非模式微生物在CO<sub>2</sub>生物转化中的底盘开发潜力与工程化策略

廖勤; 梁光杰; 徐淑芬; 高聪; 刘佳; 李晓敏; 宋伟; 刘立明

doi:10.12211/2096-8280.2026-103

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非模式微生物在CO₂生物转化中的底盘开发潜力与工程化策略

特约评述 | 更新时间：2026-10-30

- 非模式微生物在CO₂生物转化中的底盘开发潜力与工程化策略
- Chassis development potential and engineering strategies for non-model microorganisms in CO₂-based biotransformation
- 合成生物学 2026年页码：1-18
- 作者机构：
  
  1.江南大学生物工程学院，工业生物技术教育部重点实验室，江苏无锡 214122
  2.江南大学生命科学与健康学院，工业生物技术教育部重点实验室，江苏无锡 214122
- 作者简介：
  
  廖勤（2002—），女，博士研究生。研究方向为微生物细胞工厂。
  刘立明（1976—），男，教授、博士生导师，教育部高层次人才。研究方向为合成生物学技术和微生物细胞工厂。
- 基金信息：
  
  国家自然科学基金区域创新发展联合基金(U25A20618);榆林中科洁净能源创新研究院能源革命科技专项(E411040705);国家资助博士后研究人员计划（Grade C）;中国博士后科学基金(GZC20251635);江苏省卓越博士后计划(2025ZB841);中国博士后科学基金面上资助(2025M782519)
- DOI：10.12211/2096-8280.2026-103
  中图分类号： Q815
- 收稿：2026-09-09，
  
  修回：2026-10-29，
  
  网络首发：2026-10-30，
- 稿件说明：
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廖勤，梁光杰，徐淑芬，高聪，刘佳，李晓敏，宋伟，刘立明. 非模式微生物在CO₂生物转化中的底盘开发潜力与工程化策略［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-103

LIAO Qin， LIANG Guangjie， XU Shufen， GAO Cong， LIU Jia， LI Xiaomin， SONG Wei， LIU Liming. Chassis development potential and engineering strategies for non-model microorganisms in CO₂-based biotransformation［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-103
廖勤，梁光杰，徐淑芬，高聪，刘佳，李晓敏，宋伟，刘立明. 非模式微生物在CO₂生物转化中的底盘开发潜力与工程化策略［J］. 合成生物学， 2026， 7. DOI： 10.12211/2096-8280.2026-103 DOI：

LIAO Qin， LIANG Guangjie， XU Shufen， GAO Cong， LIU Jia， LI Xiaomin， SONG Wei， LIU Liming. Chassis development potential and engineering strategies for non-model microorganisms in CO₂-based biotransformation［J］. Synthetic Biology Journal， 2026， 7. DOI： 10.12211/2096-8280.2026-103 DOI：

摘要

既是驱动全球气候变化的主要温室气体之一，也是自然界丰富的一碳资源。发展高效的CO

生物捕集与转化技术，并将其转化为有机酸、酯、醇和醚等高值化学品，有助于推进CO

资源化利用、降低化工生产对化石碳源的依赖，对实现我国“碳达峰”和“碳中和”目标具有重要意义。与模式微生物相比，非模式微生物具有多样化的固碳途径、能量代谢模式和环境适应能力，是构建新一代CO

生物转化底盘的重要生物资源。本文从以下3个方面系统综述非模式微生物用于CO

生物转化的研究进展：（1）具有CO

生物转化潜力的非模式微生物类型及其代谢特征；（2）非模式微生物固碳元件的挖掘、改造与应用；（3）制约非模式微生物底盘性能的关键因素及相应的工程化策略。在此基础上，分析非模式微生物在固碳元件资源开发、底盘可预测设计以及工业化性能保持等方面的不足，并提出通过蛋白质语言模型与高通量功能验证拓展复杂固碳元件资源、整合多组学数据与代谢模型提高底盘改造可预测性，以及加强工业相关条件下菌株性能验证与过程放大评价等未来研究方向，以期促进非模式微生物由天然固碳资源向可设计、可调控、高效稳定的工程化CO

生物转化底盘转变。

Abstract

Carbon dioxide (CO

) is a major greenhouse gas driving global climate change

while also serving as an abundant and renewable one-carbon feedstock. Developing efficient biological technologies for CO

capture and conversion into value-added products

such as organic acids

esters

alcohols

and ethers

provides a promising route for carbon valorization and can reduce the dependence of chemical manufacturing on fossil-derived carbon resources. These efforts are also of strategic importance for advancing sustainable biotransformation and supporting carbon-peaking and carbon-neutrality goals. Compared with conventional model microorganisms

non-model microorganisms often possess diverse native carbon fixation pathw

ays

energy conservation mechanisms

redox strategies

and environmental adaptation traits

making them valuable biological resources for developing next-generation microbial chassis for CO

