鉴定安普瑞霉素基因簇有助于了解 C9 糖核苷抗生素的生物合成。
Identification of the Amipurimycin Gene Cluster Yields Insight into the Biosynthesis of C9 Sugar Nucleoside Antibiotics.
机构信息
Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education , Shenyang Pharmaceutical University , Shenyang 110016 , China.
State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry , University of Chinese Academy of Sciences (CAS), CAS, Shanghai 200032 , China.
出版信息
Org Lett. 2019 May 3;21(9):3148-3152. doi: 10.1021/acs.orglett.9b00840. Epub 2019 Apr 16.
Feeding studies indicate a possible synthetic pattern for the N-terminal cis-aminocyclopentane carboxylic acid (ACPC) and suggest an unusual source of the high-carbon sugar skeleton of amipurimycin (APM). The biosynthetic gene cluster of APM was identified and confirmed by in vivo experiments. A C9 core intermediate was discovered from null mutants of ACPC pathway, and an ATP-grasp enzyme (ApmA8) was reconstituted in vitro for ACPC loading. Our observations allow a first proposal of the APM biosynthetic pathway.
喂养研究表明 N-端顺式-氨基环戊烷羧酸（ACPC）可能具有合成模式，并提示安普霉素（APM）的高碳糖骨架具有不寻常的来源。通过体内实验鉴定并证实了 APM 的生物合成基因簇。从 ACPC 途径的缺失突变体中发现了 C9 核心中间产物，并在体外重建了用于 ACPC 加载的 ATP 抓取酶（ApmA8）。我们的观察结果为 APM 的生物合成途径提供了第一个建议。
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