Advances in the biological utilization of one-carbon compounds

LI Jian; CHEN Yun; LIU Haiyan; TAN Zaigao

doi:10.12211/2096-8280.2025-077

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Advances in the biological utilization of one-carbon compounds

Invited Review | 更新时间：2026-07-03

- Advances in the biological utilization of one-carbon compounds
- Synthetic Biology Journal Vol. 7, Issue 3, Pages: 495-513(2026)
- 作者机构：
  
  1. 上海交通大学微生物代谢全国重点实验室，上海 200240
  2.上海交通大学生命科学技术学院生物工程系，上海 200240
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2025-077
  CLC： Q816
- Received：29 July 2025，
  
  Revised：2025-10-10，
  
  Published：30 June 2026
- 稿件说明：
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李健，陈云，刘海艳，谭在高. 一碳化合物生物利用的合成生物学研究进展［J］. 合成生物学， 2026， 7（3）： 495-513

LI Jian， CHEN Yun， LIU Haiyan， TAN Zaigao. Advances in the biological utilization of one-carbon compounds［J］. Synthetic Biology Journal， 2026， 7（3）： 495-513
李健，陈云，刘海艳，谭在高. 一碳化合物生物利用的合成生物学研究进展［J］. 合成生物学， 2026， 7（3）： 495-513 DOI： 10.12211/2096-8280.2025-077.

LI Jian， CHEN Yun， LIU Haiyan， TAN Zaigao. Advances in the biological utilization of one-carbon compounds［J］. Synthetic Biology Journal， 2026， 7（3）： 495-513 DOI： 10.12211/2096-8280.2025-077.

摘要

一碳化合物（C

，包括CO

、CO、甲烷、甲醇及甲酸等）作为重要的含碳资源，凭借其来源广泛、经济及可再生特性，已成为生物制造领域的新型战略原料。近年来，合成生物学与代谢工程技术的突破性进展显著推动了C

化合物的生物转化路径创新，为碳中和目标下的绿色生物制造开辟了新范式。本文聚焦天然C

利用微生物的代谢网络优化、非天然C

利用途径的开发以及人工合成甲基营养菌的理性设计，系统比较评估了不同微生物底盘在C

生物转化中的应用潜力及关键C

同化途径的代谢特征，并综述了2022—2025年间该领域的前沿策略与技术成果。进一步对比分析了甲基营养菌的应用领域，探讨了各类宿主在产物合成中的适配性，探讨了当前存在的生物固碳效率低、人工固碳途径在体内难以高效运行、毒性中间体限制甲醇同化、人工甲基营养菌生长缓慢等难题。在此基础上，进一步讨论了实验室进化、酶工程、人工途径设计等多种手段协同提升C

利用效率的潜力。最后，展望了人工智能在C

生物制造领域发展中的重要驱动作用，主要包括其在基因编辑、底盘细胞优化、酶工程与蛋白质设计以及DBTL循环加速等方面的应用潜力，以期为C

驱动的可持续生物经济体系构建提供理论支撑。

Abstract

One-carbon (C

) compounds—including CO

methane

methanol

and formate—have emerged as strategic feedstocks for next-generation biomanufacturing due to their abundance

economic viability

and renewability. However

the efficient biological conversion of C

substrates into valuable products is hampered by several challenges

including the low intrinsic efficiency of natural carbon fixation pathways

the thermodynamic and kinetic barriers in engineering efficient

de novo

artificial assimilation routes

the cytotoxic effects of reactive intermediates like formaldehyde

and the generally suboptimal industrial environments and slow growth of both native and synthetic C

-util

izing microbes. Recent breakthroughs in synthetic biology and metabolic engineering have substantially mitigated these constraints

thereby accelerating C

bioconversion and establishing a novel paradigm for carbon-neutral and green biomanufacturing. This review systematically examines state-of-the-art strategies and technological milestones reported within the past few years

with a focus on (i) Metabolic rewiring of native C

-utilizing microorganisms to enhance both C

-assimilation efficiency and product-synthesis capacity

(ii)

de novo

design of non-natural C

assimilation pathways to provide more efficient routes for constructing C

-utilizing cell factories

and (iii) engineering artificial C

-utilizing cell factories through reconstituting natural or artificial C

assimilation modules in well-established industrial fermentation strains to establish platforms for C

-based bioproduction. Moving beyond strategy description

we also provide a comparative analysis of the metabolic characteristics

advantages

and limitations of key natural and synthetic C

assimilation pathways

and further evaluate the applicability of various microbial hosts for the synthesis of targeted products ranging from biofuels and bulk chemicals to specialized fine products. A critical discussion addresses persistent technical bottlenecks

such as low activity of key C

assimilation enzymes

poor biomanufacturing capabilities of natural C

-utilizing bacteria

and the challenges in achieving high flux through artificial pathways

in vivo

. Then

we explore the synergistic potential of integrated strategies—combining adaptive laboratory evolution

enzyme engineering

computational modeling

and systems-level analysis—to boost C

utilization. Finally

this review highlights the important role of artificial intelligence in driving the development of C

biomanufacturin

with a focus on its potential applications in gene editing

chassis cell optimization

enzyme engineering

protein design

and DBTL cycle acceleration

aiming to provide theoretical support for the construction of a C

-driven sustainable bioeconomy.

关键词

Keywords

references

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