From nucleotide to gene cluster: Differences driving the specialized metabolism of the marine actinomycete Salinispora

Bacteria are the source of many important medicines, including antibiotics, anticancer, anti-inflammatory, and antiviral. In the last decades, the increased access to bacterial genome sequences revealed a wealth of unexplored biosynthetic potential. This discovery has revolutionized the way we research natural products. One remarkable example of natural product wealth is the marine actinomycete Salinispora, a prolific producer of many specialized metabolites with various biological activities and exceptional structures. However, our understanding of the evolutive and ecological forces driving specialized metabolism in bacteria remains limited. Here I studied the genomic differences driving the specialized metabolism of Salinispora via an omics approach. I started with a comprehensive assessment of biosynthetic gene cluster distributions and metabolite production patterns in Salinispora spp., resulting in 15 unique biosynthetic gene clusters distributed across seven different species. Subsequently, I assessed the expression of these unique biosynthetic gene clusters in standard laboratory conditions for Salinispora, finding 80% of the species-specific biosynthetic genes to be silent. I then, focused on ketomemicin and its biosynthetic gene cluster distribution in Salinispora. I found two new ketomemicin analogs and discovered the ketomemicin gene cluster is highly conserved in Salinispora, but surprisingly scarce in other actinomycetes. Additionally, I investigated the genomic differences behind a rare mutation disrupting the production of the glycosylated carotenoid sioxanthin in six different strains of two Salinispora species. I was able to link the albino phenotype to several point mutations in coding and non-coding regions of genes related to early stages of sioxanthin production. The extend of the ecological outcomes of this mutation remains to be determined. My findings provide insights into the genomic differences governing the specialized metabolism in Salinispora and suggest its importance as a phenotypic difference in their species. Further, it extends our knowledge on the biosynthetic potential Salinispora harbors, arising curiosity on the environmental and ecological dynamics Salinispora has adapted in nature that resulted in the vast natural product repertoire it contains