Brian O. Bachmann, Ph.D.

Faculty Appointments
Co-Director of the Program in Biochemistry and Chemical Biology Professor of Chemistry Professor of BiochemistryProfessor of Pharmacology
Ph.D., Chemistry, Bioorganic, Johns Hopkins University, Baltimore, MarylandM.A., CHEMISTRY, Johns Hopkins University, Baltimore, MarylandM.S., Southern Methodist University, Dallas, TexasB.S., Virginia Polytechnic Institute, Blacksburg, Virginia
Office Address
Vanderbilt University
Chemistry Department
12435J MRB IV
Nashville, TN 37235
Research Description
Research in the Vanderbilt Laboratory for Biosynthetic studies (PI, Brian O. Bachmann) concerns itself with three main topics:

* How does nature assemble molecules?

* What are the boundaries of moleclular diversity accessible by natural processes?

* How can we harness our understanding of these molecular proceses, their limitations and potential towards the ultimate goal of engineering the biosynthesis of any molecule imaginable?

Natural product biosynthetic pathway elucidation studies have traditionally focused on the stepwise dissection of the biochemical and genetic mechanisms of natural product assembly in vivo. We are elaborating on these studies, with a focus on the biosynthesis of pharmacophores of relevance to human health and we are particularly interested in pharmacophores which present challenges to chemical synthesis.

Currently, we are investigating the biosynthesis of alpa-aminophosphonates, which are potent inhibitors of zinc-metaloproteinase enzymes. We are also investigating the biosynthesis of benzodiazepines and orthosomycin type oligosaccharides.

Metabolic pathway engineering studies have emphasized the assembly and modification of biosynthetic pathways to produce to improve pathways for the production of existing compounds. Our vision is to apply the natural product biosyntheitc design rules the biosynthetic community has explored over the previous decades towards the synthesis of non-natural compounds of value to academic and industrial communities. What are the limitations and potential for total synthesis practiced in vivo?

Natural product discovery studies expand upon the structure/activity space of known chemical entities. We are developing a program in natural product discovery from highly unusual microbial sources. The goal of this program is drug discovery of novel chemical with antimicrobial activity.
Research Keywords
Biosynthesis of bioactive secondary metabolites.
Scism RA, Stec DF, Bachmann BO. Synthesis of nucleotide analogues by a promiscuous phosphoribosyltransferase. Org. Lett [print-electronic]. 2007 Oct 10/11/2007; 9(21): 4179-82. PMID: 17854193, DOI: 10.1021/ol7016802, ISSN: 1523-7060.

Bachmann BO. Foundations for directed alkaloid biosynthesis. Chem. Biol. 2007 Aug; 14(8): 875-6. PMID: 17719485, PII: S1074-5521(07)00256-6, DOI: 10.1016/j.chembiol.2007.08.001, ISSN: 1074-5521.

Hu Y, Phelan V, Ntai I, Farnet CM, Zazopoulos E, Bachmann BO. Benzodiazepine biosynthesis in Streptomyces refuineus. Chem. Biol. 2007 Jun; 14(6): 691-701. PMID: 17584616, PII: S1074-5521(07)00178-0, DOI: 10.1016/j.chembiol.2007.05.009, ISSN: 1074-5521.

Ntai I, Phelan VV, Bachmann BO. Phosphonopeptide K-26 biosynthetic intermediates in Astrosporangium hypotensionis. Chem. Commun. (Camb.). 2006 Nov 11/21/2006; (43): 4518-20. PMID: 17283804, ISSN: 1359-7345.

Sulikowski MM, Bachmann BO. Designing a curriculum that goes beyond a list of topics. ACS Chem. Biol. 2006 Sep 9/19/2006; 1(8): 489-91. PMID: 17168533, DOI: 10.1021/cb6003178, ISSN: 1554-8937.

Wilkinson B, Bachmann BO. Biocatalysis in pharmaceutical preparation and alteration. Curr Opin Chem Biol [print-electronic]. 2006 Apr; 10(2): 169-76. PMID: 16500136, PII: S1367-5931(06)00028-7, DOI: 10.1016/j.cbpa.2006.02.006, ISSN: 1367-5931.

Bachmann BO. Decoding chemical structures from genomes. Nature chemical biology. 2005 Oct; 1(5) Sect. 244,5.

Ntai I, Manier ML, Hachey DL, Bachmann BO. Biosynthetic origins of C-P bond containing tripeptide K-26. Org. Lett. 2005 Jun 6/23/2005; 7(13): 2763-5. PMID: 15957941, DOI: 10.1021/ol051091d, ISSN: 1523-7060.

McAlpine JB, Bachmann BO, Piraee M, Tremblay S, Alarco AM, Zazopoulos E, Farnet CM. Microbial genomics as a guide to drug discovery and structural elucidation: ECO-02301, a novel antifungal agent, as an example. J. Nat. Prod. 2005 Apr; 68(4): 493-6. PMID: 15844935, DOI: 10.1021/np0401664, ISSN: 0163-3864.

