A bio-enabled synthesis for the glycopeptide antibiotics

本项目旨在通过生物合成细胞色素P450酶催化的肽合成和交联相结合，开发一种体外仿生合成糖肽抗生素（GPAs）的方法。GPA生物合成中的交联步骤对于抗生素活性是必不可少的，但阻碍了它们的化学合成。该项目将研究生物合成P450酶的体外行为和特性。这将提供直接的好处：新的糖肽抗生素衍生物的开发和复杂的化学合成新的生物催化剂的鉴定。所获得的知识也将直接使未来的重组糖肽抗生素生产在体内。

This project aims to develop an in vitro biomimetic synthesis for glycopeptide antibiotics (GPAs) by combining peptide synthesis and crosslinking catalysed by biosynthetic Cytochrome P450 enzymes. The crosslinking step in GPA biosynthesis is essential for antibiotic activity but impedes their chemical synthesis. This project will study the in vitro behaviour and characteristics of the biosynthetic P450 enzymes. This will provide direct benefits: the development of new glycopeptide antibiotic derivatives and the identification of new biocatalysts for complex chemical synthesis. Knowledge gained will also directly enable future reengineering of glycopeptide antibiotic production in vivo.