Metagenomic exploration of Mycale hentscheli microbiome secondary metabolite biosynthesis.

The natural environment is replete with potent bioactive organic molecules that are produced by the microorganisms that inhabit it. These so-called secondary metabolites provide niche advantages to the producers and have been exploited by mankind for their medicinal and industrial value, especially as antibiotic and antiproliferative agents. One particular environment that has proven to be a rich source of secondary metabolites are certain species of marine sponge, or more specifically, their microbial symbionts. The New Zealand marine sponge Mycale hentscheli is the source of at least three secondary metabolite like molecules, pateamine, peloruside and mycalamide which have spurred much research interest due to their potent bioactivity. However, the exact origin and genetic factors responsible for the production of these molecules remains unknown.

In this study undertake a metagenomic drug discovery campaign employing multiple sequencing strategies to reveal that these compounds are produced by multiple members of the sponge’s symbiont microbiome. This is in contrast to previously studied sponges where the secondary metabolites are produced by a single species of microorganism. By analysing the biosynthetic gene clusters in their wider genomic context we found the production of the secondary metabolites was achieved by canonical and non-canonical biosynthetic mechanisms. This approach also shed light on an additional repertoire of biosynthetic potential within this already secondary metabolite-rich sponge and provided the complete genomes of novel taxa.

In addition to furthering our understanding of secondary metabolite biosynthesis, we anticipate that the elucidation of the genetic factors responsible for producing the secondary metabolites of M. hentscheli will foster research into their sustainable production by contributing to advances in synthetic biology, heterologous expression and culturing technologies.