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

Two new cyclodipeptide (CDP) derivatives (<b>1–2</b>) and another seven known cyclodipeptides (<b>3–9</b>) were isolated from <i>Streptomyces</i> 26D9-414 by the genome mining approach combined with genetic dereplication and the “one strain many compounds” (OSMAC)...

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Main Authors: Dashan Zhang, Junbo Wang, Yongjian Qiao, Baixin Lin, Zixin Deng, Lingxin Kong, Delin You
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:Antibiotics
Subjects:
Online Access:https://www.mdpi.com/2079-6382/11/11/1463
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author Dashan Zhang
Junbo Wang
Yongjian Qiao
Baixin Lin
Zixin Deng
Lingxin Kong
Delin You
author_facet Dashan Zhang
Junbo Wang
Yongjian Qiao
Baixin Lin
Zixin Deng
Lingxin Kong
Delin You
author_sort Dashan Zhang
collection DOAJ
description Two new cyclodipeptide (CDP) derivatives (<b>1–2</b>) and another seven known cyclodipeptides (<b>3–9</b>) were isolated from <i>Streptomyces</i> 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 <i>cdp</i> cluster and the identified nine CDPs was established by genetic interruption manipulation. The newly discovered natural compound <b>2</b> displayed comparable cytotoxicity against MDA-MB-231 and SW480 with that of cisplatin, a widely used chemotherapeutic agent for the treatment of various cancers.
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spelling doaj.art-12b89ea7f0334caf8756089ba1b7a3552023-11-24T03:26:46ZengMDPI AGAntibiotics2079-63822022-10-011111146310.3390/antibiotics11111463Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. BeijingensisDashan Zhang0Junbo Wang1Yongjian Qiao2Baixin Lin3Zixin Deng4Lingxin Kong5Delin You6State 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaState 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, ChinaTwo new cyclodipeptide (CDP) derivatives (<b>1–2</b>) and another seven known cyclodipeptides (<b>3–9</b>) were isolated from <i>Streptomyces</i> 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 <i>cdp</i> cluster and the identified nine CDPs was established by genetic interruption manipulation. The newly discovered natural compound <b>2</b> displayed comparable cytotoxicity against MDA-MB-231 and SW480 with that of cisplatin, a widely used chemotherapeutic agent for the treatment of various cancers.https://www.mdpi.com/2079-6382/11/11/1463genome mininggenetic dereplicationcyclodipeptideOSMACcytotoxicity<i>Streptomyces</i>
spellingShingle Dashan Zhang
Junbo Wang
Yongjian Qiao
Baixin Lin
Zixin Deng
Lingxin Kong
Delin You
Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis
Antibiotics
genome mining
genetic dereplication
cyclodipeptide
OSMAC
cytotoxicity
<i>Streptomyces</i>
title Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis
title_full Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis
title_fullStr Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis
title_full_unstemmed Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis
title_short Genome Mining and Metabolic Profiling Reveal Cytotoxic Cyclodipeptides in <i>Streptomyces hygrospinosus</i> var. Beijingensis
title_sort genome mining and metabolic profiling reveal cytotoxic cyclodipeptides in i streptomyces hygrospinosus i var beijingensis
topic genome mining
genetic dereplication
cyclodipeptide
OSMAC
cytotoxicity
<i>Streptomyces</i>
url https://www.mdpi.com/2079-6382/11/11/1463
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