Depside Bond Formation by the Starter-Unit Acyltransferase Domain of a Fungal Polyketide Synthase.

ABSTRACT

Depsides are polyphenolic molecules comprising two or more phenolic acid derivatives linked by an ester bond, which is called a depside bond in these molecules. Despite more than a century of intensive research on depsides, the biosynthetic mechanism of depside bond formation remains unclear. In this study, we discovered a polyketide synthase, DrcA, from the fungus Aspergillus duricaulis CBS 481.65 and found that DrcA synthesizes CJ-20,557 (1), a heterodimeric depside composed of 3-methylorsellinic acid and 3,5-dimethylorsellinic acid. Moreover, we determined that depside bond formation is catalyzed by the starter-unit acyltransferase (SAT) domain of DrcA. Remarkably, this is a previously undescribed form of SAT domain chemistry. Further investigation revealed that 1 is transformed into duricamidepside (2), a depside-amino acid conjugate, by the single-module nonribosomal peptide synthetase DrcB.