Development and application of synthetic biology tools for natural product research
type: CreativeWork
description: Natural products, or secondary metabolites, usually refer to bioactive small molecules produced by microorganisms or plants. To date, thousands of natural products have been characterized which reveal diverse structures and bioactivities, making it an ideal resource for discovering drug leads and mining biocatalysts. The advances in bioinformatics and DNA sequencing technology in the 21st century enables the prediction of tremendously large numbers of biosynthetic pathways for natural products directly from genomic database, which indicates Nature’s great potential of making these molecules remains to be explored. However, most of these uncharacterized pathways are naturally under negative regulation or encoded by uncultivable microorganisms and thus turn into “dark matters” for natural product discovery. Pathway refactoring serves as an invaluable synthetic biology tool for natural product discovery, characterization, and engineering. However, the complicated and laborious molecular biology techniques largely hinder its application in natural product research, especially in a high-throughput manner. Therefore, I developed a plug-and-play pathway refactoring workflow for high-throughput, flexible pathway construction, and expression in both Escherichia coli and Saccharomyces cerevisiae. The modular design not only enables the system to accommodate pathways with different number of genes, but also facilitates gene deletion and replacement. As proof of concept, a total of 96 pathways for combinatorial carotenoid biosynthesis were built successfully. The plug-and-play workflow was then used for discovering lanthipeptides and glycocins, both are groups of ribosomally synthesized post-translationally modified peptides (RiPPs) with various antimicrobial activities. A Class IV lanthipeptide with an unusual ring topology was successfully discovered, and its cyclization mechanism was elucidated in vitro. In addition, four novel glycocins were also discovered and one of them …
abstract: Natural products, or secondary metabolites, usually refer to bioactive small molecules produced by microorganisms or plants. To date, thousands of natural products have been characterized which reveal diverse structures and bioactivities, making it an ideal resource for discovering drug leads and mining biocatalysts. The advances in bioinformatics and DNA sequencing technology in the 21st century enables the prediction of tremendously large numbers of biosynthetic pathways for natural products directly from genomic database, which indicates Nature’s great potential of making these molecules remains to be explored. However, most of these uncharacterized pathways are naturally under negative regulation or encoded by uncultivable microorganisms and thus turn into “dark matters” for natural product discovery. Pathway refactoring serves as an invaluable synthetic biology tool for natural product discovery, characterization, and engineering. However, the complicated and laborious molecular biology techniques largely hinder its application in natural product research, especially in a high-throughput manner. Therefore, I developed a plug-and-play pathway refactoring workflow for high-throughput, flexible pathway construction, and expression in both Escherichia coli and Saccharomyces cerevisiae. The modular design not only enables the system to accommodate pathways with different number of genes, but also facilitates gene deletion and replacement. As proof of concept, a total of 96 pathways for combinatorial carotenoid biosynthesis were built successfully. The plug-and-play workflow was then used for discovering lanthipeptides and glycocins, both are groups of ribosomally synthesized post-translationally modified peptides (RiPPs) with various antimicrobial activities. A Class IV lanthipeptide with an unusual ring topology was successfully discovered, and its cyclization mechanism was elucidated in vitro. In addition, four novel glycocins were also discovered and one of them …
author: Ren, Hengqian
language: en
keywords: Natural Product, Synthetic Biology, Glycocin, Lanthipeptide, Polyketide
date published: 2019-08-23T20:44:36Z
date modified: 2026-07-22T22:24:44Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/105150