Siezen R J, Kuipers O P, de Vos W M
Dept. of Biophysical Chemistry, Netherlands Institute for Dairy Research.
Antonie Van Leeuwenhoek. 1996 Feb;69(2):171-84. doi: 10.1007/BF00399422.
Lantibiotics form a group of modified peptides with unique structures, containing post-translationally modified amino acids such as dehydrated and lanthionine residues. In the gram-positive bacteria that secrete these lantibiotics, the gene clusters flanking the structural genes for various linear (type A) lantibiotics have recently been characterized. The best studied representatives are those of nisin (nis), subtilin (spa), epidermin (epi), Pep5 (pep), cytolysin (cyl), lactocin S (las) and lacticin 481 (lct). Comparison of the lantibiotic gene clusters shows that they contain conserved genes that probably encode similar functions. The nis, spa, epi and pep clusters contain lanB and lanC genes that are presumed to code for two types of enzymes that have been implicated in the modification reactions characteristic of all lantibiotics, i.e. dehydration and thio-ether ring formation. The cyl, las and lct gene clusters have no homologue of the lanB gene, but they do contain a much larger lanM gene that is the lanC gene homologue. Most lantibiotic gene clusters contain a lanP gene encoding a serine protease that is presumably involved in the proteolytic processing of the prelantibiotics. All clusters contain a lanT gene encoding an ABC transporter likely to be involved in the export of (precursors of) the lantibiotics. The lanE, lanF and lanG genes in the nis, spa and epi clusters encode another transport system that is possibly involved in self-protection. In the nisin and subtilin gene clusters two tandem genes, lanR and lanK, have been located that code for a two-component regulatory system. Finally, non-homologous genes are found in some lantibiotic gene clusters. The nisI and spaI genes encode lipoproteins that are involved in immunity, the pepI gene encodes a membrane-located immunity protein, and epiD encodes an enzyme involved in a post-translational modification found only in the C-terminus of epidermin. Several genes of unknown function are also found in the las gene cluster. A database has been assembled for all putative gene products of type A lantibiotic gene clusters. Database searches, multiple sequence alignment and secondary structure prediction have been used to identify conserved sequence segments in the LanB, LanC, LanE, LanF, LanG, LanK, LanM, LanP, LanR and LanT gene products that may be essential for structure and function. This database allows for a rapid screening of newly determined sequences in lantibiotic gene clusters.
羊毛硫抗生素是一组具有独特结构的修饰肽，含有翻译后修饰的氨基酸，如脱水氨基酸和羊毛硫氨酸残基。在分泌这些羊毛硫抗生素的革兰氏阳性细菌中，各种线性（A型）羊毛硫抗生素结构基因两侧的基因簇最近已得到表征。研究得最透彻的代表是乳链菌肽（nis）、枯草菌素（spa）、表皮菌素（epi）、Pep5（pep）、溶细胞素（cyl）、乳酸链球菌素S（las）和乳酸乳球菌素481（lct）。羊毛硫抗生素基因簇的比较表明，它们含有可能编码相似功能的保守基因。nis、spa、epi和pep基因簇包含lanB和lanC基因，推测这两个基因编码两种酶，这些酶参与了所有羊毛硫抗生素特有的修饰反应，即脱水和硫醚环形成。cyl、las和lct基因簇没有lanB基因的同源物，但它们确实包含一个大得多的lanM基因，该基因与lanC基因同源。大多数羊毛硫抗生素基因簇包含一个lanP基因编码丝氨酸蛋白酶，推测该酶参与前体羊毛硫抗生素的蛋白水解加工。所有基因簇都包含一个lanT基因，编码一个ABC转运蛋白，可能参与羊毛硫抗生素（前体）的输出。nis、spa和epi基因簇中的lanE、lanF和lanG基因编码另一种可能参与自我保护的转运系统。在乳链菌肽和枯草菌素基因簇中定位了两个串联基因lanR和lanK，它们编码一个双组分调节系统。最后，在一些羊毛硫抗生素基因簇中发现了非同源基因。nisI和spaI基因编码参与免疫的脂蛋白，pepI基因编码一种位于膜上的免疫蛋白，epiD编码一种仅参与表皮菌素C末端翻译后修饰的酶。在las基因簇中还发现了几个功能未知的基因。已为A型羊毛硫抗生素基因簇的所有推定基因产物建立了一个数据库。通过数据库搜索、多序列比对和二级结构预测，已鉴定出LanB、LanC、LanE、LanF、LanG、LanK、LanM、LanP、LanR和LanT基因产物中可能对结构和功能至关重要的保守序列片段。该数据库允许快速筛选羊毛硫抗生素基因簇中新测定的序列。
