Specific Aims 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 #
2P01GM077596-06
Application #
8329255
Study Section
Special Emphasis Panel (ZRG1-BCMB-U (40))
Project Start
2007-04-10
Project End
2017-03-31
Budget Start
2012-04-10
Budget End
2013-03-31
Support Year
6
Fiscal Year
2012
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
Zhao, Huimin; Medema, Marnix H (2016) Standardization for natural product synthetic biology. Nat Prod Rep 33:920-4
Chekan, Jonathan R; Cogan, Dillon P; Nair, Satish K (2016) Molecular Basis for Resistance Against Phosphonate Antibiotics and Herbicides. Medchemcomm 7:28-36
Zhang, Mingzi M; Wang, Yajie; Ang, Ee Lui et al. (2016) Engineering microbial hosts for production of bacterial natural products. Nat Prod Rep 33:963-87
Goering, Anthony W; McClure, Ryan A; Doroghazi, James R et al. (2016) Metabologenomics: Correlation of Microbial Gene Clusters with Metabolites Drives Discovery of a Nonribosomal Peptide with an Unusual Amino Acid Monomer. ACS Cent Sci 2:99-108
Ulrich, Emily C; van der Donk, Wilfred A (2016) Cameo appearances of aminoacyl-tRNA in natural product biosynthesis. Curr Opin Chem Biol 35:29-36
Freestone, Todd S; Zhao, Huimin (2016) Combinatorial pathway engineering for optimized production of the anti-malarial FR900098. Biotechnol Bioeng 113:384-92
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
Luo, Yunzi; Enghiad, Behnam; Zhao, Huimin (2016) New tools for reconstruction and heterologous expression of natural product biosynthetic gene clusters. Nat Prod Rep 33:174-82
Peck, Spencer C; van der Donk, Wilfred A (2016) Go it alone: four-electron oxidations by mononuclear non-heme iron enzymes. J Biol Inorg Chem :
Blodgett, Joshua Av; Zhang, Jun Kai; Yu, Xiaomin et al. (2016) Conserved biosynthetic pathways for phosalacine, bialaphos and newly discovered phosphonic acid natural products. J Antibiot (Tokyo) 69:15-25

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