Nazari Behnam, Forneris Clarissa C, Gibson Marcus I, Moon Kyuho, Schramma Kelsey R, Seyedsayamdost Mohammad R
Department of Chemistry , Princeton University , Princeton , NJ 08544 , USA . Email:
Department of Molecular Biology , Princeton University , Princeton , NJ 08544 , USA.
Medchemcomm. 2017 Apr 1;8(4):780-788. doi: 10.1039/c6md00637j. Epub 2017 Jan 30.
Glycopeptide antibiotics (GPAs) have served as potent clinical drugs and as an inspiration to chemists in various disciplines. Among known GPAs, complestatin, chloropeptin, and kistamicin are unique in that they contain an unusual indole-phenol crosslink. The mechanism of formation of this linkage is unknown, and to date, the biosynthetic gene cluster of only one GPA with an indole-phenol crosslink, that of complestatin, has been identified. Here, we report the genome sequence of the kistamicin producer sp. ATCC 55076. We find that this strain harbours the largest actinobacterial chromosome to date, consisting of a single linear chromosome of ∼13.1 Mbp. AntiSMASH analysis shows that ∼32 biosynthetic gene clusters and ∼10% of the genome are devoted to production of secondary metabolites, which include 1,6-dihydroxyphenazine and nomuricin, a new anthraquinone-type pentacyclic compound that we report herein. The kistamicin gene cluster () was identified bioinformatically. A unique feature of is that it contains two cytochrome P450 enzymes, which likely catalyze three crosslinking reactions. These findings set the stage for examining the biosynthesis of kistamicin and its unusual indole-phenol crosslink in the future.
糖肽类抗生素（GPAs）一直是强效临床药物，并启发了各个学科的化学家。在已知的GPAs中，制癌菌素、氯肽菌素和杀稻瘟菌素很独特，因为它们含有一种不寻常的吲哚 - 酚交联。这种连接的形成机制尚不清楚，迄今为止，仅鉴定出一种具有吲哚 - 酚交联的GPA（制癌菌素）的生物合成基因簇。在此，我们报道了杀稻瘟菌素产生菌sp. ATCC 55076的基因组序列。我们发现该菌株拥有迄今为止最大的放线菌染色体，由一条约13.1 Mbp的线性染色体组成。抗SMASH分析表明，约32个生物合成基因簇和约10%的基因组用于次级代谢产物的产生，其中包括1,6 - 二羟基吩嗪和诺马菌素（我们在此报道的一种新的蒽醌型五环化合物）。通过生物信息学方法鉴定出了杀稻瘟菌素基因簇（）。的一个独特特征是它含有两种细胞色素P450酶，这可能催化三个交联反应。这些发现为未来研究杀稻瘟菌素的生物合成及其不寻常的吲哚 - 酚交联奠定了基础。
