Biosynthesis of the Peptide Antibiotic Feglymycin by a Linear Nonribosomal Peptide Synthetase Mechanism
Biosynthesis of the Peptide Antibiotic Feglymycin by a Linear Nonribosomal Peptide Synthetase Mechanism
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DOI：
10.1002/cbic.201500432
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发表时间：
2015-12-14
期刊：
影响因子：
3.2
通讯作者：
Suessmuth, Roderich D.
中科院分区：
文献类型：
--
作者：
Gonsior, Melanie;Muhlenweg, Agnes;Suessmuth, Roderich D.
Feglymycin是一种由链霉菌DSM 11171产生的肽类抗生素，主要由非蛋白质苯甘氨酸型氨基酸组成。它对耐甲氧西林金黄色葡萄球菌菌株具有抗菌活性，对HIV具有抗病毒活性。抑制细菌肽聚糖合成的早期步骤表明与其他肽类抗生素不同的作用模式。在这里，我们描述的feglymycin（feg）的生物合成基因簇，编码的13模块非核糖体肽合成酶（NRPS）系统的识别和分配。NRPS基因的失活和用氨基酸L-Hpg补充羟基扁桃酸氧化酶突变体证明了feg簇的身份。Hp相关的非天然氨基酸的喂养不成功。对feg簇的表征是理解这种有效抗菌肽生物合成的重要一步。
Feglymycin, a peptide antibiotic produced by Streptomyces sp. DSM11171, consists mostly of nonproteinogenic phenylglycine-type amino acids. It possesses antibacterial activity against methicillin-resistant Staphylococcus aureus strains and antiviral activity against HIV. Inhibition of the early steps of bacterial peptidoglycan synthesis indicated a mode of action different from those of other peptide antibiotics. Here we describe the identification and assignment of the feglymycin (feg) biosynthesis gene cluster, which codes for a 13-module nonribosomal peptide synthetase (NRPS) system. Inactivation of an NRPS gene and supplementation of a hydroxymandelate oxidase mutant with the amino acid L-Hpg proved the identity of the feg cluster. Feeding of Hpg-related unnatural amino acids was not successful. This characterization of the feg cluster is an important step to understanding the biosynthesis of this potent antibacterial peptide.