梭菌属（Clostridium）产乙酸菌代谢工程改造与合成气定向转化研究现状

doi:10.13560/j.cnki.biotech.bull.1985.2025-0283

摘要/Abstract

摘要：

发展微生物固碳技术对于遏制全球气候变暖有重要意义。梭菌属（Clostridium）产乙酸菌能够固定CO₂和CO等一碳气体并将其转化为乙醇等化学产品，从而打破对化石燃料的依赖，是合成气规模化定向转化的潜力菌种。本文综述了梭菌属产乙酸菌的代谢工程改造与合成气定向转化研究现状。首先，对梭菌属产乙酸菌的能量代谢方式进行了解析，阐述了梭菌属产乙酸菌的能量节约机制；其次，对梭菌属产乙酸菌的多种遗传操作工具进行了对比和总结；最后，梳理了当前梭菌属产乙酸菌代谢工程改造两个大方向的前景和存在的问题。总之，本文总结了近年来梭菌属产乙酸菌的代谢工程研究进展，以期为更全面了解该工业微生物的合成气转化潜力提供参考，推动梭菌属产乙酸菌生产可再生能源的平台建设。

关键词: 梭菌属产乙酸菌, 能量节约机制, 代谢工程, 合成气

Abstract:

The development of microbial carbon sequestration technology is crucial for curbing global warming. Acetogenic Clostridium can fix one-carbon gases, such as CO₂ and CO, and convert them into chemical products, such as ethanol, thereby reducing dependence on fossil fuels, which makes acetogenic Clostridium a promising strain for converting syngas into high-value products on a large scale. This review summarizes the research progress in metabolic engineering modifications of acetogenic Clostridium and the directional conversion of syngas. Firstly, the energy metabolism modes of acetogenic Clostridium have been analyzed, and the energy conservation mechanisms of acetogenic Clostridium have been elaborated. Then, various tools for genetic manipulation of acetogenic Clostridium have been compared and summarized. Finally, the current prospects and challenges in the two major directions of metabolic engineering modification of acetogenic Clostridium have been sorted out. In conclusion, this paper summarizes the research progress in metabolic engineering ofacetogenic Clostridium inrecent years, aiming to provide references for more comprehensive understanding of its syngas conversion potential, and promote the development of renewable energy production platform using industrial acetogenic Clostridium.

Key words: acetogenic Clostridium, energy conservation mechanism, metabolic engineering, syngas

刘修平, 朱星宇, 汪光义. 梭菌属（Clostridium）产乙酸菌代谢工程改造与合成气定向转化研究现状[J]. 生物技术通报, doi: 10.13560/j.cnki.biotech.bull.1985.2025-0283.

LIU Xiu-ping, ZHU Xing-yu, WANG Guang-yi. Research Progress in Metabolic Engineering for Modification and Syngas-directed Conversion by Acetogenic Clostridium[J]. Biotechnology Bulletin, doi: 10.13560/j.cnki.biotech.bull.1985.2025-0283.

图/表 3

图1 Wood-Ljungdahl途径Fdh：甲酸脱氢酶；Fhs：甲酰-四氢叶酸合成酶；FTC：甲酰四氢呋喃环水解酶；MTDH：亚甲基四氢呋喃脱氢酶；MetF：亚甲基四氢呋喃还原酶；MetR：甲基转移酶；CODH/ACS：一氧化碳脱氢酶/乙酰辅酶A合酶复合体；Ald：醛脱氢酶；AdhE：醇醛脱氢酶；Pta：磷酸乙酰转移酶；Ack：乙酸激酶；Aor：醛：铁氧还蛋白氧化还原酶

Fig. 1 Wood-Ljungdahl pathwayFdh: Formate dehydrogenase; Fhs: formyl-THF synthetase; FTC: formyl-THF cyclohydrolase; MTDH: methylene-THF dehydrogenase; MetF: methylene-THF reductase; MetR: methyltransferase; CODH/ACS: carbon monoxide dehydrogenase/acetyl-CoA synthase; Ald: acetaldehyde dehydrogenase; AdhE: acetaldehyde/alcohol dehydrogenase; Pta: phosphotransacetylase; Ack: acetate kinase; Aor: aldehyde: ferredoxin oxidoreductase

图2 梭菌属产乙酸菌能量代谢机制

Fig. 2 Energy metabolism mechanism in Acetogenic Clostridium

图3 梭菌属产乙酸菌合成产物的代谢途径ThlA/Thl2：硫解酶；Hbd/Hbd2：3-羟基丁酸辅酶A脱氢酶；Crt/Crt2：巴豆酸酶；Bcd/Bcd2：丁酰辅酶A脱氢酶；AdhE：醇醛脱氢酶；ATF1：乙醇酰转移酶；Ptb/Ptf2：磷酸乙酰转移酶；Buk：丁酸激酶；SAAT：草莓酒精酰转移酶；ETH1：酵母酯合成/水解酶I；MvaS/E：羟甲基戊二酰辅酶A合酶；Idi：异戊二烯焦磷酸异构酶；IspS：异戊二烯合酶；CtfAB：辅酶A亚基A/B转移酶；Adc：乙酰乙酸脱羧酶；Sadh：伯/仲醇脱氢酶；bdhA：3-羟基丁酸脱氢酶；Pta：磷酸乙酰转移酶；Ack：乙酸激酶；Ald：乙醛脱氢酶；Aor：醛氧化还原酶；Etf：电子转移黄素蛋白；Fak：脂肪酸激酶；AldH：己醛脱氢酶；Adh：醇脱氢酶；PFOR：丙酮酸铁氧还蛋白氧化还原酶；AlsS：乙酰乳酸合酶；AldC：乙偶姻脱羧酶；2，3-Bdh：2，3-丁二醇脱氢酶；Ldh：乳酸脱氢酶；PhaC：多羟基烷酸合酶

Fig. 3 Metabolic pathways of synthetic products in Acetogenic ClostridiumThlA/Thl2: Thiolase; Hbd/Hbd2: 3-hydroxybutyryl-CoA dehydrogenase; Crt/Crt2: crotonase; Bcd/Bcd2: butyryl-CoA dehydrogenase; AdhE: acetaldehyde/alcohol dehydrogenase; ATF1: alcohol Acetyltransferase; Ptb/Ptf2: Phosphotransferase; Buk: butyrate kinase; SAAT: strawberry Alcohol Acyltransferase; ETH1: ethanol hexanoyltransferase I; MvaS/E: hydroxymethylglutaryl-CoA synthase/reductase; Idi: isopentenyl pyrophosphate isomerase; IspS: isoprene synthase; CtfAB: acetoacetyl-CoA:acetate/butyrate-CoA transferase; Adc: acetoacetate decarboxylase; Sadh: secondary alcohol dehydrogenase; bdhA: 3-hydroxybutyrate dehydrogenase; Pta: Phosphotransacetylase; Ack: Acetate kinase; Ald: Acetaldehyde dehydrogenase; Aor: aldehyde: ferredoxin oxidoreductase; Etf: electron transfer flavoprotein; Fak: fatty acid kinase; AldH: aldehyde dehydrogenasel; Adh: alcohol dehydrogenase; PFOR: pyruvate: ferredoxin oxidoreductase; AlsS: acetolactate synthase; AldC: acetoin decarboxylase; 2,3-Bdh: 2,3-butanediol dehydrogenase; Ldh: lactate dehydrogenase; PhaC: Polyhydroxyalkanoate Synthase

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