Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production

Meirong Gao, Yuxin Zhao, Zhanyi Yao, Qianhe Su, Payton Van Beek and Zengyi Shao ()
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Meirong Gao: Iowa State University
Yuxin Zhao: Iowa State University
Zhanyi Yao: Iowa State University
Qianhe Su: Iowa State University
Payton Van Beek: Iowa State University
Zengyi Shao: Iowa State University

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Plant-sourced aromatic amino acid (AAA) derivatives are a vast group of compounds with broad applications. Here, we present the development of a yeast consortium for efficient production of (S)-norcoclaurine, the key precursor for benzylisoquinoline alkaloid biosynthesis. A xylose transporter enables the concurrent mixed-sugar utilization in Scheffersomyces stipitis, which plays a crucial role in enhancing the flux entering the highly regulated shikimate pathway located upstream of AAA biosynthesis. Two quinate permeases isolated from Aspergillus niger facilitates shikimate translocation to the co-cultured Saccharomyces cerevisiae that converts shikimate to (S)-norcoclaurine, resulting in the maximal titer (11.5 mg/L), nearly 110-fold higher than the titer reported for an S. cerevisiae monoculture. Our findings magnify the potential of microbial consortium platforms for the economical de novo synthesis of complex compounds, where pathway modularization and compartmentalization in distinct specialty strains enable effective fine-tuning of long biosynthetic pathways and diminish intermediate buildup, thereby leading to increases in production.

Date: 2023
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DOI: 10.1038/s41467-023-43049-w

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