Alanine Scan of the Peptide Antibiotic Feglymycin: Assessment of Amino Acid Side Chains Contributing to Antimicrobial Activity
Alanine Scan of the Peptide Antibiotic Feglymycin: Assessment of Amino Acid Side Chains Contributing to Antimicrobial Activity
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DOI：
10.1002/cbic.201300032
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发表时间：
2013-03-18
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：
Haenchen, Anne;Rausch, Saskia;Suessmuth, Roderich D.
抗生素非淋霉素是由链霉菌合成的一种线状13聚体多肽。帝斯曼11171。它主要由非蛋白性氨基酸4-羟基苯甘氨酸和3，5-二羟基苯甘氨酸组成。非淋霉素的丙氨酸扫描是通过溶液相肽合成进行的，以评估单个氨基酸侧链对生物活性的重要性。因此，从双肽和三肽构建块合成了13个肽，并随后测试了其对金黄色葡萄球菌的抗菌活性。此外，我们还测试了被非淋霉素抑制的肽聚糖生物合成酶Mura和MurC的抑制作用。抗菌活性主要基于D-Hpg1、L-Hpg5和L-Phe12三个氨基酸，而对Mura和MurC的抑制活性主要依赖于L-Asp13。抗菌活性和酶抑制的位置依赖关系的差异表明，非淋霉素的作用方式具有多个分子靶点。
The antibiotic feglymycin is a linear 13-mer peptide synthesized by the bacterium Streptomyces sp. DSM 11171. It mainly consists of the nonproteinogenic amino acids 4-hydroxyphenylglycine and 3,5-dihydroxyphenylglycine. An alanine scan of feglymycin was performed by solution-phase peptide synthesis in order to assess the significance of individual amino acid side chains for biological activity. Hence, 13 peptides were synthesized from di- and tripeptide building blocks, and subsequently tested for antibacterial activity against Staphylococcus aureus strains. Furthermore we tested the inhibition of peptidoglycan biosynthesis enzymes MurA and MurC, which are inhibited by feglymycin. Whereas the antibacterial activity is significantly based on the three amino acids D-Hpg1, L-Hpg5, and L-Phe12, the inhibitory activity against MurA and MurC depends mainly on L-Asp13. The difference in the position dependence for antibacterial activity and enzyme inhibition suggests multiple molecular targets in the modes of action of feglymycin.