Lichenicidin biosynthesis: LicP protease specificity

• Autor(a) principal: Faria, Raquel Cristina Laranjeira
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10773/7460
• topic: Microbiologia; Antibióticos; Proteases; Péptidos

The lantibiotics are ribosomally synthesized peptides produced by Gram-positive cells that have antibiotic or morphogenic activity. After translation, the lantibiotics undergo chemical changes that result in the formation of unusual amino acids (lanthionine and methylanthionine), as well as the establishment of chemical bonds that confer a polycyclic structure to the peptide chain. After modifications occur, the leader sequence of the prelantibiotic is removed to yield the active lantibiotic, a process that may involve a single proteolitical reaction or two consecutive reactions. The lantibiotics are divided into classes according to their mechanism of biosynthesis and its biological activity. A particular sub-class of such compounds consists of two-component lantibiotics, in which each lantibiotic consists of two peptides, α and β, which act in synergy to confer it full activity. Lichenicidin is a two component lantibiotic produced by a microorganism commonly found in soil, Bacillus licheniformis. The leader sequence of one of the lichenicidin peptides (α-peptide) is totally removed through a single proteolytic reaction while the formation of the second peptide (β-peptide) implies the occurrence of two reactions of proteolysis, presumably made by the successive action of two enzymes, LicT and LicP, encoded in B. licheniformis genome. In this work, we evaluated the specificity of the LicP protease. For this purpose, we produced β-peptide mutants, in which some amino acids were replaced by Ala. The results indicated that LicP functionality is not impaired by single amino acid replacements. It was also shown that the Bliβ maturation process should, indeed, include the proteolysis of the leader sequence before the activity of LicP since an introduced mutation in the LicT cleavage site most probably inhibited the Bliβ full maturation.