One size fits all: The semi-synthesis of new undecaprenol analogues for the study of multiple undecaprenyl-processing enzymes

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Antibacterial resistance is a major threat to human health and there is a pertinent need for new antimicrobial targets. Bacteria produce several glycopolymers that are vital to their survival, including peptidoglycan, which is a key component of the bacterial cell wall required for structural integrity. The bacterial cell wall is targeted by many clinically used antibiotics, such as penicillin and vancomycin. Glycopolymer biosynthesis involves several key glycolipid intermediates, all of which are linked to the cell membrane by the molecule undecaprenol. The enzymes that process undecaprenol-linked biomolecules are hot antibiotic targets, as they are unique to bacteria. However, detailed studies on these enzymes and the high-throughput screening of possible inhibitors has been limited due to the lack of suitable probes to monitor their activity. An understanding of enzyme mechanism is a vital pre-requisite to the rationale design of inhibitors. This project aims to develop new labelled analogues of undecaprenol, which will be used to study several novel antibiotic targets and provide a method for the high-throughput screening of potential antibiotic candidates.