Discovery and structural characterization of lanthipeptides from soil and rumen bacteria

As members of the ribosomally synthesized and post-translationally modified peptide natural products (RiPPs), lanthipeptides possess myriad structural diversity and potential for discovery using genome-guided approaches. Biological activities of interest embedded within lanthipeptide structures include antimicrobial, antiviral, and morphogenetic functions. Continued discovery efforts seek to expand the characterized activities and structures of these compounds, as well as the enzymes that execute their biosynthesis. The contents of this thesis are focused on the discovery of lanthipeptides using a variety of methods. Chapters 2 and 4 demonstrate the application of heterologous expression of gene clusters to produce lanthipeptides. The resulting peptide structures and enzyme activities provide intriguing insights into diversity of biosynthetic approaches present in this class of compounds. Furthermore, the abundance of precursor peptides encoded in the lanthipeptide biosynthetic systems discussed in Chapters 2 and 4 offer examples of combinatorial biosynthesis and the tantalizing possibility to harness this attribute. In contrast, Chapter 3 provides a glimpse into the targeted screening of Actinobacteria for the production of lanthipeptides, which suggests additional structural diversity. The successful application of these methods increases the number of lanthipeptide compounds and systems, which ultimately allows for a deeper understanding of and appreciation for this class of natural products.

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

2017

Author dc:creator

• Zhao, Xi Ling

Contributors dc:contributor

• van der Donk, Wilfred A.
• Metcalf, William W.
• Mitchell, Douglas A.
• Sweedler, Jonathan V.

• Ribosomally synthesized and post-translationally modified peptide natural products (RiPPs)
• Lanthipeptides
• Heterologous expression of gene clusters
• Combinatorial biosynthesis

Statement dc:rights

• Copyright 2017 Xi Zhao

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/97537

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/97537