-based biotransformation. This review summarizes recent advances in the development and engineering of non-model microorganisms for CO

biotransformation from three perspectives. First

representative groups of non-model microorganisms with potential for CO

conversion are discussed

with emphasis on their carbon fixation pathways

energy and electron utilization strategies

physiological characteristics

and biotransformation applications. Second

we review the discovery

engineering

and application of carbon fixation-related components derived from non-model microorganisms

including key carboxylases

-reducing enzymes

and auxiliary functional modules

and highlight their potential as a resource base for constructing natural and synthetic carbon assimilation systems. Third

we analyze major constraints that limit the development of non-model microorganisms into efficient production chassis

including incomplete genetic and functional characterization

limited genetic tractability

poorly predictable metabolic networks

imbalances in energy and reducing-equivalent supply

and insufficient robustness under industrially relevant conditions. Corresponding engineering strategies

including functional genomics

genome editing

metabolic network reconstruction

energy metabolism optimization

adaptive laboratory evolution

and process engineering

are also summarized. Finally

we identify key challenges in expanding the repertoire of exploitable carbon fixation components

improving the predictability and controllability of chassis engineering

and maintaining stable production performance under industrial conditions. Future efforts should emphasize the integration of component discovery

systems-level modeling

chassis engineering

and process optimization to transform non-model mic

roorganisms into efficient

robust

and controllable microbial platforms for CO

biotransformation.

关键词

Keywords

references

BACHLEITNER S , ATA O , MATTANOVICH D . The potential of CO 2 -based production cycles in biotechnology to fight the climate crisis [J ] . Nature Communications , 2023 , 14 ( 1 ): 6978 .

KURT E , QIN J , WILLIAMS A , et al . Perspectives for Using CO 2 as a Feedstock for Biomanufacturing of Fuels and Chemicals [J ] . Bioengineering , 2023 , 10 ( 12 ): 1357 .

MEUNIER N , CHAUVY R , MOUHOUBI S , et al . Alternative production of methanol from industrial CO 2 [J ] . Renewable Energy , 2020 , 146 ( 2 ): 1192 - 1203 .

SONG C , LIU Q , QI Y , et al . Absorption-microalgae hybrid CO 2 capture and biotransformation strategy—A review [J ] . International Journal of Greenhouse Gas Control , 2019 , 88 ( 1 ): 109 - 117 .

ZHAO C , ZHU P , CHAI T , et al . Biological conversion of CO 2 for bioproduction: beyond natural limitations [J ] . Chemical Society Reviews , 2026 , 55 ( 14 ): 7487 - 7548 .

ANTONOVSKY N , GLEIZER S , NOOR E , et al . Sugar Synthesis from CO 2 in Escherichia coli [J ] . Cell , 2016 , 166 ( 1 ): 115 - 125 .

FENG J , MA D , GAO S , et al . Recent Advances in Engineering Heterotrophic Microorganisms for Reinforcing CO 2 Fixation Based on Calvin–Benson–Bassham Cycle [J ] . ACS Sustainable Chemistry & Engineering , 2023 , 11 ( 26 ): 9509 - 9522 .

KOPKE M , HELD C , HUJER S , et al . Clostridium ljungdahlii represents a microbial production platform based on syngas [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2010 , 107 ( 29 ): 13087 - 13092 .

RUAN S , JIANG Y , WANG A , et al . Carbon sequestration pathways in microorganisms: Advances, strategies, and applications [J ] . Engineering Microbiology , 2025 , 5 ( 2 ): 100196 .

BIERBAUMER S , NATTERMANN M , SCHULZ L , et al . Enzymatic Conversion of CO 2 : From Natural to Artificial Utilization [J ] . Chemical Reviews , 2023 , 123 ( 9 ): 5702 - 5754 .

SCHUCHMANN K , MÜLLER V . Direct and Reversible Hydrogenation of CO 2 to Formate by a Bacterial Carbon Dioxide Reductase [J ] . Science , 2013 , 342 ( 6164 ): 1382 - 1385 .

NISHIHARA A , KATO S , OHKUMA M . Exploring the Diversity and Metabolic Potential of CO 2 fixation Mediated by RubisCO in Prokaryotes in the Japan Collection of Microorganisms [J ] . Microbes and Environments , 2026 , 41 ( 1 ): ME25035 .

SCHWARZ F M , SCHUCHMANN K , MULLER V . Hydrogenation of CO 2 at ambient pressure catalyzed by a highly active thermostable biocatalyst [J ] . Biotechnology for Biofuels , 2018 , 11 ( 1 ): 237 .

SCHWANDER T , SCHADA VON BORZYSKOWSKI L , BURGENER S , et al . A synthetic pathway for the fixation of carbon dioxide in vitro [J ] . Science , 2016 , 354 ( 6314 ): 900 - 904 .

BAE J , PARK C , JUNG H , et al . Harnessing acetogenic bacteria for one-carbon valorization toward sustainable chemical production [J ] . RSC Chemical Biology , 2024 , 5 ( 9 ): 812 - 832 .

SRISAWAT P , HIGUCHI-TAKEUCHI M , NUMATA K . Microbial autotrophic biorefineries: Perspectives for biopolymer production [J ] . Polymer Journal , 2022 , 54 ( 10 ): 1139 - 1151 .

ZHANG J Z , LI Y Z , XI Z N , et al . Engineered acetogenic bacteria as microbial cell factory for diversified biochemicals [J ] . Frontiers in Bioengineering and Biotechnology , 2024 , 12 : 1395540 .

BOURGADE B , MINTON N P , ISLAM M A . Genetic and metabolic engineering challenges of C1-gas fermenting acetogenic chassis organisms [J ] . FEMS Microbiology Reviews , 2021 , 45 ( 2 ): fuab008 .

HWANG S , JOUNG C , KIM W , et al . Recent advances in non-model bacterial chassis construction [J ] . Current Opinion in Systems Biology , 2023 , 36 : 100471 .

