Genome mining of cryptic tetronate natural products from a PKS-NRPS encoding gene cluster in <i>Trichoderma harzianum</i> t-22
Yiguang Zhu, Junfeng Wang, Pengyun Mou, Yan Yan, Mengbin Chen, Yi Tang
Abstract
Trichoderma harzianum is a widely used biocontrol agent in agriculture. Obtaining a full inventory of the small molecules that can be biosynthesized from the encoded biosynthetic gene clusters (BGCs) is therefore useful for understanding associated plant-microbe and microbe-microbe interactions. Here we heterologously reconstituted a polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) encoding gene cluster from T. harzianum t-22 in Aspergillus nidulans A1145. Six new tetronate natural products trihazone A-F (1-6) were isolated and elucidated by HRESIMS and 1D and 2D NMR data. Three of the products contain an exocyclic olefin, which is derived from the oxidative decarboxylation of an α-ketoglutarate-dependent dioxygenase ThnC as shown by biochemical assays.