughly characterized; natively coupled with photosynthesis; compatible with light-driven systems

Low catalytic efficiency of RuBisCO; photorespiration carbon loss; light transfer limitations

Carbon-fixing module for saccharides/organic acids^[6,13]

Wood-Ljungdahl (WL) pathway

Acetogens, Clostridia, methanogenic archaea

Acetyl-CoA synthase; CO₂ converted directly to acetyl-CoA

Highest energy efficiency; compatible with syngas (CO/CO₂/H₂)

Strict anaerobic requirement; poor gas-liquid mass transfer; pH sensitivity; slow growth

Gas carbon-fixing module, acetate/ethanol supplying module^[14-15]

rTCA cycle and other native or synthetic carbon fixation pathways

Anaerobic/microaerophilic bacteria, archaea, engineered strains

ATP citrate lyase; 2-oxoglutarate synthase

High energy efficiency; short metabolic routes; diverse target products

Oxygen sensitivity; low heterologous expression efficiency of key enzymes; difficult engineering manipulation

High-specificity carbon-fixing module; chassis for synthetic pathways^[16-18]

Hydrogen-oxidizing autotrophic carbon fixation system (with CBB as carbon fixation pathway)

Cupriavidus necator and related strains

Hydrogenase; H₂ serves as electron donor

Electro-hydrogen-biological coupling; no light limitation; fast growth; capable of PHA biosynthesis

Safety hazards of H₂/O₂ mixture; strict gas proportion control; weak product secretion capacity

Electrogenic carbon-fixing module; carbon intermediate supplying module^[19-20]

Carbon fixation module	Downstream module	Forms of carbon sources	Target products	Cooperation mechanism	Main advantages	Key challenges
SynechococcuscscB	Pseudomonas putidacscAB	Sucrose	Polyhydroxyalkanoates (PHA)	Commensalism: cyanobacteria conduct photosynthetic carbon fixation and secrete sucrose, while Pseudomonas sp. utilizes sucrose to synthesize polyhydroxyalkanoate (PHA)	Platformized and scalable	Carbon flux competition^[45]
Synechococcus elongatus UTEX 2973	E. coli BL21 (DE3)	Sucrose	3-hydroxypropionic acid (3-HP)	Mutualistic symbiosis: cyanobacteria fix carbon via photosynthesis and secrete sucrose, while Escherichia coli utilizes sucrose to synthesize 3-HP and eliminate reactive oxygen species (ROS)	The growth of cyanobacteria was markedly improved	Dynamic control of microbial community ratios^[46]
Synechococcus elongatus PCC79429 (cscB)	E. coli BL21 (efe, ispS)	Sucrose	Ethylene, isoprene	Commensalism (cyanobacteria secrete sugars and oxygen, while Escherichia coli utilizes sucrose to synthesize ethylene and isoprene)	Light-driven, short integrated metabolic pathway	Limited sucrose flux, photoinhibition^[47]
Clostridium acetobutylicum	Clostridium kluyveri	CO/CO₂→acetic acid	Butanol, hexanol	Mutualistic symbiosis: Clostridium ljungdahlii consumes and detoxifies CO while supplying acetate and ethanol; Clostridium kluyveri utilizes these substrates to elongate carbon chains and synthesize medium-chain fatty acids and higher alcohols	Carbon chain elongation with high carbon yields	pH control^[48]
Engineered Clostridium acetobutylicum	Clostridium ljungdahlii	Sugars+CO₂	Isopropanol, butanol	Mutualistic symbiosis: Clostridium acetobutylicum produces CO₂, H₂, and acetone; Clostridium ljungdahlii fixes carbon, converts acetone to isopropanol, and generates acetate to feed back to the primary strain	Enhance carbon utilization efficiency	Maintain community stability^[16]
Acetobacterium	Alcaligenes	CO₂+electricity (electrolytic H₂ generation)	Single cell protein (SCP)	Mutualistic symbiosis: Acetobacter produces acetate to feed Alcaligenes, while Alcaligenes consumes acetate to relieve metabolic inhibition and balance the pH of the system	Alleviated product inhibition, low wastewater generation, nearly 100% gas utilization efficiency, high protein content	Low electron-to-protein conversion efficiency and high risk of membrane fouling during long-term operation^[49]
Cupriavidus necator	Escherichia coli, Saccharomyces cerevisiae	CO₂+H₂	PHA/other chemicals	Cupriavidus performs chemolithoautotrophic carbon fixation and secretes sucrose to support heterotrophs; heterotrophs consume sucrose to relieve product inhibition and drive upstream biosynthesis	High cell density, industrial potential	Cases of co-cultivation remain scarce^[50]

