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)...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-10-01
|
Series: | Antibiotics |
Subjects: | |
Online Access: | https://www.mdpi.com/2079-6382/11/11/1463 |
_version_ | 1827647481239830528 |
---|---|
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. |
first_indexed | 2024-03-09T19:19:43Z |
format | Article |
id | doaj.art-12b89ea7f0334caf8756089ba1b7a355 |
institution | Directory Open Access Journal |
issn | 2079-6382 |
language | English |
last_indexed | 2024-03-09T19:19:43Z |
publishDate | 2022-10-01 |
publisher | MDPI AG |
record_format | Article |
series | Antibiotics |
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 |
work_keys_str_mv | AT dashanzhang genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis AT junbowang genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis AT yongjianqiao genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis AT baixinlin genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis AT zixindeng genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis AT lingxinkong genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis AT delinyou genomeminingandmetabolicprofilingrevealcytotoxiccyclodipeptidesinistreptomyceshygrospinosusivarbeijingensis |