Abstract
Employing a genome mining approach, this work aimed to further explore the secondary metabolism associated genes of Streptomyces sp. BRB081, a marine isolate. The genomic DNA of BRB081 was sequenced and assembled in a synteny-based pipeline for biosynthetic gene clusters (BGCs) annotation. A total of 27 BGCs were annotated, including a sibiromycin complete cluster, a bioactive compound with potent antitumor activity. The production of sibiromycin, a pyrrolobenzodiazepine, was confirmed by the analysis of obtained BRB081 extract by HPLC–MS/MS, which showed the presence of the sibiromycin ions themselves, as well as its imine and methoxylated forms. To verify the presence of this cluster in other genomes available in public databases, a genome neighborhood network (GNN) was constructed with the non-ribosomal peptide synthetase (NRPS) gene from Streptomyces sp. BRB081. Although the literature does not report the occurrence of the sibiromycin BGC in any other microorganism than Streptosporangium sibiricum, we have located this BGC in 10 other genomes besides the BRB081 isolate, all of them belonging to the Actinomycetia class. These findings strengthen the importance of uninterrupted research for new producer strains of secondary metabolites with uncommon biological activities. These results reinforced the accuracy and robustness of genomics in the screening of natural products. Furthermore, the unprecedented nature of this discovery confirms the unknown metabolic potential of the Actinobacteria phylum and the importance of continuing screening studies in this taxon.
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Acknowledgements
This study is registered in the Sistema Nacional de Gestão do Patrimônio Genético e do Conhecimento Tradicional Associado (SisGen # A0031D5) within the Brazilian Environmental Ministry, and has been authorized by Instituto Florestal, within the São Paulo State Environmental Secretary (process # 260108 – 004.258/2018).
Funding
This research was supported by São Paulo Research Foundation (FAPESP) grants 2017/16606-6 and 2015/17177-6, CAPES (Finance Code 001, Brazil), and Pró-Reitoria de Pesquisa da USP (PIPAE 2021.1.10424.1.9). L.V.C.L. and M.J.P.F were funded by a fellowship from Conselho Nacional de Desenvolvimento Científico e Tecnológico—CNPq. V.M.B.L. were funded by a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—CAPES.
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Accession numbers: This whole genome shotgun sequencing project of Streptomyces sp. BRB081 is available from GenBank under the accession JACVQE000000000.2. This project can be accessed directly through the link (https://www.ncbi.nlm.nih.gov/nuccore/JACVQE000000000.2/).
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Leite, V.M.B., Garrido, L.M., Tangerina, M.M.P. et al. Genome mining of Streptomyces sp. BRB081 reveals the production of the antitumor pyrrolobenzodiazepine sibiromycin. 3 Biotech 12, 249 (2022). https://doi.org/10.1007/s13205-022-03305-0
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DOI: https://doi.org/10.1007/s13205-022-03305-0