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Adv. Sci., 27 December 2024 | https://doi.org/10.1002/advs.202412670 Metabolic Engineering of Corynebacterium glutamicum for High-Level Production of 1,5-Pentanediol, a C5 Diol Platform Chemical

Yu Jung Sohn ¹, Se-Yeun Hwang ², Haeyoung Lee ¹, Subeen Jeon ¹, Ji Young Park¹, Jaehyung Kim ³, Donghyuk Kim³, Ki Jun Jeong ⁴, Sang Yup Lee ^5,6, Jeong Chan Joo ⁷, Jin-Byung Park ², Si Jae Park¹

¹Department of Chemical Engineering and Materials Science, Graduate Program in System Health Science and Engineering, Ewha Womans University, Seoul, 03760, Republic of Korea.
²Department of Food Science and Biotechnology, Ewha Womans University, Seoul, 03760, Republic of Korea.
³School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.
⁴Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
⁵Metabolic and Biomolecular Engineering National Research Laboratory, Systems Metabolic Engineering and Systems Healthcare Cross-Generation Collaborative Laboratory, Department of Chemical and Biomolecular Engineering (BK21 four), Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
⁶BioProcess Engineering Research Center, Center for Synthetic Biology, KAIST Institute for the BioCentury, KAIST Institute for Artificial Intelligence, KAIST, Daejeon, 34141, Republic of Korea.
⁷Department of Chemical Engineering, Kyung Hee University, Yongin, 17104, Republic of Korea.

Y.J.S. and S.Y.H. contributed equally to this work.
Corresponding Authors: Jeong Chan Joo, Jin-Byung Park, Si Jae Park

Abstract

The biobased production of chemicals is essential for advancing a sustainable chemical industry. 1,5-Pentanediol (1,5-PDO), a five-carbon diol with considerable industrial relevance, has shown limited microbial production efficiency until now. This study presents the development and optimization of a microbial system to produce 1,5-PDO from glucose in Corynebacterium glutamicum via the l-lysine-derived pathway. Engineering began with creating a strain capable of producing 5-hydroxyvaleric acid (5-HV), a key precursor to 1,5-PDO, by incorporating enzymes from Pseudomonas putida (DavB, DavA, and DavT) and Escherichia coli (YahK). Two conversion pathways for further converting 5-HV to 1,5-PDO are evaluated, with the CoA-independent pathway—utilizing Mycobacterium marinum carboxylic acid reductase (CAR) and E. coli YqhD—proving greater efficiency. Further optimization continues with chromosomal integration of the 5-HV module, increasing 1,5-PDO production to 5.48 g L−1. An additional screening of 13 CARs identifies Mycobacterium avium K-10 (MAP1040) as the most effective, and its engineered M296E mutant further increases production to 23.5 g L−1. A deep-learning analysis reveals that Gluconobacter oxydans GOX1801 resolves the limitations of NADPH, allowing the final strain to produce 43.4 g L−1 1,5-PDO without 5-HV accumulation in fed-batch fermentation. This study demonstrates systematic approaches to optimizing microbial biosynthesis, positioning C. glutamicum as a promising platform for sustainable 1,5-PDO production.

논문정보

형식Research article
게재일2024년 12월 (BRIC 등록일 2024-12-30)
연구진국내 연구진
분야 생명과학 > 생물공학

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