Biosynthetic engineering of vibroxin, a novel antibiotic with promising activity against Acinetobacter baumannii

Vibroxin 的生物合成工程，一种具有抗鲍曼不动杆菌活性的新型抗生素

• 批准号: 429874315
• 负责人: Dr. Fayrouz El Maddah
• 金额: --
• 依托单位: Department of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/429874315?language=en
• 关键词: Biosynthetic; engineering; vibroxin; novel; antibiotic

Bacterial natural products and derivatives thereof have been regarded as an invaluable source for many of the commercially available antibiotics, e.g. erythromycin, tetracylines and rifampicin. The proposed project directly addresses the global need for new antibiotics to effectively treat microbial infection and overt the looming health crisis threatened by antibiotic resistant bacteria. The recently characterized novel polyketide vibroxin, from Vibrio rhizosphaerae MSSRF3, exhibits promising antimicrobial activity against multidrug-resistant Acinetobacter baumannii, an opportunistic pathogen and one of the most troublesome hospital-derived (nosocomial) infections. Following successful expression of the vibroxin biosynthetic gene cluster in a heterologous host, the generation of vibroxin analogues via biosynthetic engineering approaches is targeted. The creation of such an analogue library will supply the antibiotic discovery pipeline and further contribute to an understanding of structure-activity relationships (SARs).

细菌天然产物及其衍生物已被认为是许多市售抗生素（例如红霉素、四环素和利福平）的宝贵来源。拟议的项目直接解决了全球对新抗生素的需求，以有效治疗微生物感染，并公开了抗生素耐药性细菌威胁的迫在眉睫的健康危机。最近表征的新的聚酮化合物弧菌毒素，从弧菌根管MSSRF 3，表现出有前途的抗多药耐药鲍曼不动杆菌，一种条件致病菌和最麻烦的医院来源的（医院）感染之一的抗菌活性。在异源宿主中成功表达振动素生物合成基因簇之后，靶向通过生物合成工程方法产生振动素类似物。这种类似物库的创建将提供抗生素发现管道，并进一步有助于理解结构-活性关系（SAR）。