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
Shao, Zengyi; Zhao, Huimin (2014) Manipulating natural product biosynthetic pathways via DNA assembler. Curr Protoc Chem Biol 6:65-100
Cobb, Ryan E; Ning, Jonathan C; Zhao, Huimin (2014) DNA assembly techniques for next-generation combinatorial biosynthesis of natural products. J Ind Microbiol Biotechnol 41:469-77
Luo, Yunzi; Cobb, Ryan E; Zhao, Huimin (2014) Recent advances in natural product discovery. Curr Opin Biotechnol 30:230-7
Doroghazi, James R; Albright, Jessica C; Goering, Anthony W et al. (2014) A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol 10:963-8
Yu, Xiaomin; Price, Neil P J; Evans, Bradley S et al. (2014) Purification and characterization of phosphonoglycans from Glycomyces sp. strain NRRL B-16210 and Stackebrandtia nassauensis NRRL B-16338. J Bacteriol 196:1768-79
Wang, Meng; Beissner, Mirko; Zhao, Huimin (2014) Aryl-aldehyde formation in fungal polyketides: discovery and characterization of a distinct biosynthetic mechanism. Chem Biol 21:257-63
Agarwal, Vinayak; Peck, Spencer C; Chen, Jui-Hui et al. (2014) Structure and function of phosphonoacetaldehyde dehydrogenase: the missing link in phosphonoacetate formation. Chem Biol 21:125-35
Ju, Kou-San; Doroghazi, James R; Metcalf, William W (2014) Genomics-enabled discovery of phosphonate natural products and their biosynthetic pathways. J Ind Microbiol Biotechnol 41:345-56
Eriksen, Dawn T; Lian, Jiazhang; Zhao, Huimin (2014) Protein design for pathway engineering. J Struct Biol 185:234-42
Cioni, Joel P; Doroghazi, James R; Ju, Kou-San et al. (2014) Cyanohydrin phosphonate natural product from Streptomyces regensis. J Nat Prod 77:243-9

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