LU L , SHEN X , SUN X , et al . CRISPR-based metabolic engineering in non-model microorganisms [J ] . Current Opinion in Biotechnology , 2022 , 75 : 102698 .

SANTOS CORREA S , SCHULTZ J , LAUERSEN K J , et al . Natural carbon fixation and advances in synthetic engineering for redesigning and creating new fixation pathways [J ] . Journal of Advanced Research , 2023 , 47 : 75 - 92 .

BAI Z , GU J , XU Y , et al . Enzymes for CO 2 fixation: Discovery, engineering, and applications [J ] . Biotechnology Advances , 2026 , 91 : 108960 .

DELLA VALLE S , TU W , HUANG W E . Construction of microbial platform chassis for CO 2 utilisation [J ] . Current Opinion in Systems Biology , 2024 , 37 : 100489 .

FUCHS G . Alternative pathways of carbon dioxide fixation: insights into the early evolution of life? [J ] . Annual Review of Microbiology , 2011 , 65 : 631 - 658 .

LEE H , BAE J , JIN S , et al . Engineering Acetogenic Bacteria for Efficient One-Carbon Utilization [J ] . Frontiers in Microbiology , 2022 , 13 : 865168 .

PRESSLEY S R , GONZALES J N , ATSUMI S . Efficient utilization of xylose requ ires CO 2 fixation in Synechococcus elongatus PCC 7942 [J ] . Metabolic Engineering , 2024 , 86 : 115 - 123 .

WANG B , ZUNIGA C , GUARNIERI M T , et al . Metabolic engineering of Synechococcus elongatus 7942 for enhanced sucrose biosynthesis [J ] . Metabolic Engineering , 2023 , 80 : 12 - 24 .

FENG L , JIA D , WANG Z , et al . FIB-SEM combined with proteomics and modification omics clarified mechanisms of lipids synthesis in organelles of Chlorella pyrenoidosa cells with high CO 2 concentration [J ] . Science of the Total Environment , 2023 , 891 : 164516 .

GUO S , LI F , WANG J , et al . Two-stage carbon sequestration by Haematococcus pluvialis : Integrated research from small-scale to pilot-scale cultivation and data quality monitoring [J ] . Bioresource Technology , 2025 , 416 : 131828 .

YE Y , LIU M , YU L , et al . Nannochloropsis as an Emerging Algal Chassis for Light-Driven Synthesis of Lipids and High-Value Products [J ] . Marine Drugs , 2024 , 22 ( 2 ): 54 .

HALLENBECK P C , LIU Y . Recent advances in hydrogen production by photosynthetic bacteria [J ] . International Journal of Hydrogen Energy , 2016 , 41 ( 7 ): 4446 - 4454 .

XU W , CHAI C , SHAO L , et al . Metabolic engineering of Rhodopseudomonas palustris for squalene production [J ] . Journal of Industrial Microbiology and Biotechnology , 2016 , 43 ( 5 ): 719 - 725 .

ZARZYCKI J , BRECHT V , MÜLLER M , et al . Identifying the missing steps of the autotrophic 3-hydroxypropionate CO 2 fixation cycle in Chloroflexus aurantiacus [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2009 , 106 ( 50 ): 21317 - 21322 .

LAUER I , PHILIPPS G , JENNEWEIN S . Metabolic engineering of Clostridium ljungdahlii for the production of hexanol and butanol from CO 2 and H 2 [J ] . Microbial Cell Factories , 2022 , 21 ( 1 ): 85 .

WAN S , LAI M , GAO X , et al . Recent progress in engineering Clostridium autoethanogenum to synthesize the biochemicals and biocommodities [J ] . Synthetic and Systems Biotechnology , 2024 , 9 ( 1 ): 19 - 25 .

WU Y , YE W , LI R , et al . Engineering Clostridium ljungdahlii for efficient 3-hydroxybutyrate production from one-carbon gases [J ] . Green Synthesis and Catalysis , 2026 , 7 ( 4 ): 488 - 492 .

DONATI S , JOHNSON C W . Optimizing Cupriavidus necator H16 as a host for aerobic C1 conversion [J ] . Current Opinion in Biotechnology , 2025 , 93 : 103306 .

SPATOLA ROSSI T , FRANCESCATO L , GUPTE A P , et al . Harnessing the potential of Cupriavidus necator for CO 2 capture from alcoholic fermentation and its bioconversion into poly(3-hydroxybutyrate) [J ] . Bioresource Technology , 2025 , 419 : 132060 .

SERNA-GARCIA R , MORLINO M S , BUCCI L , et al . Biological carbon capture from biogas streams: Insights into Cupriavidus necator autotrophic growth and transcriptional profile [J ] . Bioresource Technology , 2024 , 399 : 130556 .

CWICKLINSKI G , MIRAS R , PÉRARD J , et al . Development of a CO 2 -biometh anation reactor for producing methane from green H 2 [J ] . Sustainable Energy & Fuels , 2024 , 8 ( 5 ): 1068 - 1076 .

GHIOTTO G , DE BERNARDINI N , ORELLANA E , et al . Impact of trace metal supplementation on anaerobic biological methanation under hydrogen and carbon dioxide starvation [J ] . npj Biofilms and Microbiomes , 2025 , 11 ( 1 ): 7 .

HOLDEN J F , SISTU H . Formate and hydrogen in hydrothermal vents and their use by extremely thermophilic methanogens and heterotrophs [J ] . Frontiers in Microbiology , 2023 , 14 : 1093018 .

