Audrey Lamb

Associate Professor
Ph.D., Vanderbilt University, 1998
Post doctoral fellow, Northwestern University, 1998-2002
785-864-5075
5060 Haworth Hall

Structural and functional analysis of enzymes associated with iron uptake.

With the exception of a few microbial organisms, iron is required for life on earth.  Iron serves as an important cofactor for a variety of enzymes that perform crucial reactions, including roles in cellular respiration, nucleic acid synthesis, and resistance to reactive oxygen intermediates.  Fe(III) is very insoluble and frequently biologically inaccessible such that the concentration of available iron in the human host is ~10-9 mM.  Since a typical pathogenic bacterium requires ~1 mM iron for optimal growth, these organisms have developed elaborate systems to scavenge iron from the host.  The pathogens that we study use low molecular weight iron chelators called siderophores.  The bacteria synthesize, secrete, and then selectively take up the iron-loaded siderophore to colonize human tissues.  Non-ribosomal peptide synthetases (NRPSs) and their accessory proteins are a fascinating collection of enzymes required for the production of these bioactive peptides.  Siderophore biosynthetic enzymes are found in plants, fungi and bacteria, frequently having no human homologues, making them attractive targets for the development of new antimicrobial compounds.  The goal of the lab is to understand the structure-function relationships that drive the biosynthesis of siderophores, compounds linked to virulence and pathogenesis in a variety of deadly bacteria.  The ultimate outcome of the work will be the structural biology and mechanistic enzymology required for the development of new antibiotics to fight many bacterial infections, including P. aeruginosa, an opportunistic pathogen that is problematic for cystic fibrosis and other susceptible patients, as well as for bacteria that generate chemically-related siderophores such as Yersinia pestis (plague), Vibrio cholera (cholera) and Mycobacterium tuberculosis (tuberculosis).  The enzymes we study are also of interest to the protein engineering community, as many bioactive peptides contain similar chemical moieties and homologous enzymes are found in biosynthetic pathways of a variety of natural products.  Two examples are epothilone and cyclosporin.  Therefore, our work may also impact the design of new anti-cancer and immunosuppressive therapeutics.

 

Representative Publications

 

Search PubMed for articles by Audrey L. Lamb.


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Kathy Meneely (postdoctoral fellow, Lamb lab) presented a poster entitled “Structure informs on function: A thiazolinyl imine reductase of siderophore biosynthesis” at the Second Annual Symposium on Structural Biology sponsored by the Oklahoma Center for Biomedical Research Excellence in Structural Biology at the University of Oklahoma on June 9. http://structuralbiology.ou.edu/symposium
Symposium
Registration is free but early registration is strongly encouraged as we are capacity-limited to 100 participants. Please register no later than May 28th via this on-line registration page if you plan to attend. Registration is now closed (the symposium is full).