Identification and heterologous expression of the globomycin biosynthetic gene cluster
作者机构：Fundacion MEDINACentro de Excelencia en Investigaci´on de Medicamentos Innovadores en AndalucíaAvda del Conocimiento 3418016ArmillaGranadaSpain The Novo Nordisk Foundation Center for BiosustainabilityTechnical University of DenmarkKemitorvetbuilding 2202800 Kgs.LyngbyDenmark
出 版 物：《Synthetic and Systems Biotechnology》 (合成和系统生物技术（英文）)
年 卷 期：2023年第8卷第2期
页 面：206-212页
核心收录：
学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学]
基 金：funded by grants of the Novo Nordisk Foundation Denmark(NNF16OC0021746 to O.G. T.W. NNF20CC0035580 to T.W.)
主 题：Globomycin Signal peptidase II Cyclic lipodepsipeptide Genome mining CRISPR-cBEST Heterologous expression
摘 要：Globomycin is a cyclic lipodepsipeptide originally isolated from several Streptomyces species which displays strong and selective antibacterial activity against Gram-negative *** mode of action is based on the competitive inhibition of the lipoprotein signal peptidase II(LspA),which is absent in eukaryotes and considered an attractive target for the development of new *** its interesting biological properties,the gene cluster encoding its biosynthesis has not yet been *** this study we employed a genome-mining approach in the globomycin-producing Streptomyces ***-278952 to identify a candidate gene cluster responsible for its biosynthesis.A null mutant was constructed using CRISPR base editing where production was abolished,strongly suggesting its involvement in the *** putative gene cluster was then cloned and heterologously expressed in Streptomyces albus J1074 and Streptomyces coelicolor M1146,therefore unambigu-ously linking globomycin and its biosynthetic gene *** work paves the way for the biosynthesis of new globomycin derivatives with improved pharmacological properties.
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