Maturation and secretion of nisin A from Lactococcus lactis

乳酸乳球菌的成熟和乳链菌肽 A 的分泌

• 批准号: 233110675
• 负责人: Professor Dr. Lutz Schmitt
• 金额: --
• 依托单位: Lehrstuhl für Biochemie I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/233110675?language=en
• 关键词: Maturation; secretion; nisin; Lactococcus; lactis

Nisin A (NisA) is the best-known lantibiotic, a peptide antibiotic that is characterized by the presence of thioether rings called (methyl)lantionine depending on the non-natural amino acids that forms the ring. In the case of NisA five rings are present. NisA is ribosomally synthesized as a precursor containing a leader sequence of 23 amino acids and active NisA, composed of 34 amino acids that possess antimicrobial activity against Gram-positive bacteria. The operon responsible for NisA synthesis consists of 11 genes, four of which are involved in the maturation and secretion. The maturation steps involve dehydration of serine and threonine residues to form dehydroalanine (Ser) and dehydrobutyrine (Thr), respectively. This step is catalyzed by the dehydratase NisB. Subsequently, the cyclase NisC catalyzes the cyclization step resulting in fully modified NisA and ring formation. Finally, fully modified NisA is secreted by the ABC transporter NisT and converted into its biological active form (NisA) by the action of the serine protease NisP, which removes the leader sequence in the extracellular medium. Here, we like to gather biochemical, biophysical and structural knowledge to understand the complex interplay of four enzymes that result in the formation of a biological active lantibiotic.

Nisin A(NISA)是最广为人知的一种抗生素，是一种多肽抗生素，其特征是存在称为(甲基)蓝硫氨酸的硫醚环，这取决于形成环的非天然氨基酸。在NISA的例子中，有五个环。NISA是核糖体合成的前体，含有23个氨基酸的前导序列和由34个氨基酸组成的活性NISA，对革兰氏阳性菌具有抗菌活性。负责NISA合成的操纵子由11个基因组成，其中4个基因参与成熟和分泌。成熟步骤包括丝氨酸和苏氨酸残基脱水，分别生成脱氢丙氨酸(Ser)和脱氢丁碱(Thr)。这个步骤是由脱水酶NisB催化的。随后，环化酶NISC催化环化步骤，导致完全修饰的NISA和环的形成。最后，ABC转运蛋白NIST分泌完全修饰的NISA，并在丝氨酸蛋白酶NISP的作用下转化为其生物活性形式(NISA)，从而去除细胞外培养上清液中的前导序列。在这里，我们希望收集生化、生物物理和结构方面的知识，以了解导致生物活性抗生素形成的四种酶的复杂相互作用。