MUHLING L , BAUR T , MOLITOR B . Methanothermobacter thermautotrophicus and Alternative Methanogens: Archaea-Based Production [J ] . Advances in Biochemical Engineering/Biotechnology , 2025 , 192 : 27 - 58 .

GARRITANO A N , SONG W , THOMAS T . Carbon fixation pathways across the bacterial and archaeal tree of life [J ] . PNAS Nexus , 2022 , 1 ( 5 ): pgac226 .

SCOTT K M , PAYNE R R , GAHRAMANOVA A . Widespread dissolved inorganic carbon-modifying toolkits in genomes of autotrophic Bacteria and Archaea and how they are likely to bridge supply from the environment to demand by autotrophic pathways [J ] . Applied and Environmental Microbiology , 2024 , 90 ( 2 ): e01557-23 .

MANESH M J H , BING R G , WILLARD D J , et al . Complete genome sequence for the thermoacidophilic archaeon Metallosphaera sedula (DSM:5348) [J ] . Microbiology Resource Announcements , 2024 , 13 ( 3 ): e01228-23 .

SEDLMAYR V L , LUGER M , PITTENAUER E , et al . Development of a defined medium for the heterotrophic cultivation of Metallosphaera sedula [J ] . Extremophiles , 2024 , 28 ( 3 ): 36 .

BAR-EVEN A , NOOR E , LEWIS N E , et al . Design and analysis of synthetic carbon fixation pathways [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2010 , 107 ( 19 ): 8889 - 8894 .

RAGSDALE S W . The Eastern and Western branches of the Wood/Ljungdahl pathway: how the East and West were won [J ] . BioFactors , 1997 , 6 : 3 - 11 .

MARTINEZ A , BRADLEY A S , WALDBAUER J R , et al . Proteorhodopsin photosystem gene expression enables photophosphorylation in a heterologous host [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2007 , 104 ( 13 ): 5590 - 5595 .

KIM B W , CHANG H N , KIM I K , et al . Growth Kinetics of the Photosynthetic Bacterium Chlorobium thiosulfatophilum in a Fed-Batch Reactor [J ] . Biotechnology and Bioengineering , 1992 , 40 ( 5 ): 583 - 592 .

HERTER S , FARFSING J , GAD'ON N , et al . Autotrophic CO 2 fixation by Chloroflexus aurantiacus : study of glyoxylate formation and assimilation via the 3-hydroxypropionate cycle [J ] . Journal of Bacteriology , 2001 , 183 ( 14 ): 4305 - 4316 .

BERG I A , KOCKELKORN D , BUCKEL W , et al . A 3-hydroxypropionate/4-hydroxybutyrate autotrophic carbon dioxide assimilation pathway in Archaea [J ] . Science , 2007 , 318 ( 5857 ): 1782 - 1786 .

GARCIA-GONZALEZ L , DE WEVER H . Valorisation of CO 2 -rich off-gases to biopolymers through biotechnological process [J ] . FEMS Microbiology Letters , 2017 , 364 ( 20 ): fnx196 .

HUBER H , GALLENBERGER M , JAHN U , et al . A dicarboxylate/4-hydroxybutyrate autotrophic carbon assimilation cycle in the hyperthermophilic Archaeum Ignicoccus hospitalis [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2008 , 105 ( 22 ): 7851 - 7856 .

KÖPKE M , MIHALCEA C , LIEW F , et al . 2,3-Butanediol Production by Acetogenic Bacteria, an Alternative Route to Chemical Synthesis, Using Industrial Waste Gas [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 15 ): 5467 - 5475 .

LIEW F , MARTIN M E , TAPPEL R C , et al . Gas Fermentation-A Flexible Platform for Commercial Scale Production of Low-Carbon-Fuels and Chemicals from Waste and Renewable Feedstocks [J ] . Frontiers in Microbiology , 2016 , 7 : 694 .

JACK J , LO J , MANESS P-C , et al . Directing Clostridium ljungdahlii fermentation products via hydrogen to carbon monoxide ratio in syngas [J ] . Biomass and Bioenergy , 2019 , 124 : 95 - 101 .

MORLINO M S , SERNA GARCIA R , SAVIO F , et al . Cupriavidus necator as a platform for polyhydroxyalkanoate production: An overview of strains, metabolism, and modeling approaches [J ] . Biotechnology Advances , 2023 , 69 : 108264 .

POHLMANN A , FRICKE W F , REINECKE F , et al . Genome sequence of the bioplastic-producing "Knallgas" bacterium Ralstonia eutropha H16 [J ] . Nature Biotechnology , 2006 , 24 ( 10 ): 1257 - 1262 .

SANTIN A , SPATOLA ROSSI T , MORLINO M S , et al . Autotrophic poly-3-hydroxybutyrate accumulation in Cupriavidus necator for sustainable bioplastic production triggered by nutrient starvation [J ] . Bioresource Technology , 2024 , 406 : 131068 .

ENZMANN F , MAYER F , ROTHER M , et al . Methanogens: biochemical background and biotechnological applications [J ] . AMB Express , 2018 , 8 : 1 .

THAUER R K , KASTER A-K , SEEDORF H , et al . Methanogenic archaea: ecologically relevant differences in energy conservation [J ] . Nature Reviews Microbiology , 2008 , 6 ( 8 ): 579 - 591 .

