  Sponges have long been recognized as a rich source of bioactive natural
products. Various studies suggest that many of these compounds are produced by
symbiotic bacteria. However, substance supplies and functional insights about
the producers remain limited because cultivation remains unsuccessful. To
identify alternative, sustainable sources of sponge-derived polyketides, we
computationally analyzed 5289 characterized and orphan trans-acyltransferase
polyketide synthases, enzymes with widespread roles in polyketide biosynthesis
by bacterial symbionts. The analytical workflow predicted marine animal-derived
Acidobacteria of the family Acanthopleuribacteraceae with large sets of
biosynthetic gene clusters to be enriched in sponge-type chemistry. Targeted
compound isolation from a chiton-associated strain yielded new congeners of the
phorboxazoles and calyculins, potent and scarce cytotoxins exclusively known
from sponges. These first natural products of Acidobacteria and new coral
metagenomic data on a third family member suggest animal-associated
Acanthopleuribacteraceae as a rich source of sponge-type as well as novel
metabolites
