Synthetic-biology-based discovery of a fungal macrolide from Macrophomina phaseolina.
Org Biomol Chem. 2020 Mar 27;:
Authors: Morishita Y, Sonohara T, Taniguchi T, Adachi K, Fujita M, Asai T
A synthetic biology approach based on genome mining and heterologous biosynthesis is a powerful tool for discovering novel natural products from a tremendous gene resource. We carried out fungal genome mining guided by a polyketide synthase gene using a public database and found a putative macrolide biosynthetic gene cluster with a highly reducing polyketide synthase gene and a thioesterase gene in Macrophomina phaseolina. Reconstitution of the cluster in Aspergillus oryzae, a model heterologous host for fungal natural product biosynthesis, produced a new 12-membered macrolide, phaseolide A. The absolute stereochemistry was elucidated by vibrational circular dichroism spectroscopy and the crystalline sponge method.
PMID: 32219266 [PubMed – as supplied by publisher]