Characterization of an Orphan Type III Polyketide Synthase Conserved in Uncultivated “Entotheonella” Sponge Symbionts

Abstract

Uncultivated bacterial symbionts from the candidate genus “Entotheonella” have been shown to produce diverse natural products previously attributed to their sponge hosts. In addition to these known compounds, “Entotheonella” genomes contain rich sets of biosynthetic gene clusters that lack identified natural products. Among these is a small type III polyketide synthase (PKS) cluster, one of only three clusters present in all known “Entotheonella” genomes. This conserved “Entotheonella” PKS ( cep) cluster encodes the type III PKS CepA and the putative methyltransferase CepB. Herein, the characterization of CepA as an enzyme involved in phenolic lipid biosynthesis is reported. In vitro analysis showed a specificity for alkyl starter substrates and the production of tri‐ and tetraketide pyrones and tetraketide resorcinols. The conserved distribution of the cep cluster suggests an important role for the phenolic lipid polyketides produced in “Entotheonella” variants.

Abstract

Common ground: Few of the diverse biosynthetic gene clusters found in uncultivated “Entotheonella” sponge symbionts are shared between phylotypes, and all of these are functionally uncharacterized. Herein, the characterization of conserved type III polyketide synthase (PKS) CepA is reported and it is shown that it produces phenolic lipids.