Novel Synthetic Biology for the Generation of 'Unnatural' Peptides

目前被用作抗癌和抗生素的许多生物活性天然产物是在微生物中由称为非核糖体多肽合成酶(NRPS)的多功能酶生物合成的。这些自然产生的‘肽工厂’被视为开发新的合成生物学以产生‘非天然’肽的良好起点：这些分子仍然是通过生物合成产生的，但在结构上与原始的肽产品不同，并且可能具有同等或更高的价值。该博士项目的目的是开发一种在体内产生非天然肽的新的化学酶方法：通过利用化学构建块和工程NRPS酶/途径，希望产生一个具有制药和工业价值的新型多肽化合物的库。

Many bioactive natural products currently utilised as anticancer and antibiotic agents are biosynthesized in microorganisms by multifunctional enzymes known as nonribosomal peptide synthetases (NRPSs). These naturally occurring 'peptide factories' are seen as the promising starting point for the development of novel synthetic biology towards the generation of 'unnatural' peptides: these are molecules still produced via biosynthesis but are structurally different from the original peptide products, and may be of equal or superior value.The aim of this PhD project is to develop a novel chemoenzymatic approach towards the in vivo generation of unnatural peptides: by utilising chemical building blocks and engineered NRPS enzymes/pathways it is hoped to generate a library of novel peptide compounds of pharmaceutical and industrial interest.