A new enzyme involved in the control of the stereochemistry in the decalin formation during equisetin biosynthesis

Tetramic acid containing a decalin ring such as equisetin and phomasetin is one of the characteristic scaffolds found in fungal bioactive secondary metabolites. Polyketide (PKS)-nonribosomal peptide synthetase (NRPS) hybrid enzyme is responsible for the synthesis of the polyketide scaffold conjugated with an amino acid. PKS-NRPS hybrid complex programs to create structural diversity in the polyketide backbone have begun to be investigated, yet mechanism of control of the stereochemistry in a decalin formation via a Diels-Alder cycloaddition remains uncertain. Here, we demonstrate that fsa2, which showed no homology to genes encoding proteins of known function, in the fsa cluster responsible for equisetin and fusarisetin A biosynthesis in Fusarium sp. FN080326, is involved in the control of stereochemistry in decalin formation via a Diels-Alder reaction in the equisetin biosynthetic pathway. •Fusarisetin A biosynthetic gene cluster was identified in Fusarium sp. FN080326.•Equisetin is a biosynthetic intermediate of fusarisetin A.•(3S,6R)-diastereomer of equisetin was isolated from the fsa2 deletion mutant.•Fsa2 is involved in the stereoselective decalin formation of equisetin.