巴氏梭菌作为工业底盘细胞高效生产1，3-丙二醇——从代谢工程和菌种进化到过程工程和产品分离

刘建明; 张炽坚; 张冰; 曾安平

doi:10.12211/2096-8280.2024-030

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巴氏梭菌作为工业底盘细胞高效生产1，3-丙二醇——从代谢工程和菌种进化到过程工程和产品分离

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- 巴氏梭菌作为工业底盘细胞高效生产1，3-丙二醇——从代谢工程和菌种进化到过程工程和产品分离
- Clostridium pasteurianum as an industrial chassis for efficient production of 1,3-propanediol: from metabolic engineering to fermentation and product separation
- 合成生物学 2024年5卷第6期页码：1386-1403
- 作者机构：
  
  1.西湖大学合成生物学与生物智造中心，浙江杭州 310030
  2.西湖大学工学院，浙江杭州 310030
  3.浙江省全省智能低碳生物合成重点实验室，浙江杭州 310030
  4.西湖大学未来产业研究中心，浙江杭州 310030
  5.广东恒碳科技有限公司，广东广州 510630
- 作者简介：
  
  [ "刘建明（1985—），男，研究员。研究方向为合成生物学，低碳生物制造，代谢工程等。 E-mail：liujianming@westlake.edu.cn" ]
  [ "曾安平（1963—），男，讲席教授，博士生导师，德国工程院院士，西湖大学合成生物学与生物智造中心创始主任。研究方向为生物化工、合成生物学、新型催化软物质和功能材料等。 E-mail：zenganping@westlake.edu.cn" ]
- 基金信息：
  
  国家重点研发计划(2023YFA09014003)
- DOI：10.12211/2096-8280.2024-030
  中图分类号： Q816
- 收稿：2024-03-27，
  
  修回：2024-06-18，
  
  纸质出版：2024-12-31
- 稿件说明：
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刘建明，张炽坚，张冰，曾安平. 巴氏梭菌作为工业底盘细胞高效生产1，3-丙二醇——从代谢工程和菌种进化到过程工程和产品分离［J］. 合成生物学， 2024， 5（6）： 1386-1403

LIU Jianming， ZHANG Chijian， ZHANG Bing， ZENG Anping. Clostridium pasteurianum as an industrial chassis for efficient production of 1，3-propanediol： from metabolic engineering to fermentation and product separation［J］. Synthetic Biology Journal， 2024， 5（6）： 1386-1403
刘建明，张炽坚，张冰，曾安平. 巴氏梭菌作为工业底盘细胞高效生产1，3-丙二醇——从代谢工程和菌种进化到过程工程和产品分离［J］. 合成生物学， 2024， 5（6）： 1386-1403 DOI： 10.12211/2096-8280.2024-030.

LIU Jianming， ZHANG Chijian， ZHANG Bing， ZENG Anping. Clostridium pasteurianum as an industrial chassis for efficient production of 1，3-propanediol： from metabolic engineering to fermentation and product separation［J］. Synthetic Biology Journal， 2024， 5（6）： 1386-1403 DOI： 10.12211/2096-8280.2024-030.

摘要

1，3-丙二醇（PDO）是一种重要的化工原料，广泛应用于材料和化妆品等领域。生物制造PDO具有原料可再生性和环境友好性等众多优点和广阔的发展前景。由于巴氏梭菌（

Clostridium pasteurianum

）菌株安全、非致病、代谢甘油速率快、生长快、不依赖昂贵的培养基组分、天然具备高效生产PDO代谢途径等条件，利用和改造巴氏梭菌作为工业底盘生产PDO呈现出得天独厚的优势。本文首先回顾了PDO的生物制造现状和挑战，随后深入探讨了采用巴氏梭菌生产PDO的方法，特别关注于巴氏梭菌的甘油代谢机制、甘油发酵的策略和发酵过程的工艺设计。值得一提的是，本文作者研究团队筛选到的巴氏梭菌突变体和随之开发的鲁棒性发酵工艺在一定程度上突破了传统巴氏梭菌对环境的要求，特别是对铁离子浓度的敏感性；在电辅助甘油发酵过程中，PDO产量达到120.7 g/L，生产强度达到4.8 g/（L·h），收率达到理论值；并进一步阐述了巴氏梭菌基因工程改造方面的天然屏障，围绕着理性基因组改造和定向进化等几个方面进行了详细讨论；由于PDO产品纯度（

99.9%）通常有较高要求，因此开发高效的下游处理技术对于实现利用可再生资源发酵生产PDO的工业化应用至关重要，本文在分离工艺方面主要讨论了基于蒸发和蒸馏的PDO纯化技术以及基于萃取的PDO纯化技术。通过对代谢工程、菌种进化、发酵过程优化以及产品分离等多个维度全方位分析，全面地解析了巴氏梭菌生产PDO的特点和优势，以及巴氏梭菌作为新型工业底盘微生物在未来发展过程中值得关注的问题。

Abstract

3-Propanediol (PDO) is an important chemical extensively used in material science and the cosmetics industry. The biomanufacturing of PDO offers numerous advantages

such as the renewability of raw materials and environmental friendliness. Among various microorganisms

Clostridium pasteurianum

emerges as an ideal choice for industrial PDO production due to its safety

non-pathogenic nature

rapid glycerol metabolism

fast growth rate

independence from expensive culture medium components

and its inherent efficient metabolic pathway for PDO production. This review begins by introducing the current state and challenges of PDO biomanufacturing

followed by an in-depth discussion of the methods for producing PDO using

C. pasteurianum

. Special attention is paid to the glycerol metabolism mechanism

strategies for glycerol fermentation

and the design of the fermentation process. Notably

our research group has identified

C. pasteurianum

mutant strains and developed robust processes that have largely addressed the organism’s traditional sensitivities to e

nvironmental conditions

especially regarding iron concentration and impurities of raw glycerol. In an electricity-aided fermentation process

PDO concentration as high as 120.6 g/L was achieved

with a productivity of 4.8 g/(L·h) and a yield reaching the theoretical maximum. We further discuss the natural limitations of genetic engineering in

C. pasteurianum

exploring strategies based on rational genomic modification and directed evolution. Finally

the development of efficient downstream processing technologies is emphasized as crucial for realizing the cost-effective microbial production of PDO from renewable resources

since the industrial application of PDO requires a very high purity (

99.9%). The discussion on PDO downstream processing mainly focuses on evaporation

distillation

and extraction-based purification techniques. Through a comprehensive coverage of metabolic engineering

strain evolution

fermentation optimization

and product separation technologies

this review discusses about the characteristics and advantages of PDO production from

C. pasteurianum

highlighting key considerations for advancing this microorganism as a new industrial chassis.

关键词

Keywords

references

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