Discovery of Three 22-Membered Macrolides by Deciphering the Streamlined Genome of Mangrove-Derived Streptomyces sp. HM190

Ye, Yanghui; Anwar, Nusratgul; Mao, Xu‐Ming; Wu, Shuai; Yan, Cen; Zhao, Zhe; Zhang, Ran; Nie, Yan-Fang; Zhang, Jianwei; Wang, Jidong; Wu, Min

doi:10.3389/fmicb.2020.01464

Cited by 7 publications

(4 citation statements)

References 60 publications

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“…These metabolites were all C-4 epimers based on the julichrome Q 10 184 skeleton. 59 Analysis of various Streptomyces ferments afforded chlorinated 3-phenylpropanoic acid derivatives 188–190 , 60 MMP-1 secretion inhibitor sarmentosamide 191 , 61 a new anti-MRSA tetracene derivative, mersaquinone 192 , 62 hexacyclic xanthone ukixanthomycin A 193 , 63 butenolide mycenolide A 194 , 64 22-membered macrolides 195–197 , 65 angucycline derivatives, monacyclinones G–K 198–202 and ent -gephyromycin A 203 (ref. 66) and chromomycin A9 204 , which showed potent activity towards several microbial strains.…”

Section: Marine Microorganisms and Phytoplanktonmentioning

confidence: 99%

Marine natural products

et al. 2022

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Section: Marine Microorganisms and Phytoplanktonmentioning

confidence: 99%

Marine natural products

et al. 2022

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“…They found that PKS genes S1-S8 were proposed to be responsible for the production of three 22-membered macrolides. A total of 30 biosynthetic gene clusters (BGCs), especially gene cluster 5, were responsible for biosynthesis of the macrolide in a strain-specific 126,331bp genomic island belonging to the left-arm region [36].…”

Section: Biosynthesis Challengesmentioning

confidence: 99%

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis

et al. 2022

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Tuberculosis has become a major health problem globally. This is worsened by the emergence of resistant strains of Mycobacterium tuberculosis showing ability to evade the effectiveness of the current antimycobacterial therapies. Therefore, the efforts carried out to explore new entities from many sources, including marine, are critical. This review summarizes several marine-derived macrolides that show promising activity against M. tuberculosis. We also provide information regarding the biosynthetic processes of marine macrolides, including the challenges that are usually experienced in this process. As most of the studies reporting the antimycobacterial activities of the listed marine macrolides are based on in vitro studies, the future direction should consider expanding the trials to in vivo and clinical trials. In addition, in silico studies should also be explored for a quick screening on marine macrolides with potent activities against mycobacterial infection. To sum up, macrolides derived from marine organisms might become therapeutical options for tackling antimycobacterial resistance of M. tuberculosis.

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“…Interestingly, metabolomics and genomics approaches have proven to be efficient and promising tools for defining phenotypes in a dynamic context, with the potential to reduce rediscovery rates (Khoomrung et al, 2017 ; Pye et al, 2017 ; van Der Hooft et al, 2020 ), and several tools have been designed for this purpose, as reported by Caesar et al ( 2021 ). These approaches have been successfully applied to study the chemical diversity of marine bacteria and to uncover novel bioactive molecules (Macintyre et al, 2014 ; Schneider et al, 2018 ; Ye et al, 2020 ), despite the challenges encountered due to the complexity of biological matrices (Liu and Locasale, 2017 ). More recently, molecular networking, a tandem mass spectrometry (MS/MS) data organizational approach, has been introduced in the field of drug discovery (Wang et al, 2016 ), and the combination of system analyses involving multi-omics data and genome-scale, metabolic network models has greatly contributed to exploring bioactive Actinobacteria (Palazzotto et al, 2019 ) and has great potential to accelerate natural product discovery.…”

Section: Introductionmentioning

confidence: 99%

Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria

et al. 2022

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Multi-omic approaches have recently made big strides toward the effective exploration of microorganisms, accelerating the discovery of new bioactive compounds. We combined metabolomic, molecular networking, and genomic-based approaches to investigate the metabolic potential of the Streptomyces sp. RO-S4 strain isolated from the polluted waters of Bejaia Bay in Algeria. Antagonistic assays against methicillin-resistant Staphylococcus aureus with RO-S4 organic extracts showed an inhibition zone of 20 mm by using the agar diffusion method, and its minimum inhibitory concentration was 16 μg/ml. A molecular network was created using GNPS and annotated through the comparison of MS/MS spectra against several databases. The predominant compounds in the RO-S4 extract belonged to the angucycline family. Three compounds were annotated as known metabolites, while all the others were putatively new to Science. Notably, all compounds had fridamycin-like aglycones, and several of them had a lactonized D ring analogous to that of urdamycin L. The whole genome of Streptomyces RO-S4 was sequenced to identify the biosynthetic gene cluster (BGC) linked to these angucyclines, which yielded a draft genome of 7,497,846 bp with 72.4% G+C content. Subsequently, a genome mining analysis revealed 19 putative biosynthetic gene clusters, including a grincamycin-like BGC with high similarity to that of Streptomyces sp. CZN-748, that was previously reported to also produce mostly open fridamycin-like aglycones. As the ring-opening process leading to these compounds is still not defined, we performed a comparative analysis with other angucycline BGCs and advanced some hypotheses to explain the ring-opening and lactonization, possibly linked to the uncoupling between the activity of GcnE and GcnM homologs in the RO-S4 strain. The combination of metabolomic and genomic approaches greatly improved the interpretation of the metabolic potential of the RO-S4 strain.

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Discovery of Three 22-Membered Macrolides by Deciphering the Streamlined Genome of Mangrove-Derived Streptomyces sp. HM190

Abstract: Discovery of Three 22-Membered Macrolides by Deciphering the Streamlined Genome of Mangrove-Derived Streptomyces sp. HM190.

Cited by 7 publications

References 60 publications

Marine natural products

Marine natural products

Marine Macrolides to Tackle Antimicrobial Resistance of Mycobacterium tuberculosis

Integrated Metabolomic, Molecular Networking, and Genome Mining Analyses Uncover Novel Angucyclines From Streptomyces sp. RO-S4 Strain Isolated From Bejaia Bay, Algeria

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