Bacterial P450 engineering for production of high value antibacterials

用于生产高价值抗菌药物的细菌 P450 工程

• 批准号: NE/V010328/1
• 负责人: Andrew Munro
• 金额: $ 0.76万
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NE%2FV010328%2F1
• 关键词: Bacterial; P450; engineering; production; value

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.

BBSRC：Sian Thistlethwaite：BB/M011208/1 Many Pharmaceutical药物是由传统的有机路线合成的，但是，通过许多困难的综合步骤，这种方法可能是费力且昂贵的。药物合成正朝着诸如生物合成之类的替代合成途径迈进，以发展可持续，更便宜的商业生产途径。这对于抗菌发现至关重要，因为需要替代方法来应对抗菌抗性危机。 P450 BM3通常是由于其快速催化，生物转化的多种范围以及变异的滥交，从而产生有价值的现有和新型代谢物。我们的目的是通过在Auclair组中开发的抗菌和细菌调节的pantothenamide类似物来解决MUNRO组在Munro组中开发的BM3的变体来解决抗菌抗性的问题。将针对几种细菌菌株筛选新的类似物，以评估其抗菌/细菌调节活性。利用生物合成产生一类化合物的新型类似物，这些化合物可能会使宿主免疫系统对传染性细菌产生敏感性，这可能会产生几种类似物的抗菌作用模式。