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

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 transport...

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Main Authors: Meirong Gao, Yuxin Zhao, Zhanyi Yao, Qianhe Su, Payton Van Beek, Zengyi Shao
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-43049-w
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author Meirong Gao
Yuxin Zhao
Zhanyi Yao
Qianhe Su
Payton Van Beek
Zengyi Shao
author_facet Meirong Gao
Yuxin Zhao
Zhanyi Yao
Qianhe Su
Payton Van Beek
Zengyi Shao
author_sort Meirong Gao
collection DOAJ
description 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.
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spelling doaj.art-5c632afb5e39424da3430f63a655bdcf2023-12-03T12:27:19ZengNature PortfolioNature Communications2041-17232023-11-0114111310.1038/s41467-023-43049-wXylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid productionMeirong Gao0Yuxin Zhao1Zhanyi Yao2Qianhe Su3Payton Van Beek4Zengyi Shao5Department of Chemical and Biological Engineering, Iowa State UniversityDepartment of Chemical and Biological Engineering, Iowa State UniversityDepartment of Chemical and Biological Engineering, Iowa State UniversityDepartment of Chemical and Biological Engineering, Iowa State UniversityDepartment of Chemical and Biological Engineering, Iowa State UniversityDepartment of Chemical and Biological Engineering, Iowa State UniversityAbstract 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.https://doi.org/10.1038/s41467-023-43049-w
spellingShingle Meirong Gao
Yuxin Zhao
Zhanyi Yao
Qianhe Su
Payton Van Beek
Zengyi Shao
Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
Nature Communications
title Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
title_full Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
title_fullStr Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
title_full_unstemmed Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
title_short Xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
title_sort xylose and shikimate transporters facilitates microbial consortium as a chassis for benzylisoquinoline alkaloid production
url https://doi.org/10.1038/s41467-023-43049-w
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