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    Metabolic Engineering of Saccharomyces cerevisiae for High-Level Production of Chlorogenic Acid from Glucose

    Author
    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
    Date Issued
    2022-02-18
    Subject
    Biology; Chemistry and chemical biology; Chemical and biological engineering; Biomedical engineering
    Degree
    Terms of Use
    In Copyright : this Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s). https://rightsstatements.org/page/InC/1.0/;
    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
    Metadata
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    URI
    https://doi.org/10.1021/acssynbio.1c00487; https://hdl.handle.net/20.500.13015/5430
    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.
    Department
    The Linhardt Research Labs.; The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS);
    Relationships
    The Linhardt Research Labs Online Collection; Rensselaer Polytechnic Institute, Troy, NY; ACS Synthetic Biology; https://harc.rpi.edu/;
    Access
    https://login.libproxy.rpi.edu/login?url=https://doi.org/10.1021/acssynbio.1c00487;
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