文献类型：期刊文献

英文题名：Systematic development of a highly efficient cell factory for 5-aminolevulinic acid production

作者：Zhou, Houming[1,2];Zhang, Chengyu[1,2];Li, Zilong[2];Xia, Menglei[3];Li, Zhenghong[1,2];Wang, Zhengduo[1,2];Tan, Gao-Yi[1];Luo, Ying[2];Zhang, Lixin[1];Wang, Weishan[2]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing 100101, Peoples R China;[3]Tianjin Univ Sci & Technol, Coll Biotechnol, Metab & Fermentat Proc Control, Minist Educ, Tianjin 300457, Peoples R China

年份：2024

卷号：42

期号：11

起止页码：1479

外文期刊名：TRENDS IN BIOTECHNOLOGY

收录：;EI(收录号：20243316863085);WOS:【SCI-EXPANDED(收录号:WOS:001359151000001)】；

基金：Acknowledgments This work was supported by the National Key Research and Development Program of China (2020YFA0907800) ; the Na-tional Natural Science Foundation of China (32170095 and 32100066) ; and the Youth Innovation Promotion Association CAS (Y202027) to W.W.

语种：英文

外文关键词：Agriculture - Metabolic engineering - Metabolism

摘要：The versatile applications of 5-aminolevulinic acid (5-ALA) across the fields of agriculture, livestock, and medicine necessitate a cost-efficient biomanufacturing process. In this study, we achieved the economic viability of biomanufacturing this compound through a systematic engineering framework. First, we obtained a 5-ALA synthase (ALAS) with superior performance by exploring its natural diversity with divergent evolution. Subsequently, using a genomescale model, we identified and modified four key targets from distinct pathways in Escherichia coli, resulting in a final enhancement of 5-ALA titers up to 21.82 g/l in a 5-l bioreactor. Furthermore, recognizing that an imbalance of redox equivalents hindered further titer improvement, we developed a dynamic control system that effectively balances redox status and carbon flux. Ultimately, we collaboratively optimized the artificial redox homeostasis system at the transcription level with other cofactors at the feeding level, demonstrating the highest recorded performance to date with a titer of 63.39 g/l for the biomanufacturing of 5-ALA.