Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis

Dashan Zhang; Junbo Wang; Yongjian Qiao; Baixin Lin; Zixin Deng; Lingxin Kong; Delin You

doi:10.3390/antibiotics11111463

Antibiotics (Oct 2022)

Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis

Dashan Zhang,
Junbo Wang,
Yongjian Qiao,
Baixin Lin,
Zixin Deng,
Lingxin Kong,
Delin You

Affiliations

Dashan Zhang: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Junbo Wang: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Yongjian Qiao: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Baixin Lin: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Zixin Deng: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Lingxin Kong: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China
Delin You: State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China

DOI: https://doi.org/10.3390/antibiotics11111463
Journal volume & issue: Vol. 11, no. 11
p. 1463

Abstract

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Two new cyclodipeptide (CDP) derivatives (1–2) and another seven known cyclodipeptides (3–9) were isolated from Streptomyces 26D9-414 by the genome mining approach combined with genetic dereplication and the “one strain many compounds” (OSMAC) strategy. The structures of the new CDPs were established on the basis of 1D- and 2D-NMR and comparative electronic circular dichroism (ECD) spectra analysis. The biosynthetic gene clusters (BGCs) for these CDPs were identified through antiSMASH analysis. The relevance between this cdp cluster and the identified nine CDPs was established by genetic interruption manipulation. The newly discovered natural compound 2 displayed comparable cytotoxicity against MDA-MB-231 and SW480 with that of cisplatin, a widely used chemotherapeutic agent for the treatment of various cancers.

Published in Antibiotics

ISSN: 2079-6382 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://www.mdpi.com/journal/antibiotics

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