Cross-Chemistry Leads to Product Diversity from Atromentin Synthetases in Aspergilli from Section Nigri.

Summary Non-ribosomal peptide synthetase (NRPS)-like enzymes catalyze the non-oxidative homodimerization of aromatic α-keto acids, but the exact reaction mechanism is unknown. The furanone-forming thioesterase domain of the Aspergillus terreus aspulvinone E synthetase MelA displays a predicted quinone-forming motif, whereby its catalytic triad contains an essential cysteine indicating an unusual thioester intermediate. To convert MelA into a quinone-forming atromentin synthetase its thioesterase domain was replaced with that from a Paxillus involutus or A. terreus atromentin synthetase. Phylogenetic proximity of donor and acceptor seems important, as only replacement with the A. terreus thioesterase was functional. Heterologous expression of atromentin synthetases in Aspergillus niger and Aspergillus oryzae revealed host-dependent product formation whereby cross-chemistry directed atromentin biosynthesis in A. niger toward atrofuranic acid. Screening of aspergilli from section Nigri identified an atromentin synthetase in Aspergillus brasiliensis that produced atrofuranic acid in the homologous host. Therefore, cross-chemistry on quinone cores appears common to section Nigri. Graphical Abstract Highlights • The product spectrum of NRPS-like enzymes depends on the expression platform • Cross-chemistry occurs on quinone core structures in aspergilli from section Nigri • Cross-chemistry produces novel metabolites such as atrofuranic acid • Identification of an atromentin synthetase from Aspergillus brasiliensis Geib et al. investigated core structure formation by thioesterase domains of fungal NRPS-like enzymes. Exchange of thioesterase domains alters product formation, but requires close phylogenetic relationship of donor and acceptor. Product formation further depends on expression hosts with furanic acid rather than quinone core formation in aspergilli from section Nigri. [ABSTRACT FROM AUTHOR]