Mining Chromodoris quadricolor symbionts for biosynthesis of novel secondary metabolites

Many secondary metabolites with medicinal potential are produced by various animals, plants, and microorganisms. Because marine creatures have a greater proportion of unexplored biodiversity than their terrestrial counterparts, they have emerged as a key research focus for the discovery of natural product drugs. Several studies have revealed that bacteria isolated from Chromodoris quadricolor (C. quadricolor) have antibiotic and anticancer properties. In this study, meta-transcriptomics and meta-proteimic analysis were combined to identify biosynthetic gene clusters (BGCs) in the symbiotic bacteria of the C. quadricolor mantle. Symbiotic bacteria were separated from the host by differential pelleting, and then total RNA was extracted, purified, and sequenced. Meta-transcriptomic analysis was done using different natural product mining tools to identify biosynthetic transcript clusters (BTCs). Furthermore, proteins were extracted from the same cells and then analyzed by LC-MS. A meta-proteomic analysis was performed to find proteins that are translated from BCGs. Finally, only 227 proteins have been translated from 40,742 BTCs. The majority of these clusters were polyketide synthases (PKSs) with antibacterial activity. Ten novel potential metabolic clusters with the ability to produce antibiotics have been identified in Novosphingobium and Microbacteriaceae, including members of the ribosomal synthesized and post-translationally modified peptides (RiPPs), polyketide synthases, and others. We realized that using a meta-proteomic approach to identify BGCs that have already been translated makes it easier to concentrate on BGCs that are utilized by bacteria. The symbiotic bacteria associated with C. quadricolor could be a source of novel antibiotics.