Engineering Fungal Nonribosomal Peptide Synthetases for Novel Alkaloids

该项目旨在利用结构生物学辅助的蛋白质结构域改组来解码和设计真菌中一类称为非核糖体肽合成酶（NRPS）的模块化巨酶。它们负责肽衍生的生物活性分子的生物合成，例如抗生素青霉素和免疫抑制剂环孢菌素。该项目的预期成果包括一个真菌NRPS工程平台，用于产生具有理想生物活性的新分子，这些分子可以很容易地扩大规模用于可持续的生物生产。这将通过发展尖端生物技术以及发现新的药物、兽医产品和农用化学品，为澳大利亚带来重大利益。

This project aims to use protein-domain shuffling aided by structural biology to decode and engineer a class of modular megaenzymes, called nonribosomal peptide synthetases (NRPSs), in fungi. These are responsible for the biosynthesis of peptide-derived bioactive molecules, such as the antibiotic penicillin and the immunosuppressant cyclosporin. Expected outcomes of this project include a fungal NRPS engineering platform for generating new molecules with desirable biological activities that can be readily scaled up for sustainable bioproduction. This will provide significant benefits to Australia through the development of cutting-edge biotechnologies as well as the discovery of new pharmaceuticals, veterinary products and agrichemicals.