Bacterial P450 engineering for production of high value antibacterials

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BBSRC : Sian Thistlethwaite : BB/M011208/1Many pharmaceutical drugs are synthesised by traditional organic routes, however this approach can be laborious and expensive with many difficult synthesis steps. Pharmaceutical synthesis is moving towards alternative synthetic routes such as biosynthesis in order to develop sustainable, cheaper routes of commercial production. This is crucial for antibacterial discovery, as alternative approaches are required to tackle the antibacterial resistance crisis. P450 BM3 is often utilised due to its rapid catalysis, diverse range of biotransformations and variant promiscuity yielding valuable existing and novel metabolites. We aim to address the problem of antibacterial resistance by screening variants of BM3 developed in the Munro group against antibacterial and bacterio-modulating pantothenamide analogs developed in the Auclair group. New analogs will be screened against several bacterial strains to assess their antibacterial/bacterio-modulating activity. Utilising biosynthesis to produce novel analogs of a class of compounds that will potentially resensitize the host immune system to infectious bacteria may yield several analogs of interest with a new mode of antibacterial action.