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

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 sp. AL51. The sp. AL51 was isolated from a granite rock sample collected from Mylliem, Meghalaya, India. The isolate was identified as 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 CHNOS. 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 strain.

Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors

“…Additionally, 9 had more promising cytotoxic potential (IC 50 21.09 µM) than doxorubicin (IC 50 195.12 µM) against CEM/ADR5000 (human T-cell lymphoblast-like cell line). However, it was weakly active toward CCRF-CEM (human leukemic cell line, IC 50 46.96 µM) in the resazurin reduction cytotoxic assay [30].…”

“…The continuous emergence of MDR pathogens drastically reduced the efficacy of the utilized antibiotics resulting in a growth rate of therapeutic failure [62]. Accordingly, new and effective antimicrobial agents to tackle microbial infections are needed [50].…”

Efficient production of valinomycin by the soil bacterium, Streptomyces sp. ZJUT-IFE-354

“…In this study, a Streptomyces strain antagonistic to S. sclerotiorum was isolated from soil using a bioactivity-guided approach and identified by the morphological and 16S rDNA sequence analysis (Das et al 2019;Bhattacharjee et al 2018). The antifungal metabolites were isolated from the culture broth using a variety of chromatographic procedures, and the structure of active metabolite was subsequently elucidated as valinomycin.…”