DE POORTER L M , GEERTS W J , KELTJENS J T . Coupling of Methanothermobacter thermautotrophicus methane formation and growth in fed-batch and continuous cultures under different H 2 gassing regimens [J ] . Applied and Environmental Microbiology , 2007 , 73 ( 3 ): 740 - 749 .

RAMOS-VERA W H , BERG I A , FUCHS G . Autotrophic carbon dioxide assimilation in Thermoproteales revisited [J ] . Journal of Bacteriology , 2009 , 191 ( 13 ): 4286 - 4297 .

LIN P C , ZHANG F , PAKRASI H B . Enhanced limonene production in a fast-growing cyanobacterium through combinatorial metabolic engineering [J ] . Metabolic Engineering Communications , 2021 , 12 : e00164 .

OLIVER N J , RABINOVITCH-DEERE C A , CARROLL A L , et al . Cyanobacterial metabolic engineering for biofuel and chemical production [J ] . Current Opinion in Chemical Biology , 2016 , 35 : 43 - 50 .

RUFFING A M . Improved Free Fatty Acid Production in Cyanobacteria with Synechococcus sp. PCC 7002 as Host [J ] . Frontiers in Bioengineering and Biotechnology , 2014 , 2 : 17 .

ATSUMI S , HIGASHIDE W , LIAO J C . Direct photosynthetic recycling of carbon dioxide to isobutyraldehyde [J ] . Nature Biotechnology , 2009 , 27 ( 12 ): 1177 - 1180 .

DEXTER J , FU P . Metabolic engineering of cyanobacteria for ethanol production [J ] . Energy & Environmental Science , 2009 , 2 ( 8 ): 857 - 864 .

AJJAWI I , VERRUTO J , AQUI M , et al . Lipid production in Nannochloropsis gaditana is doubled by decreasing expression of a single transcriptional regulator [J ] . Nature Biotechnology , 2017 , 35 ( 7 ): 647 - 652 .

GUERIN M , HUNTLEY M E , OLAIZOLA M . Haematococcus astaxanthin: applications for human health and nutrition [J ] . Trends in Biotechnology , 2003 , 21 ( 5 ): 210 - 216 .

NAVALHO S , FERRER-LEDO N , BARBOSA M J , et al . Nannochloropsis Lipids and Polyunsaturated Fatty Acids: Potential Applications and Strain Improvement [J ] . Marine Drugs , 2025 , 23 ( 3 ): 128 .

MUZZIOTTI D , ADESSI A , FARALONI C , et al . H 2 production in Rhodopseudomonas palustris as a way to cope with high light intensities [J ] . Research in Microbiology , 2016 , 167 ( 5 ): 350 - 356 .

GOMEZ A , TINZL M , STOFFEL G , et al . Infrared spectroscopy reveals metal-independent carbonic anhydrase activity in crotonyl-CoA carboxylase/reductase [J ] . Chemical Science , 2024 , 15 ( 13 ): 4960 - 4968 .

RECABARREN R , TINZL M , SAEZ D , et al . Covalent adduct formation as strategy for efficient CO 2 fixation in crotonyl-CoA carboxylases/reductases [J ] . ACS Catalysis , 2023 , 13 ( 9 ): 6230 - 6241 .

DAVIDI D , SHAMSHOUM M , GUO Z , et al . Highly active rubiscos discovered by systematic interrogation of natural sequence diversity [J ] . The EMBO Journal , 2020 , 39 ( 18 ): e104081 .

MCDONALD J L , SHAPIRO N P , MENGISTE A A , et al . In vivo directed evolution of an ultrafast Rubisco from a semianaerobic environment imparts oxygen resistance [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2025 , 122 ( 27 ): e2505083122 .

HARMER J R , HAKOPIAN S , NIKS D , et al . Redox Characterization of the Complex Molybdenum Enzyme Formate Dehydrogenase from Cupriavidus necator [J ] . Journal of the American Chemical Society , 2023 , 145 ( 47 ): 25850 - 25863 .

NIKS D , HAKOPIAN S , CANCHOLA A , et al . Mechanism of Action of Formate Dehydrogenases [J ] . Journal of the American Chemical Society , 2024 , 146 ( 42 ): 28601 - 28604 .

RUICKOLDT J , KREIBICH J , BICK T , et al . Ligand binding to a Ni-Fe cluster orchestrates conformational changes of the CO-dehydrogenase-acetyl-CoA synthase complex [J ] . Nature Catalysis , 2025 , 8 ( 7 ): 657 - 667 .

LIU W , ZHANG K , LIU J , et al . Bioelectrocatalytic carbon dioxide reduction by an engineered formate dehydrogenase from Thermoanaerobacter kivui [J ] . Nature Communications , 2024 , 15 ( 1 ): 9962 .

KUPRIYANOVA E , PRONINA N , LOS D . Carbonic anhydrase - a universal enzyme of the carbon-based life [J ] . Photosynthetica , 2017 , 55 ( 1 ): 3 - 19 .

ROURKE L M , BYRT C S , LONG B M , et al . Functional characterization of bicarbonate transporters from the cyanobacterial SbtA2 family and subsequent expression in tobacco [J ] . Journal of Experimental Botany , 2026 , 77 ( 10 ): 3053 - 3068 .

TSAI Y C , LAPINA M C , BHUSHAN S , et al . Identification and characterization of multiple rubisco activases in chemoautotrophic bacteria [J ] . Nature Communications , 2015 , 6 : 8883 .

