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Decoding And Reprogramming Fungal Iterative Nonribosomal Peptide Synthetases, Daya Yu, Fuchao Xu, Shuwei Zhang, Jixun Zhan

Biological Engineering Faculty Publications

Nonribosomal peptide synthetases (NRPSs) assemble a large group of structurally and functionally diverse natural products. While the iterative catalytic mechanism of bacterial NRPSs is known, it remains unclear how fungal NRPSs create products of desired length. Here we show that fungal iterative NRPSs adopt an alternate incorporation strategy. Beauvericin and bassianolide synthetases have the same C₁-A₁-T₁-C₂-A₂-MT-T_2a-T_2b-C₃ domain organization. During catalysis, C₃ and C₂ take turns to incorporate the two biosynthetic precursors into the growing depsipeptide chain that swings between T₁ and T …