title: Engineering of an industrial polyoxin producer for the rational production of hybrid peptidyl nucleoside antibiotics.
abstract: Polyoxins and nikkomycins are potent antifungal peptidyl nucleoside antibiotics, which inhibit fungal cell wall biosynthesis. They consist of a nucleoside core and one or two independent peptidyl moieties attached to the core at different sites. Making mutations and introducing heterologous genes into an industrial Streptomyces aureochromogenes polyoxin producer, resulted in the production of four polyoxin-nikkomycin hybrid antibiotics designated as polyoxin N and nikkoxin B-D, whose structures were confirmed using high resolution MS and NMR. Two of the hybrid antibiotics, polyoxin N and nikkoxin D, were significantly more potent against some human or plant fungal pathogens than their parents. The data provides an example for rational generation of novel peptidyl nucleoside antibiotics in an industrial producer.
authors.affiliation: State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Lipeng
authors.initials: L
authors.lastname: Zhai
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Lin
authors.forename: Dongjing
authors.initials: D
authors.lastname: Qu
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Hong
authors.forename: Linquan
authors.initials: L
authors.lastname: Bai
authors.forename: Wenqing
authors.initials: W
authors.lastname: Chen
authors.forename: Zixin
authors.initials: Z
authors.lastname: Deng
mesh_terms: D000617:Aminoglycosides / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D000935:Antifungal Agents / Q000378:metabolism*; D060847:Metabolic Engineering / Q000379:methods; D009154:Mutation; D011741:Pyrimidine Nucleosides / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D013302:Streptomyces / Q000378:metabolism
chemical_list: D000617:Aminoglycosides; D000935:Antifungal Agents; D011741:Pyrimidine Nucleosides; C002457:polyoxin; C011952:nikkomycin