JAIN S , DIETRICH H M , MULLER V , et al . Formate Is Required for Growth of the Thermophilic Acetogenic Bacterium Thermoanaerobacter kivui Lacking Hydrogen-Dependent Carbon Dioxide Reductase (HDCR) [J ] . Frontiers in Microbiology , 2020 , 11 : 59 .

LIU X Y , HOU W T , WANG L , et al . Structures of cyanobacterial bicarbonate transporter SbtA and its complex with PII-like SbtB [J ] . Cell Discovery , 2021 , 7 ( 1 ): 63 .

CHEN T , FANG Y , JIANG Q , et al . Incorporation of Functional Rubisco Activases into Engineered Carboxysomes to Enhance Carbon Fixation [J ] . ACS Synthetic Biology , 2022 , 11 ( 1 ): 154 - 161 .

BOHNKE S , PERNER M . Seeking active RubisCOs from the currently uncultured microbial majority colonizing deep-sea hydrothermal vent environments [J ] . The ISME Journal , 2019 , 13 ( 10 ): 2475 - 2488 .

BANDA D M , PEREIRA J H , LIU A K , et al . Novel Bacterial Clade Reveals Origin of Form I Rubisco [J ] . Nature Plants , 2020 , 6 : 1158 - 1166 .

VARALJAY V A , SATAGOPAN S , NORTH J A , et al . Functional metagenomic selection of ribulose 1, 5-bisphosphate carboxylase/oxygenase from uncultivated bacteria [J ] . Environmental Microbiology , 2016 , 18 ( 4 ): 1187 - 1199 .

BOHNKE S , PERNER M . A function-based screen for seeking RubisCO active clones from metagenomes: novel enzymes influencing RubisCO activity [J ] . The ISME Journal , 2015 , 9 ( 3 ): 735 - 745 .

DAY L A , LIPSON R S , WETMORE K M , et al . High-throughput genetics enables identification of nutrient utilization and accessory energy metabolism genes in a model methanogen [J ] . mBio , 2024 , 15 ( 9 ): e00781-24 .

DESMARAIS J J , FLAMHOLZ A I , BLIKSTAD C , et al . DABs are inorganic carbon pumps found throughout prokaryotic phyla [J ] . Nature Microbiology , 2019 , 4 ( 12 ): 2204 - 2215 .

CAI Z , LIU G , ZHANG J , et al . Development of an activity-directed selection system enabled significant improvement of the carboxylation efficiency of Rubisco [J ] . Protein & Cell , 2014 , 5 ( 7 ): 552 - 562 .

GHAEDIZADEH S , ZEINALI M , KHAJEH K , et al . Boosting the thermal stability and catalytic efficiency of Sulfurihydrogenibium yellowstonense carbonic anhydrase through proline substitutions [J ] . The FEBS Journal , 2025 , 292 ( 23 ): 6420 - 6431 .

LI S , ZHOU J , SONG X , et al . Enhancing the Catalytic Activity of Thermococcus kodakarensis RuBisCo via Computer-Aided Rational Design [J ] . Journal of Agricultural and Food Chemistry , 2026 , 74 ( 17 ): 14055 - 14063 .

ZHANG J , ZHAO L , LIU G , et al . A single amino acid substitution increases both carboxylation turnover number and CO 2 affinity of form II Rubisco [J ] . Biochemical and Biophysical Research Communications , 2025 , 768 : 151940 .

SASCHENBRECKER S , BRACHER A , RAO K V , et al . Structure and function of RbcX, an assembly chaperone for hexadecameric Rubisco [J ] . Cell , 2007 , 129 ( 6 ): 1189 - 1200 .

ZHANG W , SUN L , FAN J . Heterologous assembly of red-type Rubisco and functional identification of chaperonin in Porphyridium purpureum [J ] . Algal Research , 2024 , 79 : 103487 .

TARNAWSKI M , GUBERNATOR B , KOLESINSKI P , et al . Heterologous expression and initial characterization of recombinant RbcX protein from Thermosynechococcus elongatus BP-1 and the role of RbcX in RuBisCO assembly [J ] . Acta Biochimica Polonica , 2008 , 55 ( 4 ): 777 - 785 .

KALIMUTHU P , HAKOPIAN S , NIKS D , et al . The Reversible Electrochemical Interconversion of Formate and CO 2 by Formate Dehydrogenase from Cupriavidus necator [J ] . The Journal of Physical Chemistry B , 2023 , 127 ( 39 ): 8382 - 8392 .

SAHIN S , LEMAIRE O N , BELHAMRI M , et al . Bioelectrocatalytic CO 2 Reduction by Mo-Dependent Formylmethanofuran Dehydrogenase [J ] . Angewandte Chemie International Edition , 2023 , 62 ( 45 ): e202311981 .

LAI C , SHIM W Y , LI J , et al . Biocatalytic conversion of CO 2 to value-added chemicals using hybrid protein scaffolds [J ] . Chemical Engineering Journal , 2025 , 520 : 166023 .

WU R , LI F , CUI X , et al . Enzymatic Electrosynthesis of Glycine from CO 2 and NH3 [J ] . Angewandte Chemie International Edition , 2023 , 62 ( 14 ): e202218387 .

PANICH J , TOPPARI E , TEJEDOR-SANZ S , et al . Functional plasticity of HCO3- uptake and CO 2 fixation in Cupriavidus necator H16 [J ] . Bioresource Technology , 2024 , 410 : 131214 .

