There is an urgent quest for new antibiotics. During the past 3 decades over 70% of antimicrobials and over 60% of antitumour agents entering clinical trials have been based on natural products, compounds produced by plants and microorganisms. Whilst such compounds provide an excellent starting point for drug discovery, it is often essential to generate analogues with improved physicochemical properties, or to enable further mechanistic studies. Total synthesis of complex natural products can be lengthy and is not always amenable to analogue generation. Series f analogues may be accessed expeditiously through the use of a synergic combination of synthetic biology and organic synthesis. This project will combine synthetic organic chemistry with synthetic biology and multi-enzyme biocatalysis to access analogues of a new antibiotic, highly potent against VRSE and MSRA, in order to gain insight into its molecular mode of action, thereby enabling the design and generation of new and improved series of this antibiotic.