NDLI: Identification and Heterologous Expression of the Kendomycin B Biosynthetic Gene Cluster from Verrucosispora sp. SCSIO 07399

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Identification and Heterologous Expression of the Kendomycin B Biosynthetic Gene Cluster from Verrucosispora sp. SCSIO 07399

Content Provider	MDPI
Author	Chen, Jiang Zhang, Shanwen Chen, Yingying Tian, Xinpeng Gu, Yucheng Ju, Jianhua
Copyright Year	2021
Description	Verrucosispora sp. SCSIO 07399, a rare marine-derived actinomycete, produces a set of ansamycin-like polyketides kendomycin B–D (1–3) which possess potent antibacterial activities and moderate tumor cytotoxicity. Structurally, kendomycin B–D contain a unique aliphatic macrocyclic ansa scaffold in which the highly substituted pyran ring is connected to the quinone moiety. In this work, a type I/type III polyketide synthase (PKS) hybrid biosynthetic gene cluster coding for assembly of kendomycin B (kmy), and covering 33 open reading frames, was identified from Verrucosispora sp. SCSIO 07399. The kmy cluster was found to be essential for kendomycin B biosynthesis as verified by gene disruption and heterologous expression. Correspondingly, a biosynthetic pathway was proposed based on bioinformatics, cluster alignments, and previous research. Additionally, the role of type III PKS for generating the precursor unit 3,5-dihydroxybenzoic acid (3,5-DHBA) was demonstrated by chemical complementation, and type I PKS executed the polyketide chain elongation. The kmy cluster was found to contain a positive regulatory gene kmy4 whose regulatory effect was identified using real-time quantitative PCR (RT-qPCR). These advances shed important new insights into kendomycin B biosynthesis and help to set the foundation for further research aimed at understanding and exploiting the carbacylic ansa scaffold.
Starting Page	673
e-ISSN	16603397
DOI	10.3390/md19120673
Journal	Marine drugs
Issue Number	12
Volume Number	19
Language	English
Publisher	MDPI
Publisher Date	2021-11-26
Access Restriction	Open
Subject Keyword	Marine drugs Marine Drugs Kendomycin B Biosynthesis Heterologous Expression Verrucosispora Sp. Scsio 07399
Content Type	Text
Resource Type	Article

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