Integrative metabolo-genomics suggests a biosynthetic pathway for tetrangulol in Streptomyces sp. KL110A.

Natural products (NPs) of microbial origin are highly valued for their diverse bioactive properties. Among bacteria, Streptomyces stands out as a prolific source of NPs with applications in medicine and agriculture. Recent advances in metabolomics, and bioinformatics as well as the abundance of genomic data have revolutionized the study of NPs, enabling the rapid connection of biosynthetic pathways and metabolites. However, discovering novel compounds from large pools of genomes and strains is cumbersome. Metabolo-genomics approaches are promising strategies that can save time and resources at initial stages of the natural product discovery pipeline by rapidly linking molecules and their biosynthetic genes. Here, we present genomic characterization and metabolomic profiling of Streptomyces sp. KL110A, a strain isolated from the rainforest soils of Calakmul, Campeche in Mexico. Using genome mining tools and LC-MS/MS metabolomics, we identified and characterized known biosynthetic gene clusters (BGCs) and proposed a biosynthetic mechanism for the biosynthesis of the benz(a)anthraquinone tetrangulol. Our findings underscore the relevance of integrating genomic and metabolomic approaches in elucidating novel biosynthetic pathways, positively contributing to the field of natural product research.