Great achievements in fungal natural product biosynthesis have been harvested recently by Professor Yang Xiaolong’s team from the School of Pharmacy, which were published online on December 24 in the international journal Angew. Chem. Int. Ed. themed Didepside Formation by the Nonreducing Polyketide Synthase Preu6 of Preussia isomera Requires Interaction of Starter Acyl Transferase and Thioesterase Domains (2022, doi:10.1002/anie.202214379; impact factor of 16.823). Liu Qingpei is the first author of the article, with Prof. Yang Xiaolong and Prof. István Molnár from National Technical Research Center of Finland the co-corresponding authors, Zhang Dan and Cai Xianhua respectively the second and fourth author, and SCMZU the first signatory.
Fungal polyketides are a group of natural products with a diversity of chemical structure and important clinical applications. In recent years, the efficient discovery of novel structurally active polyketide natural products and their biosynthetic mechanisms have become a hot spot for research in this field. Professor Yang Xiaolong’s team has discovered a number of new structural polyketide natural products from special habitat fungi, which revealed the new mechanism of important active compounds, revealed the biosynthetic pathway and mechanism of a part of polyketide compounds, and constructed a commercial high-yield engineering strain of mosaic acid series derivatives. Related research results have been published in Chem. Sci., Org. Lett., Cell Death Dis., Front. Microbiol., Food Funct., Front. Nutr., J. Nutr. Biochem., Phytochemistry, ACS Omega, Int. J. Mol. Sci., Tetrahedron Lett., J. Nat. Prod., Org. Biomol. Chem. and other prestigious journals.
Based on a series of research, Prof. Yang’s team further identified Preu6, a polyketide synthase related to the synthesis of mossachromic acid dimer erythromelanic acid, which has important biological activity and commercial application, but its ester bond formation mechanism has not been reported. By employing structural domain exchange, amino acid targeted mutagenesis, structural domain splitting and recombination, the team has revealed a novel enzymatic mechanism of fungal polyketide synthase catalyzing the ester bond formation of erythranilic acid, namely, the rare interaction between the initiating acyltransferase structural domain (SAT) involved in chain initiation and the thioesterase structural domain (TE) involved in chain termination and product release catalyzes ester bond formation, which will provide an important scientific basis for the creation of molecular structural diversity and genetic engineering modification of mosaic acid natural products.
Edited by Liu Qiong Reviewed by Pan Wenjun