Heterologous expression of a polyketide synthase ACRTS2 in Aspergillus oryzaeproduces host-selective ACR toxins: coproduction of minor metabolites

Previously, we succeeded to produce the core structure of the host-selective ACR toxin (1) on brown leaf spot on rough lemon when the polyketide synthase ACRTS2gene was heterologously expressed in Aspergillus oryzae(AO). To confirm the production of 1in AO, the detection limit and suppressing decarboxylation were improved, and these efforts led us to conclude the direct production of 1instead of its decarboxylation product. During this examination, minor ACR-toxin-related metabolites were found. Their structure determination enabled us to propose a decarboxylation mechanism and a novel branching route forming byproducts from the coupling of the dihydropyrone moiety of 1with the acetaldehyde and kojic acid abundant in AO. The involvement of putative cyclase ACRTS3 in the chain release of linear polyketide was excluded by the coexpression analysis of ACRTS2and ACRTS3. Taken together, we concluded that the production of 1in AO is solely responsible for ACRTS2.Graphical AbstractHeterologous expression of a polyketide synthase ACRTS2 produces host-selective ACR toxin and its adducts with endogenous metabolites.