ZHANG J , LIU G , CARVAJAL A I , et al . Discovery of a readily heterologously expressed Rubisco from the deep sea with potential for CO 2 capture [J ] . Bioresources and Bioprocessing , 2021 , 8 ( 1 ): 86 .

JESPERSEN M G , VANGSGAARD E F , SAAVEDRA M A , et al . Comparative Genomic Assessment of the Cupriavidus necator Species for One-Carbon Based Biomanufacturin g [J ] . Microbial Biotechnology , 2025 , 18 ( 7 ): e70201 .

SHIN J , BAE J , LEE H , et al . Genome-wide CRISPRi screen identifies enhanced autolithotrophic phenotypes in acetogenic bacterium Eubacterium limosum [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2023 , 120 ( 6 ): e2216244120 .

LI J , ZHANG L Y , XU Q , et al . CRISPR-Cas9 Toolkit for Genome Editing in an Autotrophic CO 2 -Fixing Methanogenic Archaeon [J ] . Microbiology Spectrum , 2022 , 10 ( 4 ): e01165-22 .

MYERS T , DYKSTRA C M . Teaching old dogs new tricks: genetic engineering methanogens [J ] . Applied and Environmental Microbiology , 2024 , 90 ( 7 ): e02247-23 .

VAJENTE M , CLERICI R , BALLERSTEDT H , et al . Using Cupriavidus necator H16 to Provide a Roadmap for Increasing Electroporation Efficiency in Nonmodel Bacteria [J ] . ACS Synthetic Biology , 2025 , 14 ( 11 ): 4330 - 4341 .

WELDON M , EULER C . Physiology-informed use of Cupriavidus necator in biomanufacturing: a review of advances and challenges [J ] . Microbial Cell Factories , 2025 , 24 ( 1 ): 30 .

IGBOJIONU L I , MARTINEZ M M , GODDARD A D , et al . Whole-cell biotechnological applications with thermoacidophilic Crenarchaeota : Opportunities and challenges [J ] . Process Biochemistry , 2026 , 160 : 86 - 101 .

ORTHOFER M , HOFMANN W , RITTMANN S K R , et al . A high-pressure bioreactor system for the cultivation of Methanothermobacter marburgensis on advanced growth media for sustainable energy applications [J ] . Scientific Reports , 2025 , 15 ( 1 ): 35519 .

PUIMAN L , BOKELMANN C , SIMPSON S D , et al . Dos and don'ts for scaling up gas fermentations [J ] . Current Opinion in Biotechnology , 2025 , 93 : 103294 .

BALTSAVIA I , STAMOULOS G , TZIAVARAS K , et al . MjCyc: Rediscovering the pathway-genome landscape of the first sequenced archaeon, Methanocaldococcus (Methanococcus) jannaschii [J ] . iScience , 2025 , 28 ( 1 ): 111546 .

HUMPHREYS C M , MCLEAN S , SCHATSCHNEIDER S , et al . Whole genome sequence and manual annotation of Clostridium autoethanogenum , an industrially relevant bacterium [J ] . BMC Genomics , 2015 , 16 : 1085 .

JAHN M , CRANG N , GYNNÅ A H , et al . The energy metabolism of Cupriavidus necator in different trophic conditions [J ] . Applied and Environmental Microbiology , 2024 , 90 ( 10 ): e00748-24 .

ZHANG Z , YANG F , LIU Y , et al . Transposon insertion sequencing identifies novel genes involved in product synthesis in gas-fermenting Clostridium ljungdahlii [J ] . Synthetic and Systems Biotechnology , 2026 , 14 : 180 - 191 .

CAIVANO A , VAN WINDEN W , DRAGONE G , et al . Enzyme-constrained metabolic model and in silico metabolic engineering of Clostridium ljungdahlii for the development of sustainable production processes [J ] . Computational and Structural Biotechnology Journal , 2023 , 21 : 4634 - 4646 .

PEARCY N , GARAVAGLIA M , MILLAT T , et al . A genome-scale metabolic model of Cupriavidus necator H16 integrated with TraDIS and transcriptomic data reveals metabolic insights for biotechnological applications [J ] . PLOS Computational Biology , 2022 , 18 ( 5 ): e1010106 .

NAGARAJAN H , SAHIN M , NOGALES J , et al . Characterizing acetogenic metabolism using a genome-scale metabolic reconstruction of Clostridium ljungdahlii [J ] . Microbial Cell Factories , 2013 , 12 : 118 .

EMERSON D F , WOOLSTON B M , LIU N , et al . Enhancing H 2 -dependent growth of and CO 2 fixation by Clostridium ljungdahlii through nitrate supplementation [J ] . Biotechnology and Bioengineering , 2019 , 116 ( 2 ): 294 - 306 .

KITA A , IWASAKI Y , SAKAI S , et al . Development of genetic transformation and heterologous expression system in carboxydotrophic thermophilic acetogen Moorella thermoacetica [J ] . Journal of Bioscience and Bioengineering , 2013 , 115 ( 4 ): 347 - 352 .

TREMBLAY P-L , ZHANG T . Genetic tools for the electrotroph Sporomusa ovata and autotrophic biosynthesis [J ] . Applied and Environmental Microbiology , 2024 , 90 ( 1 ): e01757-23 .

WOODS C , HUMPHREYS C M , RODRIGUES R M , et al . A novel conjugal donor strain for improved DNA transfer into Clostridium spp [J ] . Anaerobe , 2019 , 59 : 184 - 191 .

