The leader peptide is not required for post-translational modification by lacticin 481 synthetase
The leader peptide is not required for post-translational modification by lacticin 481 synthetase
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DOI：
10.1021/ja072967
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发表时间：
2007-08-29
影响因子：
15
通讯作者：
van der Donk, Wilfred A.
中科院分区：
文献类型：
--
作者：
Levengood, Matthew R.;Patton, Gregory C.;van der Donk, Wilfred A.
羊毛硫抗生素是一种后修饰的抗菌肽。修饰过程的特征在于将Ser和Thr残基脱水为相应的脱氢丙氨酸（Dha）和脱氢丁酸（Dhb）残基，以及随后通过半胱氨酸硫醇缀合加成到C10氨基酸上。核糖体合成的肽前体含有在成熟过程中不被修饰的N-末端前导肽和被转化为lantibiotic的C-末端结构区。前导肽的作用一直是许多推测的主题。将乳酸菌素481合成酶与结构肽（前导肽以反式提供）一起孵育导致四个脱水中的三个脱水，表明前导肽和结构区之间不需要共价连接。在没有前导肽的情况下，乳酸菌素481合成酶与结构肽一起孵育仍然导致脱水，尽管活性降低。这些发现表明，前导肽并不是脱水所绝对需要的。
Lantibiotics are post-translationally modified antimicrobial peptides. The modification process features dehydration of Ser and Thr residues to the corresponding dehydroalanine (Dha) and dehydrobutyrine (Dhb) residues and the subsequent conjugate addition by cysteine thiols onto the dehydro amino acids. The ribosomally synthesized peptide precursors contain an N-terminal leader peptide that is not modified during maturation and a C-terminal structural region that is transformed into the lantibiotic. The role of the leader peptide has been the subject of much speculation. Incubation of lacticin 481 synthetase with the structural peptide (with the leader peptide provided in trans) resulted in three of four dehydrations showing that a covalent link between the leader peptide and the structural region is not required. Incubation of lacticin 481 synthetase with the structural peptide in the absence of the leader peptide still resulted in dehydration, although the activity was reduced. These findings show that the leader peptide is not absolutely required for dehydration.