Precursor-directed combinatorial biosynthesis of cephalosporin analogue by endolithic actinobacterium Streptomyces sp. AL51 by utilizing thiophene derivative

利用噻吩衍生物,内生放线菌链霉菌AL51进行前体导向的组合生物合成头孢菌素类似物。

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Abstract

Natural products or their derivatives provide a reliable resource for new drugs. The multi-step chemical reaction to produce new drug is not only expensive but also release pollutants. The precursor-based combinatorial biosynthesis (PCB) is, however, a better option to produce novel natural products with potential pharmaceutical applications. The present work is an attempt to synthesize an antibacterial compound by transforming thiophene precursor using endolithic Streptomyces sp. AL51. The Streptomyces sp. AL51 was isolated from a granite rock sample collected from Mylliem, Meghalaya, India. The isolate was identified as Streptomyces sp. based on its cultural, morphological, biochemical and molecular characteristics. The bioactive compound CAx1 was extracted from the fermentation broth. The compound was characterized by bioactivity-guided fractionation and identified by infrared, UV-visible, nuclear magnetic resonance and mass spectrometry data and identified as 7-[1-(thiophene-5-yl)-1-formamido]-3-propylenyl-3-cephem-4-carboxylic acid with molecular formula C(15)H(14)N(2)O(4)S(2). The purified compound showed considerable in vitro antibacterial activity against both Gram-positive and Gram-negative bacteria showing its broad spectrum property. The obtained results provide promising baseline information for the potential use of endolithic actinobacterium for semisynthetic drug discovery. This is the first report on PCB of broad range antibacterial compound by endolithic Streptomyces strain.

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