Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Chlorogenic Acid from Glucose
Authors
Xiao, Feng
Lian, Jiazhang
Tu, Shuai
Xie, Linlin
Li, Jun
Zhang, Fuming
Linhardt, Robert J.
Huang, Haichan
Zhong, Weihong
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2022-02-18
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Chlorogenic Acid from Glucose, F. Xiao, J. Lian, S. Tu, L. Xie, J. Li, F. Zhang, R. J. Linhardt, H. Huang, W. Zhong, ACS Synthetic Biology, 11, 800-811, 2022
Abstract
Chlorogenic acid (CGA), a major dietary phenolic compound, has been increasingly used in the food and pharmaceutical industries because of its ready availability and extensive biological and pharmacological activities. Traditionally, extraction from plants has been the main approach for the commercial production of CGA. This study reports the first efficient microbial production of CGA by engineering the yeast, Saccharomyces cerevisiae, on a simple mineral medium. First, an optimized de novo biosynthetic pathway for CGA was reconstructed in S. cerevisiae from glucose with a CGA titer of 36.6 ± 2.4 mg/L. Then, a multimodule engineering strategy was employed to improve CGA production: (1) unlocking the shikimate pathway and optimizing carbon distribution; (2) optimizing the l-Phe branch and pathway balancing; and (3) increasing the copy number of CGA pathway genes. The combination of these interventions resulted in an about 6.4-fold improvement of CGA titer up to 234.8 ± 11.1 mg/L in shake flask cultures. CGA titers of 806.8 ± 1.7 mg/L were achieved in a 1 L fed-batch fermenter. This study opens a route to effectively produce CGA from glucose in S. cerevisiae and establishes a platform for the biosynthesis of CGA-derived value-added metabolites.
Description
ACS Synthetic Biology, 11, 800-811
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
ACS Synthetic Biology
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
ACS Synthetic Biology
https://harc.rpi.edu/
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https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1021/acssynbio.1c00487