In:
Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 56, No. 1 ( 2012-01), p. 110-114
Abstract:
Marinactinospora thermotolerans SCSIO 00652, originating from a deep-sea marine sediment of the South China Sea, was discovered to produce antimicrobial nucleoside antibiotic A201A. Whole-genome scanning and annotation strategies enabled us to localize the genes responsible for A201A biosynthesis and to experimentally identify the gene cluster; inactivation of mtdF , an oxidoreductase gene within the suspected gene cluster, abolished A201A production. Bioinformatics analysis revealed that a gene designated mtdA furthest upstream within the A201A biosynthetic gene cluster encodes a GntR family transcriptional regulator. To determine the role of MtdA in regulating A201A production, the mtdA gene was inactivated in frame and the resulting Δ mtdA mutant was fermented alongside the wild-type strain as a control. High-performance liquid chromatography (HPLC) analyses of fermentation extracts revealed that the Δ mtdA mutant produced A201A in a yield ∼25-fold superior to that of the wild-type strain, thereby demonstrating that MtdA is a negative transcriptional regulator governing A201A biosynthesis. By virtue of its high production capacity, the Δ mtdA mutant constitutes an ideal host for the efficient large-scale production of A201A. These results validate M. thermotolerans as an emerging source of antibacterial agents and highlight the efficiency of metabolic engineering for antibiotic titer improvement.
Type of Medium:
Online Resource
ISSN:
0066-4804
,
1098-6596
DOI:
10.1128/AAC.05278-11
Language:
English
Publisher:
American Society for Microbiology
Publication Date:
2012
detail.hit.zdb_id:
1496156-8
SSG:
12
SSG:
15,3
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