Liras Paloma
Área de Microbiología, Departamento de Biología Molecular, Facultad de Ciencias Biológicas y Ambientales, Universidad de León, 24071, León, Spain,
Appl Microbiol Biotechnol. 2014 Feb;98(3):1023-30. doi: 10.1007/s00253-013-5410-z. Epub 2013 Dec 10.
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.
全霉素是二硫代吡咯烷酮类次级代谢产物的一员。它含有一个由两个杂环形成的发色团，其中一个带有二硫键。全霉素发色团也存在于硫菌素、金霉素、嗜线虫杆菌素和复杂的硫代海葵醇中。棒状链霉菌ATCC 27064含有全霉素基因簇（hlm）。这种抗生素由一个半胱氨酸激活的非核糖体肽合成酶形成，随后通过一组四种不同的黄素蛋白进行四个还原步骤；中间体由硫醇氧化酶环化并通过酰化修饰。全霉素是一种广谱抗生素，据报道具有抗肿瘤作用，在体内作用于RNA合成。生产菌株在细胞内通过甲基化和形成异二聚体对其进行修饰，作为一种自我保护方式。全霉素可能是生产具有更高活性和更低毒性的新型杂合化合物的先导分子。
