Production of the antidepressant orcinol glucoside in Yarrowia lipolytica with yields over 6,400-fold higher than plant extraction
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Published:2023-06-06
Issue:6
Volume:21
Page:e3002131
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ISSN:1545-7885
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Container-title:PLOS Biology
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language:en
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Short-container-title:PLoS Biol
Author:
Chen Bihuan,
Liu Xiaonan,
Wang Yina,
Bai Jie,
Liu Xiangyu,
Xiang Guisheng,
Liu Wei,
Zhu Xiaoxi,
Cheng Jian,
Lu Lina,
Zhang Guanghui,
Zhang Ge,
Dai Zongjie,
Zi Shuhui,
Yang Shengchao,
Jiang HuifengORCID
Abstract
Orcinol glucoside (OG), mainly found in the rhizome of the traditional Chinese herb Curculigo orchioides Gaertn, is noted for its antidepressant effects. In this study, an efficient screening pipeline was established for identifying the highly active orcinol synthase (ORS) and UDP-dependent glycosyltransferase (UGT) involved in the biosynthesis of OG by combining transcriptome analysis, structure-based virtual screening, and in vitro enzyme activity assays. By enhancing the downstream pathway, metabolic engineering and fermentation optimization, the OG production in Yarrowia lipolytica was improved 100-fold, resulting in a final yield of 43.46 g/L (0.84 g/g DCW), which is almost 6,400-fold higher than the extraction yield from C. orchioides roots. This study provides a reference for rapid identification of functional genes and high-yield production of natural products.
Funder
the Major Science and Technology Projects in Yunnan Province
the Science and Technology Innovation Team of Yunnan
the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory
the Major Science and Technology Programs in Yunnan Province
the Tianjin Science Fund for Distinguished Young Scholars
Science and Technology Partnership Program, Ministry of Science and Technology of China
COMSATS Joint Center for Industrial Biotechnology
National Key R&D Program of China
Publisher
Public Library of Science (PLoS)
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience
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