Phosphonic acids are a potent, yet underexploited, group of compounds with great promise in the treatment of human disease. Numerous structurally distinct phosphonates are produced in nature and many have useful bioactive properties. Importantly, the biological targets of phosphonic acids vary substantially, allowing them to be used for treating a variety of health conditions. The potent bioactivity of phosphonates also allows their use as fungicides, herbicides and pesticides. In our Initial funding period we showed that phosphonate biosynthesis is surprisingly common in nature and that a wealth of uncharacterized natural products await characterization. In this sub-project we propose a series of molecular, genetic and biochemical experiments aimed at exploiting and expanding these discoveries.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Program Projects (P01)
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Special Emphasis Panel (ZRG1-BCMB-U)
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University of Illinois Urbana-Champaign
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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
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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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