硫肽是核糖体生物合成和翻译后修饰的肽 (RiPP)，可通过靶向蛋白质生物合成的多个步骤来有效抑制革兰氏阳性菌的生长。硫肽的药理学特性较差，特别是其水溶性低，阻碍了它们发展成临床有用的抗生素。对放线菌提取物文库的抗菌活性筛选发现了来自放线菌属的新型多糖基化硫肽 persiathiacins A 和 B。 UTMC 2448。Persiathiacin A 对耐甲氧西林金黄色葡萄球菌和几种结核分枝杆菌菌株（包括耐药和多重耐药临床分离株）具有活性，并且在浓度高达 400 μM 时不会显着影响卵巢癌细胞的生长。多糖基化硫肽极其罕见，并且对其生物合成一无所知。 Actinokineospora sp. 的测序和分析。 UTMC 2448 基因组能够识别假定的 persiathiacin 生物合成基因簇 (BGC)。该基因簇编码的细胞色素 P450 在体外和体内催化那西肽的羟基化，这与该基因簇指导 persiathiacin 生物合成的提议一致。该簇中的几个基因编码已知在其他类别的糖基化天然产物的生物合成过程中催化脱氧糖的组装和附着的酶的同源物。其中一种编码糖基转移酶，该酶在体外催化 D-葡萄糖残基与那西肽的附着。因此，persiathiacins 及其 BGC 的发现为生物合成工程方法的开发提供了基础，以创建具有增强药理学特性的新型（多）糖基化硫肽衍生物。

Thiopeptides are ribosomally biosynthesized and post-translationally modified peptides (RiPPs) that potently inhibit the growth of Gram-positive bacteria by targeting multiple steps in protein biosynthesis. The poor pharmacological properties of thiopeptides, particularly their low aqueous solubility, has hindered their development into clinically useful antibiotics. Antimicrobial activity screens of a library of Actinomycetota extracts led to discovery of the novel polyglycosylated thiopeptides persiathiacins A and B from Actinokineospora sp. UTMC 2448. Persiathiacin A is active against methicillin-resistant Staphylococcus aureus and several Mycobacterium tuberculosis strains, including drug-resistant and multidrug-resistant clinical isolates, and does not significantly affect the growth of ovarian cancer cells at concentrations up to 400 μM. Polyglycosylated thiopeptides are extremely rare and nothing is known about their biosynthesis. Sequencing and analysis of the Actinokineospora sp. UTMC 2448 genome enabled identification of the putative persiathiacin biosynthetic gene cluster (BGC). A cytochrome P450 encoded by this gene cluster catalyzes the hydroxylation of nosiheptide in vitro and in vivo, consistent with the proposal that the cluster directs persiathiacin biosynthesis. Several genes in the cluster encode homologues of enzymes known to catalyze the assembly and attachment of deoxysugars during the biosynthesis of other classes of glycosylated natural products. One of these encodes a glycosyl transferase that was shown to catalyze attachment of a D-glucose residue to nosiheptide in vitro. The discovery of the persiathiacins and their BGC thus provides the basis for the development of biosynthetic engineering approaches to the creation of novel (poly)glycosylated thiopeptide derivatives with enhanced pharmacological properties.