Investigations of the Substrate Specificity of Lacticin 481 Synthetase and Utilization in Peptide Engineering Applications

The promiscuous activity of LctM toward LctA prepeptides containing nonproteinogenic amino acids prompted the evaluation of LctM as a general catalyst for the introduction of post-translational modifications in non-lantibiotic peptides fused to the LctA leader peptide. LctM was utilized to efficiently introduce dehydrated, phosphorylated, and lanthionine cross-linked amino acids into therapeutically relevant non-lantibiotic peptides. Furthermore, enzymatically installed dehydro amino acids were used as sites of ligation with a variety of thiol nucleophiles for the preparation of peptide conjugates. Lastly, the role of the leader peptide in lacticin 481 biosynthesis was investigated. Surprisingly, the leader peptide was not required for dehydration activity of LctM, although it greatly enhanced the catalytic efficiency of LctM.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Levengood, Matthew

Contributors dc:contributor

• van der Donk, Wilfred A.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI3347436

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84328