Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
School of Life Sciences and Biopharmaceutical Sciences, Shenyang Pharmaceutical University, Benxi 117004, China.
J Am Chem Soc. 2020 Apr 1;142(13):5996-6000. doi: 10.1021/jacs.0c01778. Epub 2020 Mar 17.
Miharamycins are peptidyl nucleoside antibiotics with a unique branched C9 pyranosyl amino acid core and a rare 2-aminopurine moiety. Inactivation of 19 genes in the biosynthetic gene cluster and identification of several unexpected intermediates suggest an alternative biosynthetic pathway, which is further supported by feeding experiments and characterization of an unusual adenylation domain recognizing a complex nucleoside derivative as the substrate. These results thereby provide an unprecedented biosynthetic route of high-carbon sugar catalyzed by atypical hybrid nonribosomal peptide synthetase-polyketide synthase.
米拉美霉素是一种具有独特支链 C9 吡喃糖基氨基酸核心和罕见 2-氨基嘌呤部分的肽基核苷抗生素。生物合成基因簇中 19 个基因的失活和几种意外中间体的鉴定表明存在替代生物合成途径，这进一步得到了喂养实验和对识别复杂核苷衍生物作为底物的特殊氨酰化结构域的特征分析的支持。这些结果提供了一种由非典型杂合的非核糖体肽合成酶-聚酮合酶催化的高碳糖的前所未有的生物合成途径。
