Mechanistic dissection of the enzyme complexes involved in biosynthesis of lacticin 3147 and nisin

Appl Environ Microbiol. 2008 Nov;74(21):6591-7. doi: 10.1128/AEM.01334-08. Epub 2008 Sep 12.

Abstract

The thioether rings in the lantibiotics lacticin 3147 and nisin are posttranslationally introduced by dehydration of serines and threonines, followed by coupling of these dehydrated residues to cysteines. The prepeptides of the two-component lantibiotic lacticin 3147, LtnA1 and LtnA2, are dehydrated and cyclized by two corresponding bifunctional enzymes, LtnM1 and LtnM2, and are subsequently processed and exported via one bifunctional enzyme, LtnT. In the nisin synthetase complex, the enzymes NisB, NisC, NisT, and NisP dehydrate, cyclize, export, and process prenisin, respectively. Here, we demonstrate that the combination of LtnM2 and LtnT can modify, process, and transport peptides entirely different from LtnA2 and that LtnT can process and transport unmodified LtnA2 and unrelated peptides. Furthermore, we demonstrate a higher extent of NisB-mediated dehydration in the absence of thioether rings. Thioether rings apparently inhibited dehydration, which implies alternating actions of NisB and NisC. Furthermore, certain (but not all) NisC-cyclized peptides were exported with higher efficiency as a result of their conformation. Taken together, these data provide further insight into the applicability of Lactococcus lactis strains containing lantibiotic enzymes for the design and production of modified peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Bacteriocins / biosynthesis*
  • Enzymes / genetics
  • Enzymes / metabolism*
  • Lactococcus lactis / enzymology*
  • Models, Molecular
  • Nisin / biosynthesis*

Substances

  • Bacterial Proteins
  • Bacteriocins
  • Enzymes
  • lacticin 481
  • Nisin