Microorganisms produce a myriad array of natural products or secondary metabolites that are of biomedical and biotechnological importance. However, the discovery and sustainable production of these compounds are often limited by our capability to manipulate the biosynthetic genes or clusters in either the native or the heterologous host. To overcome this key limitation in the natural product biosynthesis research area, the overall goal of the proposed research is to develop synthetic biology approaches for discovery, characterization, and engineering of phosphonic acid natural products in microorganisms. Specifically, we will focus on the engineering of the FR-900098 and fosfomycin biosynthetic pathways in heterologous hosts and development of new synthetic biology approaches for discovery of novel phosphonic acid natural products from sequenced genomes.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM077596-08
Application #
8634114
Study Section
Special Emphasis Panel (ZRG1-BCMB-U)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
8
Fiscal Year
2014
Total Cost
$314,050
Indirect Cost
$102,131
Name
University of Illinois Urbana-Champaign
Department
Type
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Peck, Spencer C; van der Donk, Wilfred A (2017) Go it alone: four-electron oxidations by mononuclear non-heme iron enzymes. J Biol Inorg Chem 22:381-394
Olivares, Philip; Ulrich, Emily C; Chekan, Jonathan R et al. (2017) Characterization of Two Late-Stage Enzymes Involved in Fosfomycin Biosynthesis in Pseudomonads. ACS Chem Biol 12:456-463
Born, David A; Ulrich, Emily C; Ju, Kou-San et al. (2017) Structural basis for methylphosphonate biosynthesis. Science 358:1336-1339
Peck, Spencer C; Wang, Chen; Dassama, Laura M K et al. (2017) O-H Activation by an Unexpected Ferryl Intermediate during Catalysis by 2-Hydroxyethylphosphonate Dioxygenase. J Am Chem Soc 139:2045-2052
Zhang, Mingzi M; Qiao, Yuan; Ang, Ee Lui et al. (2017) Using natural products for drug discovery: the impact of the genomics era. Expert Opin Drug Discov 12:475-487
Si, Tong; Li, Bin; Comi, Troy J et al. (2017) Profiling of Microbial Colonies for High-Throughput Engineering of Multistep Enzymatic Reactions via Optically Guided Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry. J Am Chem Soc 139:12466-12473
Ren, Hengqian; Hu, Pingfan; Zhao, Huimin (2017) A plug-and-play pathway refactoring workflow for natural product research in Escherichia coli and Saccharomyces cerevisiae. Biotechnol Bioeng 114:1847-1854
Ren, Hengqian; Wang, Bin; Zhao, Huimin (2017) Breaking the silence: new strategies for discovering novel natural products. Curr Opin Biotechnol 48:21-27
Zhang, Mingzi M; Wong, Fong Tian; Wang, Yajie et al. (2017) CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol :
Wendt, Kristen E; Ungerer, Justin; Cobb, Ryan E et al. (2016) CRISPR/Cas9 mediated targeted mutagenesis of the fast growing cyanobacterium Synechococcus elongatus UTEX 2973. Microb Cell Fact 15:115

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