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Production of 1,4-butanediol through Clostridia C4 pathways

文献类型： 外文期刊

作者： Zha, Mingwei 1 ; Gu, Jiangxin 1 ; Chen, Jian 1 ; Zhang, Huifang 1 ; Li, Mengting 1 ; Chen, Yong 1 ; Niu, Huanqing 1 ; Zhu, Chenjie 1 ; Guo, Ting 2 ; Wang, Zhenyu 1 ; Liu, Dong 1 ; Ying, Hanjie 1 ;

作者机构： 1.Nanjing Tech Univ, Coll Biotechnol & Pharmaceut Engn, 30 Puzhu South Rd, Nanjing 211816, Peoples R China

2.Jiangsu Acad Agr Sci, Nanjing, Peoples R China

关键词： 1,4-butanediol; 4-hydroxybutyryl-CoA dehydratase; reverse beta-oxidation; Clostridium acetobutylicum

期刊名称：BIOTECHNOLOGY & BIOTECHNOLOGICAL EQUIPMENT （ 影响因子：1.4； 五年影响因子：1.7 ）

ISSN： 1310-2818

年卷期： 2024 年 38 卷 1 期

页码：

收录情况： SCI

摘要： 1,4-butanediol (1,4-BDO) is an important building block in the chemical industry that has been mainly produced from fossil fuels, but now biosynthesis of 1,4-BDO has received more and more attention due to environmental issues. The Clostridia C4 pathway produces an intermediate crotonyl-CoA which could be diverted to 1,4-BDO by 4-hydroxybutyryl-CoA dehydratase (4HBD). Here, we compared this pathway with other 1,4-BDO biosynthesis pathways and illustrated its potential advantages regarding cellular energy conservation and theoretical yield. Then, the feasibility of 1,4-BDO production in this way was tested by introducing a single 4HBD in Clostridium acetobutylicum that natively produced the C4 intermediate and a variety of aldehyde/alcohol dehydrogenases (AdhE). Five different 4HBD genes were screened and the Cbei-2100 gene from Clostridium beijerinckii was the most effective, producing 0.066 mg/mL of 1,4-BDO. To block the metabolic flux towards the main product butanol, disruption of butyryl-CoA dehydrogenase (Bcd) was tried but failed, while inactivation of its homologue (FAD/FMN-containing dehydrogenase, Fcd) obtained little effect. Alternatively, the electron-transferring flavoprotein EtfA coupled with Bcd was inactivated, and 1,4-BDO production was greatly increased to 0.182 mg/mL. In conclusion, this study demonstrated the feasibility of 1,4-BDO production through the Clostridia C4 pathway. Further blocking of the competing flux towards butanol would be effective to improve the production of in the future.

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