Metabolic Engineering 2012-07-01

Engineering of an industrial polyoxin producer for the rational production of hybrid peptidyl nucleoside antibiotics.

Lipeng Zhai, Shuangjun Lin, Dongjing Qu, Xuechuan Hong, Linquan Bai, Wenqing Chen, Zixin Deng

文献索引：Metab. Eng. 14(4) , 388-93, (2012)

全文：HTML全文

摘要

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.Copyright © 2012 Elsevier Inc. All rights reserved.