Advancements in Microbial Cell Engineering for Benzylisoquinoline Alkaloid Production.

Cui-Ying Zhang, Qingqing Ye, Xu Sun, Adison Wong, Jee Loon Foo, Aiqun Yu, Chen Ding, Xiangyu Li, Liyan Cao, Yuyang Wang, Zhuo Li, Chang Liu, Desmond Teo, Mingxin Chang, Yuqing Han, Qingeng Huang

Journal: ACS synthetic biology 2024;13(12):3842-3856

PMID: 39579377

Full Text on American Chemical Society View on PubMed

Abstract

Benzylisoquinoline alkaloids (BIAs) are a class of natural compounds found in plants of the family, known for their diverse pharmacological activities. However, the extraction yields of BIAs from plants are limited, and the cost of chemical synthesis is prohibitively high. Recent advancements in systems metabolic engineering and genomics have made it feasible to use microbes as bioreactors for BIAs production. This review explores recent progress in enhancing the production and yields of BIAs in two microbial systems: and . It covers various BIAs, including ()-reticuline, morphinane, protoberberine, and aporphine alkaloids. The review provides strategies and technologies for BIAs synthesis, analyzes current challenges in BIAs research, and offers recommendations for future research directions.

Address: State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin Key Laboratory of Industrial Microbiology, College of Biotechnology, Tianjin University of Science and Technology, No.29 the 13th Street TEDA, Tianjin 300457, PR China.; Food Chemical and Biotechnology Cluster, Singapore Institute of Technology, Singapore 828608, Singapore.; Qingyuan One Alive Institute of Biological Research Co., Ltd, Qingyuan 500112, PR China.; Synthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore.; NUS Synthetic Biology for Clinical and Technological Innovation (SynCTI), National University of Singapore, Singapore 117456, Singapore.; Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.; National Centre for Engineering Biology (NCEB), 119077Singapore, Singapore.

DOI: 10.1021/acssynbio.4c00599

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https://doi.org/10.1021/acssynbio.4c00599

MeSH Terms: Benzylisoquinolines, Metabolic Engineering, Escherichia coli, Saccharomyces cerevisiae, Alkaloids, Aporphines, Berberine Alkaloids