Evolutionary investigations of the biosynthetic diversity in the skin microbiome using lsaBGC

Abstract We developed lsa BGC, a bioinformatics suite that introduces several new methods to expand on the available infrastructure for genomic and metagenomic-based comparative and evolutionary investigation of biosynthetic gene clusters (BGCs). Through application of the suite to four genera commonly found in skin microbiomes, we uncover multiple novel findings on the evolution and diversity of their BGCs. We show that the virulence associated carotenoid staphyloxanthin in Staphylococcus aureus is ubiquitous across the Staphylococcus genus but has largely been lost in the skin-commensal species Staphylococcus epidermidis . We further identify thousands of novel single nucleotide variants (SNVs) within BGCs from the Corynebacterium tuberculostearicum sp. complex, which we describe here to be a narrow, multi-species clade that features the most prevalent Corynebacterium in healthy skin microbiomes. Although novel SNVs were approximately ten times as likely to correspond to synonymous changes when located in the top five percentile of conserved sites, lsaBGC identified SNVs which defied this trend and are predicted to underlie amino acid changes within functionally key enzymatic domains. Ultimately, beyond supporting evolutionary investigations, lsa BGC provides important functionalities to aid efforts for the discovery or synthesis of natural products.