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    Genomics and metabolomics-based assessment of the biosynthetic potential of the sponge-associated microorganism Streptomyces cacaoi strain R2A-843A from the Philippines
    Malto, Zabrina Bernice L.; Reyes, Joeriggo M.; Lo, Bernard Isaiah; Davis, Kevin Bossie S.; Concepcion, Gisela; Salvador-Reyes, Lilibeth A. (Philippine-American Academy of Science and Engineering, 2023-10-20)
    The biosynthetic machinery of the sponge-associated Streptomyces cacaoi strain R2A-843A was assessed using a combined genomics and metabolomics approach. Whole genome sequencing and molecular networking showed the high biosynthetic potential of this actinomycete. A significant proportion of the genome is dedicated to secondary metabolite production, with biosynthetic gene clusters for nonribosomal peptides, polyketides, and terpenes being the most represented. Seven cyclic pentapeptides, including a putative new analogue, and a glycosylated lanthipeptide were identified using HRMS and untargeted MS/MS analysis. To validate our genome and metabolome analysis, we undertook a mass spectrometry-guided purification and confirmed the production of the known peptides BE-18257A (1) and BE-18257B (2). The production of 1 and 2 and the growth of the microorganism were monitored for eight days. Compound 2 was produced at a higher concentration, starting at 48 h post-incubation. Both compounds were noncytotoxic against colorectal and breast cancer cell lines.
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    Genome mining of a novel marine sponge symbiont Nocardia sp. BML-15-R-026U reveals high biosynthetic potential for secondary metabolites, including a non-ribosomal peptide and a polyketide of high novelty
    Gloria, Paul Christian; Romines, Elaine; Punzalan, Marc Jeremie; Florece, Christine Marie; Cadorna, Kreighton; Salvador-Reyes, Lilibeth; Lluisma, Arturo (Philippine-American Academy of Science and Engineering, 2023-11-28)
    Antibiotic and drug resistance poses serious global public health threats, leading to substantial infections and fatalities annually. Addressing these issues requires the discovery of novel bioactive compounds and a faster and more cost-effective discovery process. However, traditional approaches, which require isolation and multi-step purification of compounds from organisms and running of initial assays, suffer from serious limitations such as the need for substantial amounts of biological material and high rates of compound rediscoveries. Because the biosynthetic capabilities of organisms are encoded in their genomes, genome mining provides a promising solution that would complement traditional approaches. This study conducted long-read whole genome sequencing on a marine sponge symbiont, Nocardia sp. BML-15-R-026U, to explore its genomic repertoire of secondary metabolite-encoding Biosynthetic Gene Clusters (BGCs). A four-contig genome assembly was generated for this isolate with a high degree of completeness and an estimated genome size of 4.84 Mbp. Its genome displays remarkable biosynthetic potential by containing at least 34 distinct secondary metabolite BGCs, predominantly Non-Ribosomal Peptide Synthetase (NRPS) and Polyketide Synthase (PKS) systems capable of producing novel chemical structures. Further analysis was focused on two genomic regions. In region 3.10, the study predicted a BGC for a novel, serine-rich non-ribosomal peptide with a predicted molecular weight of 2754 g/mol. Region 3.12 contained an iterative type-I PKS BGC, suggesting the potential synthesis of a polyketide compound with oxidoreductase-inhibiting properties. This study highlights genome mining as a productive early-phase approach for identifying promising drug leads and has identified the most promising candidates among this isolate’s BGCs for experimental validation.