Lantibiotic Structures as Guidelines for the Design of Peptides That Can Be Modified by Lantibiotic Enzymes
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- 作者：Rick Rink ; Anneke Kuipers ; Esther de Boef ; Kees J. Leenhouts ; Arnold J. M. Driessen ; Gert N. Moll ; and Oscar P. Kuipers
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：June 21, 2005
- 年：2005
- 卷：44
- 期：24
- 页码：8873 - 8882
- 全文大小：186K
- 年卷期：v.44,no.24(June 21, 2005)
- ISSN：1520-4995
文摘
Lantibiotics are (methyl)lanthionine-containing bacterial peptides. (Methyl)lanthionines areposttranslationally introduced into the prepropeptides by biosynthetic enzymes that dehydrate serines andthreonines and couple these dehydrated residues to cysteine residues. Thirty seven lantibiotic primarystructures have been proposed to date, but little is known about the substrate specificity of the lantibioticmodifying enzymes. To define rules for the rational design of modified peptides, we compared all knownlantibiotic structures by in silico analysis. Although no strict sequence motifs can be defined that governthe modification, statistical analysis demonstrates that dehydratable serines and threonines are more oftenflanked by hydrophobic than by hydrophilic amino acids. Serine residues escape dehydration more oftenthan threonines. With these rules, novel hexapeptides were designed that either were predicted to becomemodified or will escape modification. The hexapeptides were fused to the nisin leader and expressed ina Lactococcus lactis strain containing the nisin modifying and export enzymes. The excreted peptideswere analyzed by mass spectrometry. All designed fusion peptides were produced, and the presence orabsence of modifications was found to be in full agreement with the predictions based on the statisticalanalysis. These findings demonstrate the feasibility of the rational design of a wide range of novel peptideswith dehydrated amino acid residues.