All organisms produce a host of compounds that are generally not required in primary metabolic processes, but play important regulatory functions. These secondary metabolites have been exploited by every civilization to enhance life and cure human diseases. We know these as hormones, antibiotics, antitumor agents, and antivirals. Since these metabolites can harm cells if produced in excess, or if present when a need for them does not exist, their production is often strictly regulated. An understanding of how cells synthesize and regulate the production of secondary metabolites is essential if one is to be able to exploit them as human therapeutic agents. Deazapurines are secondary metabolites that are derived from purines. This proposal outlines studies on the biosynthesis of deazapurine-containing secondary metabolites by bacteria. Our goal is to bring to fore the tools of genomics, molecular biology and enzymology to form the framework of how these metabolites are synthesized and to exploring the chemical transformations that underlies the biosynthesis of these molecules.

Public Health Relevance

Deazapurine-containing compounds are widely distributed in nature and have been shown to have clinically useful activities. Our goal is to understand the chemical transformations that underlie biosynthesis of these compounds in an effort to synthesize additional molecules with improved properties.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
Project #
Application #
Study Section
Macromolecular Structure and Function E Study Section (MSFE)
Program Officer
Anderson, Vernon
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Arizona
Schools of Arts and Sciences
United States
Zip Code
Skinner, Owen S; Havugimana, Pierre C; Haverland, Nicole A et al. (2016) An informatic framework for decoding protein complexes by top-down mass spectrometry. Nat Methods 13:237-40
Bruender, Nathan A; Wilcoxen, Jarett; Britt, R David et al. (2016) Biochemical and Spectroscopic Characterization of a Radical S-Adenosyl-L-methionine Enzyme Involved in the Formation of a Peptide Thioether Cross-Link. Biochemistry 55:2122-34
Nelp, Micah T; Song, Yang; Wysocki, Vicki H et al. (2016) A Protein-derived Oxygen Is the Source of the Amide Oxygen of Nitrile Hydratases. J Biol Chem 291:7822-9
Bandarian, Vahe; Drennan, Catherine L (2015) Radical-mediated ring contraction in the biosynthesis of 7-deazapurines. Curr Opin Struct Biol 35:116-24
Song, Yang; Nelp, Micah T; Bandarian, Vahe et al. (2015) Refining the Structural Model of a Heterohexameric Protein Complex: Surface Induced Dissociation and Ion Mobility Provide Key Connectivity and Topology Information. ACS Cent Sci 1:477-487
Miles, Zachary D; Myers, William K; Kincannon, William M et al. (2015) Biochemical and Spectroscopic Studies of Epoxyqueuosine Reductase: A Novel Iron-Sulfur Cluster- and Cobalamin-Containing Protein Involved in the Biosynthesis of Queuosine. Biochemistry 54:4927-35
Lajoie, Daniel M; Roberts, Sue A; Zobel-Thropp, Pamela A et al. (2015) Variable Substrate Preference among Phospholipase D Toxins from Sicariid Spiders. J Biol Chem 290:10994-1007
Bruender, Nathan A; Young, Anthony P; Bandarian, Vahe (2015) Chemical and Biological Reduction of the Radical SAM Enzyme 7-Carboxy-7-deazaguanine [corrected] Synthase. Biochemistry 54:2903-10
Nelp, Micah T; Bandarian, Vahe (2015) A Single Enzyme Transforms a Carboxylic Acid into a Nitrile through an Amide Intermediate. Angew Chem Int Ed Engl 54:10627-9
Young, Anthony P; Bandarian, Vahe (2015) Mechanistic Studies of the Radical S-Adenosyl-L-methionine Enzyme 4-Demethylwyosine Synthase Reveal the Site of Hydrogen Atom Abstraction. Biochemistry 54:3569-72

Showing the most recent 10 out of 31 publications