Subtilin biosynthesis

The presence of two genes, nisB and nisC, encoding 993- and 414-residue proteins without significant homology to other known proteins, but conserved in several lantibiotic operons, has made them strong candidates for post-trans-lational modifications in the maturation pathway of lantibiotics [40]. Limited similarity between NisB and E. coli IlvA, a threonine dehydratase, was reported and hence a dehydratase function for NisB was suggested [40]. Mutation studies of NisB, NisC, EpiB, EpiC, and SpaB indicated that these proteins were essential for nisin, epidermin and subtilin biosynthesis, respectively [40,86,87,190]. As no precursors have been identified and characterized in these mutants, conclusions about the reaction that is catalyzed by these proteins remain speculative [40]. Secondary-structure predictions and experimental evidence confirmed that NisB and SpaB are both membrane-bound [100]. 

Klein, C. Kaletta, C. Entian, K.D. Biosynthesis of the lantibiotic subtilin is regulated by a histidine kinase/response regulator system. Appl. Environ. Microbiol., 59, 296-303 (1993)... 

A large number of a, 3-didehydro-a-amino acids have been identified as constituents of relatively low molecular weight cyclic compounds from microbial sources. However, the presence of a,p-didehydroalanine in bacterial as well as in mammalian histidine ammonia lyase and in phenylalanine ammonia lyase shows that the occurrence of a,p-didehydro-a-amino acids is not limited to small molecules alone 8 These residues are incorporated in natural sequences by posttranslation modification. a,p-Didehydro-a-amino acids have also been postulated to be precursors in the biosynthesis of several heterocyclic metabolites including penicillin and cephalosporin 9 Other well-known compounds containing ,( -di-dehydro-a-amino acids are nisin 10,11 (a food preservative112 ), subtilin (a broad spectrum antibiotic) 13 and some of the metabolites isolated from Streptomyces strains such as gri-seoviridin 14 ... 

Klein C, Kaletta C, SchneU N, Entian K-D (1992) Analysis of genes involved in the biosynthesis of the lantibiotic subtilin. Appl Environ Microbiol 58 132 -142... 

Gutowski Eckel Z, Klein C, Siegers K, Bohm K. Hammelmann M, Emian KD. Growth phast dependent regulation and membrane localization of SpaB, a protein involved in biosynthesis of the laniibioitc subtilin. Appl Environ Microbiol 1994 60 1-11. 

Ramseier HR. The action of nisin on Clostridium ixxulinum. Arch Mikrobiol I960 37 57-94. Hansen JN. Chung YJ, Liu W, Steen MJ. Biosynthesis and mechanism of action of nisin and subtilin. Jung C, Sahl H-G, eds. Nisin and Novel Lantibiotics. Leiden, The Netherlands ESCOM, 1991 287-302. 

The biosynthesis of the heterodetic rings in the antibiotics nisin and subtilin corresponds exactly to the steric course of this cysteine formation from dehydroalanine within a peptide. 

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