Zazopoulos E, Huang K, Staffa A, Liu W, Bachmann BO, Nonaka K, Ahlert J, Thorson JS, Shen B, Farnet CM. A genomics-guided approach for discovering and expressing cryptic metabolic pathways. Nat. Biotechnol [print-electronic]. 2003 Feb; 21(2): 187-90. PMID: 12536216, PII: nbt784, DOI: 10.1038/nbt784, ISSN: 1087-0156.

Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC. The catalytic cycle of beta -lactam synthetase observed by x-ray crystallographic snapshots. Proc. Natl. Acad. Sci. U.S.A [print-electronic]. 2002 Nov 11/12/2002; 99(23): 14752-7. PMID: 12409610, PMCID: PMC137491, PII: 232361199, DOI: 10.1073/pnas.232361199, ISSN: 0027-8424.

Ahlert J, Shepard E, Lomovskaya N, Zazopoulos E, Staffa A, Bachmann BO, Huang K, Fonstein L, Czisny A, Whitwam RE, Farnet CM, Thorson JS. The calicheamicin gene cluster and its iterative type I enediyne PKS. Science. 2002 Aug 8/16/2002; 297(5584): 1173-6. PMID: 12183629, PII: 297/5584/1173, DOI: 10.1126/science.1072105, ISSN: 1095-9203.

Miller MT, Bachmann BO, Townsend CA, Rosenzweig AC. Structure of beta-lactam synthetase reveals how to synthesize antibiotics instead of asparagine. Nat. Struct. Biol. 2001 Aug; 8(8): 684-9. PMID: 11473258, PII: 90394, DOI: 10.1038/90394, ISSN: 1072-8368.

Zhou J, Kelly WL, Bachmann BO, Gunsior M, Townsend CA, Solomon EI. Spectroscopic studies of substrate interactions with clavaminate synthase 2, a multifunctional alpha-KG-dependent non-heme iron enzyme: correlation with mechanisms and reactivities. J. Am. Chem. Soc. 2001 Aug 8/1/2001; 123(30): 7388-98. PMID: 11472170, PII: ja004025+, ISSN: 0002-7863.

Bachmann BO, Townsend CA. Kinetic mechanism of the beta-lactam synthetase of Streptomyces clavuligerus. Biochemistry. 2000 Sep 9/19/2000; 39(37): 11187-93. PMID: 10985764, PII: bi000709i, ISSN: 0006-2960.

Zhou, J., M. Gunsior, B. O. Bachmann, W. L. Kelly, E. G. Pavel, R. W. Busby, C. A. Townsend, and E. I. Solomon. Spectroscopic studies of substrates and cosubstrate binding to the alha-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: correlation to reactivities and mechanisms. Journal of Inorganic Biochemistry. 1999; 74: 350.

Bachmann BO, Li R, Townsend CA. Beta-Lactam synthetase: a new biosynthetic enzyme. Proc. Natl. Acad. Sci. U.S.A. 1998 Aug 8/4/1998; 95(16): 9082-6. PMID: 9689037, PMCID: PMC21295, ISSN: 0027-8424.

Zhou, J., M. Gunsior, B. O. Bachmann, C. A. Townsend, and E. I. Solomon. Substrate binding to the alpha-ketoglutarate-dependent non-heme iron enzyme clavaminate synthase 2: Coupling mechanism of oxidative decarboxylation and hydroxylation. J. Am. Chem. Soc. 1998; 120: 13539-40.

Buynak, J. D., A. S. Rao, G. P. Ford, C. Carver, G. Adam, B. Geng, B. Bachmann, S. Shobassy, and S. Lackey. 7-alkylidenecephalosporin esters as inhibitors of human leukocyte elastase. J. Med. Chem. 1997; 40: 3423-343.

Buynak, J. D., K. C. Wu, B. Bachmann, D. Khasnis, L. Hua, H. K. Nguyen, and C. L. Carver.. Synthesis and Biological-Activity of 7-Alkylidenecephems. J. Med. Chem. 1995; 38: 1022-34.

Buynak, J. D., B. Geng, B. Bachmann, and L. Hua.. The Synthesis and Beta-Lactamase Inhibitory Activity of 6-(Carboxymethylene)Penicillins and 7-(Carboxymethylene) Cephalosporins. Bioorg. Med. Chem. Lett. 1995; 5: 1513-8.

Buynak, J. D., D. Khasnis, B. Bachmann, K. C. Wu, and G. Lamb.. Synthesis and Mechanistic Evaluation of 7-Vinylidenecephem Sulfones as Beta-Lactamase Inhibitors. J. Am. Chem. Soc. 1994; 116: 10955-65.

Hudlicky, T., M. Mandel, J. Rouden, R. S. Lee, B. Bachmann, T. Dudding, K. J. Yost, and J. S. Merola.. Microbial Oxidation of Aromatics in Enantiocontrolled Synthesis .1. Expedient and General Asymmetric-Synthesis of Inositols and Carbohydrates Via an Unusual Oxidation of a Polarized Diene with Potassium-Permanganate. 1994; 1553-67.