Abstract

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.

  Funding Agency

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

  Institution

Name
University of Illinois Urbana-Champaign
Department
Type
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820

  Publications

Parkinson, Elizabeth I; Tryon, James H; Goering, Anthony W et al. (2018) Discovery of the Tyrobetaine Natural Products and Their Biosynthetic Gene Cluster via Metabologenomics. ACS Chem Biol 13:1029-1037
Ulrich, Emily C; Bougioukou, Despina J; van der Donk, Wilfred A (2018) Investigation of Amide Bond Formation during Dehydrophos Biosynthesis. ACS Chem Biol 13:537-541
Wang, Bin; Guo, Fang; Dong, Shi-Hui et al. (2018) Activation of silent biosynthetic gene clusters using transcription factor decoys. Nat Chem Biol :
Goettge, Michelle N; Cioni, Joel P; Ju, Kou-San et al. (2018) PcxL and HpxL are flavin-dependent, oxime-forming N-oxidases in phosphonocystoximic acid biosynthesis in Streptomyces. J Biol Chem 293:6859-6868
Sun, H; Zhao, H; Ang, E L (2018) A coupled chlorinase-fluorinase system with a high efficiency of trans-halogenation and a shared substrate tolerance. Chem Commun (Camb) 54:9458-9461
McLaughlin, Martin I; van der Donk, Wilfred A (2018) Stereospecific Radical-Mediated B12-Dependent Methyl Transfer by the Fosfomycin Biosynthesis Enzyme Fom3. Biochemistry 57:4967-4971
Wang, Yajie; Ren, Hengqian; Zhao, Huimin (2018) Expanding the boundary of biocatalysis: design and optimization of in vitro tandem catalytic reactions for biochemical production. Crit Rev Biochem Mol Biol 53:115-129
Born, David A; Ulrich, Emily C; Ju, Kou-San et al. (2017) Structural basis for methylphosphonate biosynthesis. Science 358:1336-1339
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
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

Showing the most recent 10 out of 119 publications