Abstract
Holomycin is a member of the dithiolopyrrolone class of secondary metabolites. It contains a cromophore formed by two heterocycles, one of them carrying a disulfide bridge. The holomycin chromophore is also present in thioluthin, aureothricin, the xenorhabdins and the complex thiomarinols. Streptomyces clavuligerus ATCC 27064 contains the holomycin gene cluster (hlm). This antibiotic is formed by a cysteine-activating non-ribosomal peptide synthetase followed by four reduction steps by a set of four different flavoproteins; the intermediate is cyclized by a thiol oxidase and modified by acylation. Holomycin is a broad spectrum antibiotic, reported as antitumoral, acting in vivo on RNA synthesis. It is modified intracellularly by the producer strains by methylation and formation of heterodimers as a way of self-protection. Holomycin might be a lead molecule for the production of new hybrid compounds with higher activity and lower toxicity.
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Acknowledgements
This research was supported by grants BIO2012-34723 from the Spanish Ministry of Science and Innovation and LE046-A11-2 from the Junta de Castilla y León. The author acknowledges the help of Prof. Juan F. Martín and R. Álvarez-Álvarez for critical reading of the manuscript.
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Liras, P. Holomycin, a dithiolopyrrolone compound produced by Streptomyces clavuligerus . Appl Microbiol Biotechnol 98, 1023–1030 (2014). https://doi.org/10.1007/s00253-013-5410-z
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DOI: https://doi.org/10.1007/s00253-013-5410-z