Lanthipeptides are a subclass of ribosomally encoded and post-translationally modified peptides (RiPPs) characterized by the presence of the thioether-containing amino acids lanthionine and methyllanthionine. RiPPs are unique in the natural product landscape as they are large and structurally complex but the biosynthetic gene clusters require minimum genomic space. This small footprint as well as their ribosomally encoded nature make them ideal candidates for heterologous expression and derivatization studies. Genomic analysis has indicated that the Salinispora genus is a prolific producer of natural products, and known compounds from Salinispora often have novel chemical structures and potent biological activity. We analyzed 122 publicly available Salinispora arenicola, tropica, and pacifica genomic sequences for putative lanthipeptide gene clusters and divided the resulting 582 clusters into groups based on sequence similarity. Our results indicated that there are 11 unique groups of lanthipeptides produced by Salinispora. To validate our analysis, we are working to express and characterize lanthipeptides produced by one of these groups. We have chosen two clusters from the same group that are highly similar (94% sequence identity) and are predicted to form the same product; however, the sequence of the leader peptide differs between the two. Comparing in vitro activities of dehydratases from each cluster with these two different leader peptides will provide information about the substrate specificity of the dehydratase. To this end, we have expressed and purified both pre-peptides and dehydratases from each cluster for in vitro studies. These studies are the first steps toward synthesizing the mature lanthipeptide and creating a library of non-natural analogs.

Analysis and characterization of lanthipeptide biosynthetic gene clusters in Salinispora

255th National Meeting (2018)

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