Carbon fixation module

Downstream module

Forms of carbon sources

Target products

Cooperation mechanism

Main advantages

Key challenges

SynechococcuscscB

Pseudomonas putidacscAB

Sucrose

Polyhydroxyalkanoates (PHA)

Commensalism: cyanobacteria conduct photosynthetic carbon fixation and secrete sucrose, while Pseudomonas sp. utilizes sucrose to synthesize polyhydroxyalkanoate (PHA)

Platformized and scalable

Carbon flux competition^[45]

Synechococcus elongatus UTEX 2973

E. coli BL21 (DE3)

Sucrose

3-hydroxypropionic acid (3-HP)

Mutualistic symbiosis: cyanobacteria fix carbon via photosynthesis and secrete sucrose, while Escherichia coli utilizes sucrose to synthesize 3-HP and eliminate reactive oxygen species (ROS)

The growth of cyanobacteria was markedly improved

Dynamic control of microbial community ratios^[46]

Synechococcus elongatus PCC79429

(cscB)

E. coli BL21 (efe, ispS)

Sucrose

Ethylene, isoprene

Commensalism (cyanobacteria secrete sugars and oxygen, while Escherichia coli utilizes sucrose to synthesize ethylene and isoprene)

Light-driven, short integrated metabolic pathway

Limited sucrose flux, photoinhibition^[47]

Clostridium acetobutylicum

Clostridium kluyveri

CO/CO₂→acetic acid

Butanol, hexanol

Mutualistic symbiosis: Clostridium ljungdahlii consumes and detoxifies CO while supplying acetate and ethanol; Clostridium kluyveri utilizes these substrates to elongate carbon chains and synthesize medium-chain fatty acids and higher alcohols

Carbon chain elongation with high carbon yields

pH control^[48]

Engineered Clostridium acetobutylicum

Clostridium ljungdahlii

Sugars+CO₂

Isopropanol, butanol

Mutualistic symbiosis: Clostridium acetobutylicum produces CO₂, H₂, and acetone; Clostridium ljungdahlii fixes carbon, converts acetone to isopropanol, and generates acetate to feed back to the primary strain

Enhance carbon utilization efficiency

Maintain community stability^[16]

Acetobacterium

Alcaligenes

CO₂+electricity (electrolytic H₂ generation)

Single cell protein (SCP)

Mutualistic symbiosis: Acetobacter produces acetate to feed Alcaligenes, while Alcaligenes consumes acetate to relieve metabolic inhibition and balance the pH of the system

Alleviated product inhibition, low wastewater generation, nearly 100% gas utilization efficiency, high protein content

Low electron-to-protein conversion efficiency and high risk of membrane fouling during long-term operation^[49]

Cupriavidus necator

Escherichia coli, Saccharomyces cerevisiae

CO₂+H₂

PHA/other chemicals

Cupriavidus performs chemolithoautotrophic carbon fixation and secretes sucrose to support heterotrophs; heterotrophs consume sucrose to relieve product inhibition and drive upstream biosynthesis

High cell density, industrial potential

Cases of co-cultivation remain scarce^[50]