Rational engineering strategies for achieving high-yield,high-quality and high-stability of natural product production in actinomycetes |
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| Institution: | 1. Department of Chemistry, Hiyoshi Campus, Keio University, Kohoku-ku, Yokohama 223-8521, Japan;2. Laboratory of Microbial Engineering, Ōmura Satoshi Memorial Institute, Kitasato University, Sagamihara, Kanagawa 252-0373, Japan;1. The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kogle Alle 6, Hørsholm, Denmark;2. Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA;3. Metabolic and Biomolecular Engineering National Research Laboratory, Department of Chemical and Biomolecular Engineering (BK21 Plus Program), Center for Systems and Synthetic Biotechnology, Institute for the BioCentury, BioInformatics Research Center, and BioProcess Engineering Research Center, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea;1. First Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou 310058, China;2. Zhejiang Provincial Key Laboratory for Microbial Biochemistry and Metabolic Engineering, Hangzhou 310058, China;1. Biotechnology Research Center, Southwest University, Chongqing, 400715, China;2. Chongqing Key Laboratory of Plant Resource Conservation and Germplasm Innovation, Southwest University, Chongqing, 400715, China;3. State Cultivation Base of Crop Stress Biology for Southern Mountainous Land, Academy of Agricultural Sciences, Southwest University, Chongqing, 400715, China |
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| Abstract: | Actinomycetes are recognized as excellent producers of microbial natural products, which have a wide range of applications, especially in medicine, agriculture and stockbreeding. The three main indexes of industrialization (titer, purity and stability) must be taken into overall consideration in the manufacturing process of natural products. Over the past decades, synthetic biology techniques have expedited the development of industrially competitive strains with excellent performances. Here, we summarize various rational engineering strategies for upgrading the performance of industrial actinomycetes, which include enhancing the yield of natural products, eliminating the by-products and improving the genetic stability of engineered strains. Furthermore, the current challenges and future perspectives for optimizing the industrial strains more systematically through combinatorial engineering strategies are also discussed. |
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| Keywords: | Microbial natural products Actinomycetes Synthetic biology Strain improvement Industrialization |
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