Velásquez Juan E, Zhang Xingang, van der Donk Wilfred A
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
Chem Biol. 2011 Jul 29;18(7):857-67. doi: 10.1016/j.chembiol.2011.05.007.
Lantibiotics are ribosomally synthesized and posttranslationally modified antimicrobial peptides. The recently discovered lantibiotic epilancin 15X produced by Staphylococcus epidermidis 15X154 contains an unusual N-terminal lactate group. To understand its biosynthesis, the epilancin 15X biosynthetic gene cluster was identified. The N-terminal lactate is produced by dehydration of a serine residue in the first position of the core peptide by ElxB, followed by proteolytic removal of the leader peptide by ElxP and hydrolysis of the resulting new N-terminal dehydroalanine. The pyruvate group thus formed is reduced to lactate by an NADPH-dependent oxidoreductase designated ElxO. The enzymatic activity of ElxB, ElxP, and ElxO were investigated in vitro or in vivo and the importance of the N-terminal modification for peptide stability against bacterial aminopeptidases was assessed.
羊毛硫抗生素是核糖体合成并经翻译后修饰的抗菌肽。最近发现的由表皮葡萄球菌15X154产生的羊毛硫抗生素表皮兰菌素15X含有一个不寻常的N端乳酸基团。为了解其生物合成过程,鉴定了表皮兰菌素15X的生物合成基因簇。N端乳酸是由ElxB将核心肽第一位的丝氨酸残基脱水产生,随后由ElxP蛋白水解去除前导肽,并将产生的新N端脱氢丙氨酸水解。由此形成的丙酮酸基团被一种名为ElxO的NADPH依赖性氧化还原酶还原为乳酸。对ElxB、ElxP和ElxO的酶活性进行了体外或体内研究,并评估了N端修饰对肽抵抗细菌氨肽酶稳定性的重要性。