DELLA VALLE S , ORSI E , CREUTZBURG S C A , et al . Streamlined and efficient genome editing in Cupriavidus necator H16 using an optimised SIBR-Cas system [J ] . Trends in Biotechnology , 2025 , 43 ( 6 ): 1470 - 1491 .

POULALIER-DELAVELLE M , BAKER J P , MILLARD J , et al . Endogenous CRISPR/Cas systems for genome engineering in the acetogens Acetobacterium woodii and Clostridium autoethanogenum [J ] . Frontiers in Bioengineering and Biotechnology , 2023 , 11 : 1213236 .

ZHAO R , LIU Y , ZHANG H , et al . CRISPR-Cas12a-Mediated Gene Deletion and Regulation in Clostridium ljungdahlii and Its Application in Carbon Flux Redirection in Synthesis Gas Fermentation [J ] . ACS Synthetic Biology , 2019 , 8 ( 10 ): 2270 - 2279 .

HUANG H , CHAI C S , LI N , et al . CRISPR/Cas9-based efficient genome editing in Clostridium ljungdahlii , an autotrophic gas-fermenting bacterium [J ] . ACS Synthetic Biology , 2016 , 5 ( 12 ): 1355 - 1361 .

WINDHORST C , GESCHER J . Efficient biochemical production of acetoin from carbon dioxide using Cupriavidus necator H16 [J ] . Biotechnology for Biofuels , 2019 , 12 : 163 .

WEILER J R , JURGENSEN N , CORNEJO INFANTE M , et al . Strain and model development for auto- and heterotrophic 2,3-butanediol production using Cupriavidus necator H16 [J ] . Biotechnology for Biofuels and Bioproducts , 2024 , 17 ( 1 ): 108 .

SALINAS A , MCGREGOR C , IRORERE V , et al . Metabolic engineering of Cupriavidus necator H16 for heterotrophic and autotrophic production of 3-hydroxypropionic acid [J ] . Metabolic Engineering , 2022 , 74 : 178 - 190 .

GASCOYNE J L , BOMMAREDDY R R , HEEB S , et al . Engineering Cupriavidus necator H16 for the autotrophic production of (R) -1,3-butanediol [J ] . Metabolic Engineering , 2021 , 67 : 262 - 276 .

WEN Z Q , LI Y Z , SU H J , et al . Deletion of electron-bifurcating [FeFe ] -hydrogenase enhances H 2 -driven CO 2 fixation and ethanol production in Clostridium ljungdahlii [J ] . Bioresource Technology , 2026 , 453 : 134636 .

TANG R , WENG C , PENG X , et al . Metabolic engineering of Cupriavidus necator H16 for improved chemoautotrophic growth and PHB production under oxygen-limiting conditions [J ] . Metabolic Engineering , 2020 , 61 : 11 - 23 .

HEFFERNAN J K , LAI C-Y , GONZALEZ-GARCIA R A , et al . Biogas upgrading using Clostridium autoethanogenum for value-added products [J ] . Chemical Engineering Journal , 2023 , 452 ( Pt 1 ): 138950 .

NOVAK K , NEUENDORF C S , KOFLER I , et al . Blending industrial blast furnace gas with H 2 enables Acetobacterium woodii to efficiently co-utilize CO, CO 2 and H 2 [J ] . Bioresource Technology , 2021 , 323 : 124573 .

VLAEMINCK E , ACUNA LOPEZ P , UITTERHAEGEN E , et al . Pressure fermentation to boost CO 2 -based poly(3-hydroxybutyrate) production using Cupriavidus necator [J ] . Bioresource Technology , 2024 , 408 : 131162 .

PERRET L , BOUKIS N , SAUER J . Synthesis gas fermentation at high cell density: How pH and hydrogen partial pressure affect productivity and product ratio in continuous fermentation [J ] . Bioresource Technology , 2024 , 391 ( Pt A ): 129894 .

GALLARDO-ATEHORTUA M , SHIVA , AHRING B K . Developing a robust biomethanation process by improving oxygen tolerance of Methanothermobacter wolfeii strain BSEL [J ] . Bioresource Technology , 2026 , 458 : 135041 .

MA J , CUI Y , ZHOU R , et al . Adaptive laboratory evolutionary strategies and mechanisms of Synechococcus elongatu PCC 7942 under high concentration of CO 2 [J ] . Bioresource Technology , 2025 , 434 : 132789 .

SU L , RODRIGUEZ-JIMENEZ S , SHORT M I M , et al . Adapting gas fermenting bacteria for light-driven domino valorization of CO 2 [J ] . Chemical Science , 2025 , 16 ( 26 ): 11801 - 11808 .

INGELMAN H , HEFFERNAN J K , HARRIS A , et al . Autotrophic adaptive laboratory evolution of the acetogen Clostridium autoethanogenum delivers the gas-fermenting strain LAbrini with superior growth, products, and robustness [J ] . New Biotechnology , 2024 , 83 : 1 - 15 .

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非模式微生物在CO2生物转化中的底盘开发潜力与工程化策略

Chassis development potential and engineering strategies for non-model microorganisms in CO2-based biotransformation

DOI：10.12211/2096-8280.2026-103

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非模式微生物在CO₂生物转化中的底盘开发潜力与工程化策略

Chassis development potential and engineering strategies for non-model microorganisms in CO₂-based biotransformation