A Type III Polyketide Synthase Specific for Sporulating Negativicutes is Responsible for Alkylpyrone Biosynthesis

Genomic analyses indicate that anaerobic bacteria represent a neglected source of natural products. Whereas a limited number of polyketides have been reported from anaerobes, products of type III polyketide synthases (PKSs) have remained unknown. We found a highly conserved biosynthetic gene cluster (BGC) comprising genes putatively encoding a type III PKS and a methyltransferase in genomes of the Negativicutes, strictly anaerobic, diderm bacteria. By in vivo and in vitro expression of a type III PKS gene, dquA from the oak‐associated Dendrosporobacter quercicolus in E. coli we show production of long‐chain alkylpyrones. Intriguingly, this BGC is specific for sporulating Sporomusaceae but absent in related Negativicutes that do not sporulate, thus suggesting a physiological role.