Distribution of biosynthetic gene clusters for complestatin and related compounds in Streptomyces spp.

Aim. In current work we have analyzed 2664 genomes of Streptomyces spp. (publically available from GenBank) searching for complestatin-like biosynthetic gene clusters (BGCs). Then we aimed to reconstruct in silico putative biosynthetic pathways, encoded within these BGCs, estimating the chemical variability of complestatin-like compounds from natural sources. Methods. Widely accepted genome-mining tools and approaches for phylogenetic reconstruction were utilized in this work. Results. 53 genomes of Streptomyces spp. were found to contain complestatin-like BGCs, although only 33 BGCs were found within one contig – others were partial or highly fragmented. Reconstruction of multi-locus phylogeny for 33 found BGCs and complestatin BGC allowed to divide all these BGCs into five phylogenetic subgroups. Representatives of each subgroup exhibited characteristic organization of corresponding BGCs. Reconstruction of putative biosynthetic pathways allowed us to predict that discovered BGCs might potentially code the biosynthesis of new complestatin derivatives: norcomplestatin, N-malonyl-norcomplestatin, and N-acetyl-norcomplestatin. Conclusions. Complestatin-like BGCs are widely distributed among Streptomyces spp. and might encode novel complestain derivatives, which merits further experimental investigation.