LANTIBIOTICS - RIBOSOMALLY SYNTHESIZED BIOLOGICALLY-ACTIVE POLYPEPTIDES CONTAINING SULFIDE BRIDGES AND ALPHA-BETA-DIDEHYDROAMINO ACIDS
LANTIBIOTICS - RIBOSOMALLY SYNTHESIZED BIOLOGICALLY-ACTIVE POLYPEPTIDES CONTAINING SULFIDE BRIDGES AND ALPHA-BETA-DIDEHYDROAMINO ACIDS
复制标题
DOI：
10.1002/anie.199110513
复制
发表时间：
1991-09-01
影响因子：
16.6
通讯作者：
JUNG, G
中科院分区：
文献类型：
--
作者：
JUNG, G
L抗生素是含有链内硫键的多环肽抗生素，由羊硫氨酸和β-甲基羊毛硫氨酸的硫醚基团形成。它们还含有α，β不饱和氨基酸，如二脱氢丙氨酸和二脱氢氨基丁酸。对抗生素生物合成步骤和所涉及的酶的了解使类似的高度修饰多肽的基因技术构建成为可能。乳链菌素是一种重要的食品防腐剂，表皮素是一种高度特异的治疗痤疮的药物，它是一系列酶抑制剂，也是一种具有免疫学意义的活性多肽。抗生素是由核糖体合成产生的，从不活跃的前体蛋白(前抗生素)开始。后者通过酶修饰在翻译后转化为活性多肽抗生素。修饰酶影响丝氨酸和苏氨酸残基的脱水以及半胱氨酸硫醇基团在生成的α，β-不饱和双键上的立体专一性加成，从而导致几个硫键的形成。当先导肽随后被蛋白质降解时，就形成了具有生物活性的抗生素。对抗生素及其前肽的构象分析使人们能够获得关于生物合成的机制和步骤的信息。针对合成前肽序列的抗体和用于多肽分析的现代仪器方法允许对生物合成中间体的结构进行阐明。
Lantibiotics are polycyclic peptide antibiotics containing intrachain sulfide bridges, formed from the thioether groups of the amino acids lanthionine and β‐methyllanthionine. They also contain α,β‐unsaturated amino acids such as didehydroalanine and didehydroaminobutyric acid. A knowledge of the lantibiotic biosynthetic steps and the enzymes involved makes possible a gene technological construction of analogous highly modified polypeptides. To the family of lantibiotics belong nisin, an important food preservative, epidermin, a highly specific therapeutic agent against acne, a series of enzyme inhibitors, as well as immunologically interesting active peptides. Lantibiotics are produced by ribosomal synthesis, starting from inactive precursor proteins (prelantibiotics). The latter are post‐translationally converted into the active peptide antibiotics through enzymic modifications. The modifying enzymes effect dehydrations at the serine and threonine residues and stereospecific additions of the cysteine thiol groups to the resulting α,β‐unsaturated double bonds, which lead to the formation of several sulfide bridges. Upon subsequent proteolytic cleavage of the leader peptide, the biologically active lantibiotic is formed. Conformational analyses of the lantibiotics, as well as of their prepeptides, enables one to obtain information about the mechanism and steps of the biosynthesis. Antibodies against synthetic prepeptide sequences, and modern instrumental methods for the analysis of peptides, allow structural elucidation of the biosynthetic intermediates.