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Brian O. Bachmann

Title and Contact Information

Associate Professor of Chemistry
7330 Stevenson Center
Vanderbilt University
Nashville, TN 37235
Email   •   Website

Education

Ph.D., Johns Hopkins University, 2000

Specialties

VICB
Synthetic Biology
Organic Chemistry
Natural Products
Mechanistic Enzymology
Chemical Biology
Biosynthesis
Biochemistry

In the News

Vanderbilt View-Chemist discovers research is more fun underground
NIH-Drugs from deep down
BBC News-Brian Bachmann found bacteria in caves that could help develop future antibiotics
Research News @ Vanderbilt-New tool for mining bacterial genome for novel drugs

brian bachmann

Research

The primary mission of the Bachmann Lab is to apply knowledge of the design rules for secondary metabolism at the chemical, biochemical and genetic levels toward the biosynthesis of "non-natural" compounds of high value to biomedical research and the clinic. Key to this program in "synthetic biology" is the dissection of the mechanisms by which life makes bioactive molecules in vivo. The lab is organized according to three interlocking research areas: Biosynthesis, Synthetic Biology, and Discovery. These subgroups each have basic research and applied components and overlap with one another both thematically and methodologically.

Biosynthesis

The focus of the biosynthesis research subgroup centers on investigating the biosynthesis of pharmacophores by microorganisms from a genetic to a chemical basis. In all cases, we target non-trivial biotransformations that have little or no precedent in prior research. To date, pathways have been targeted in the bacterial Order Actinomycetales (also called actinomycetes), one of the richest microbial sources of secondary metabololites.

Synthetic Biology

Synthetic Biology is a burgeoning field, the ambitious aim of which is to use the machinery of biological systems (DNA, RNA, proteins) for the production of synthetic compounds and materials of high value to research, medicine and human life. For small molecule synthesis, these methods offer totally new avenues for the production of compounds and an alternative to petrochemical-based chemical synthesis. We believe that the global societal impacts of synthetic biology will be far reaching in this century. The primary mission of the Bachmann lab is to apply this knowledge of the design rules for secondary metabolism at the chemical, biochemical and genetic levels toward the biosynthesis of "non-natural" compounds of high value to bio research and the clinic.

Drug Discovery

It is becoming increasingly apparent that natural products derived from microbes, plants and animals represent important contributors of chemical diversity for the development of sustainable drug discovery efforts. Brian Bachmann in his former (industrial) and current (academic) lab has developed a two-pronged approach for natural product discovery:

1. A strategy for leveraging microbial genomic sequence data to predict secondary metabolic potential of microorganisms and to utilizing these predictions to prioritize isolations, accelerate isolation and structural elucidations.

2. A strategy for integrating natural product discovery into contemporary high throughput screening technologies by A) rapid generation of natural product fraction libraries from unique biological sources and B) applied metabolomics technologies for the identification and discovery of antibiotic/cytotoxic compounds. Rapid identification of compounds correlated to a biological activity of interest drives the prioritization of a classic isolation/structure-elucidation cascade in the Bachmann lab.

Selected Publications

Goodwin, C. R., Fenn, L. S., Derewacz, D. K., Bachmann, B. O., McLean, J. A. Structural Mass Spectrometry: Rapid Methods for Separation and Analysis of Peptide Natural Products. Journal of Natural Products. 2012, 67 (35): 48-53.

Iverson, T. M., Panosian, T. D., Birmingham, W. R., Nannemann, D. P., Bachmann, B. O. Molecular Differences between a Mutase and a Phosphatase: Investigations of the Activation Step in Bacillus cereus Phosphopentomutase. Biochemistry. 2012, 51 (9): 1964-1975.

Du, Y., Derewacz, D. K., Deguire, S. M., Teske, J., Ravel, J., Sulikowski, G. A. Biosynthesis of the apoptolidins in Nocardiopsis sp FU 40. Tetrahedron. 2011, 67 (35): 6568-6575.

Panosian, T. D., Nannemann, D. P., Watkins, G. R., Phelan, V. V., McDonald, W. H., Wadzinski, B. E., Bachmann, B. O., Iverson, T. M. Bacillus cereus Phosphopentomutase Is an Alkaline Phosphatase Family Member That Exhibits an Altered Entry Point into the Catalytic Cycle. Journal of Biological Chemistry. 2011, 286 (10): 8043-8054.

Nannemann, D. P., Birmingham, W. R., Scism, R. A., Bachmann, B. O. Assessing directed evolution methods for the generation of biosynthetic enzymes with potential in drug biosynthesis. Future Medicinal Chemistry. 2011, 3 (7): 803-819.

Bachmann, B. O., McNees, R., Melancon, B. J., Ghidu, V. P., Clark, R., Crews, B. C., DeGuire, S. M., Marnett, L. J., Sulikowski, G. A. Light-Induced Isomerization of Apoptolidin A leads to Inversion of C2-C3 Double Bond Geometry. Organic Letters. 2010, 12 (13): 2944-2947.

Panosian, T. D., Nannemann, D. P., Bachmann, B. O., Iverson, T. M. Crystallization and preliminary X-ray analysis of a phosphopentomutase from Bacillus cereus. ACTA Crystallographica Section F-Structural Biology and Crystallization Communications. 2010, 66: 811-814.

Akif, M., Ntai, I., Sturrock, E. D., Isaac, R. E., Bachmann, B. O., Acharya, K. R. Crystal structure of a phosphonotripeptide K-26 in complex with angiotensin converting enzyme homologue (AnCE) from Drosophila melanogaster. Biochemical and Biophysical Research Communications. 2010, 398 (3): 532-536.

Vey, J. L., Al-Mestarihi, A., Hu, Y., Funk, M. A., Bachmann, B. O., Iverson, T. M. Structure and Mechanism of ORF36, an Amino Sugar Oxidizing Enzyme in Everninomicin Biosynthesis. Biochemistry. 2010, 49(43): 9307-9317.

Scism, R. A., Bachmann, B. O. Five-Component Cascade Synthesis of Nucleotide Analogues in an Engineered Self-Immobilized Enzyme Aggregate. ChemBiochem. 2010, 11 (1): 67-70.

Bachmann, B. O., Ravel, J. Methods for in Silico Prediction of Microbial Polyketide and Nonribosomal Peptide Biosynthetic Pathways From DNA Sequence Data. Methods in Enzymology. 2009, 458: 181-217.

Phelan, VV., Du, Y., McLean, J. A., Bachmann, B. O. Adenylation Enzyme Characterization Using gamma-O-18(4)-ATP Pyrophosphate Exchange. Chemistry & Biology. 2009, 16 (5): 473-478.

Ghidu, V. P., Ntai, I., Wang, J. Q., Jacobs, A. T., Marnett, L. J., Bachmann B. O., Sulikowski, G. A. Combined Chemical and Biosynthetic Route to Access a New Apoptolidin Congener. Organic Letters. 2009, 11 (1): 3032-3034.

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