CytA, a reductase in the cytorhodin biosynthesis pathway, inactivates anthracycline drugs in Streptomyces.

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2019
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Abstract
Antibiotic-producing microorganism can develop strategies to deal with self-toxicity. Cytorhodins X and Y, cosmomycins A and B, and iremycin, are produced as final products from a marine-derived Streptomyces sp. SCSIO 1666. These C-7 reduced metabolites show reduced antimicrobial and comparable cytotoxic activities relative to their C-7 glycosylated counterparts. However, the biosynthetic mechanisms and relevant enzymes that drive C-7 reduction in cytorhodin biosynthesis have not yet been characterized. Here we report the discovery and characterization of a reductase, CytA, that mediates C-7 reduction of this anthracycline scaffold; CytA endows the producer Streptomyces sp. SCSIO 1666 with a means of protecting itself from the effects of its anthracycline products. Additionally, we identified cosmomycins C and D as two intermediates involved in cytorhodin biosynthesis and we also broadened the substrate specificity of CytA to clinically used anthracycline drugs.
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gui2019cytacommunications Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Gui, Chun;Chen, Jiang;Xie, Qing;Mo, Xuhua;Zhang, Shanwen;Zhang, Hua;Ma, Junying;Li, Qinglian;Gu, Yu-Cheng;Ju, Jianhua;
Journal Communications biology
Year 2019
DOI
10.1038/s42003-019-0699-5
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Keywords
Atrial fibrillation blood pressure accuracy oscillometric sinus rhythm

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