Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production

SUN Qihang; XU Yuncong; WU Lingrui; RONG Jiale; WANG Yanwen; CAO Yudan; LUO Chen; WU Xuri

doi:10.11665/j.issn.1000-5048.20220612

Journal of China Pharmaceutical University > 2022 > 53(6): 725-733. > DOI: 10.11665/j.issn.1000-5048.20220612

SUN Qihang, XU Yuncong, WU Lingrui, RONG Jiale, WANG Yanwen, CAO Yudan, LUO Chen, WU Xuri. Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production[J]. Journal of China Pharmaceutical University, 2022, 53(6): 725-733. DOI: 10.11665/j.issn.1000-5048.20220612

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Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production

Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81973214)

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Received Date: June 16, 2022
Revised Date: November 22, 2022

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Abstract

Abstract

Nosiheptide is a typical thiopeptide antibiotic displaying potent activity toward various drug-resistant strains of Gram-positive pathogens.Although nosiheptide lacks in vivo activity, and good water-solubility with a series of uncontrollable analogues, which may limit its clinical application, glycosylated analogues may overcome problem of low activity and may improve its druggability.In search of novel glycosylated nosiheptide producers, we applied a genome mining strategy that identified Actinoalloteichus sp.AHMU CJ021 that contains all genes required.However, despite the presence of a predicted glycosyltransferase, glycosylated derivatives of nosiheptide were not detected, after following one strain many compounds (OSMAC) strategy and heterologous expression of a regulatory protein NocP.Nevertheless, nosiheptide produced by this strain was remarkably pure, and further experiments were conducted to improve its production by optimization of the culture medium.Under optimal conditions, 58.73 mg/L nosiheptide was produced, representing an almost 6-fold improvement compared to the original fermentation medium.Therefore, we consider Actinoalloteichus sp.AHMU CJ021 a suitable potential candidate for industrial production of nosiheptide, which provides the basis for solving the problem of nosiheptide structural analogues.
- nosiheptide,
- genome mining,
- fermentation,
- biosynthetic gene cluster,
- glycosyltransferase

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Discovery of a new nosiheptide-producing strain and its fermentation optimization for nosiheptide production

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