Abstract

A research program is described that will continue biosynthetic studies with the nocardicins, the prototype monocyclic Beta-lactam antibiotic, and clavulanic acid, a potent inhibitor of bacterial beta-lactamases. These studies are to be extended to the remarkable antipodal clavams and to the medicinally important carbapenems using carbapenem-3-carboxylic acid as the experimental system. In collaboration with workers at Eli Lilly, biosynthetic investigation of the glycopeptide antibiotics represented by vancomycin will be initiated. The potential role of beta-oxidized amino acids will be examined in clavulanic acid, carbapenems (and gamma-oxidized in clavams) and further developed in new studies of the C-nucleoside antibiotics showdomycin and pyrazofurin.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI014937-10
Application #
3125941
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1978-09-01
Project End
1989-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
10
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Type
Schools of Arts and Sciences
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

Long, Darcie H; Townsend, Craig A (2018) Mechanism of Integrated ?-Lactam Formation by a Nonribosomal Peptide Synthetase during Antibiotic Synthesis. Biochemistry 57:3353-3358
Oliver, Ryan A; Li, Rongfeng; Townsend, Craig A (2018) Monobactam formation in sulfazecin by a nonribosomal peptide synthetase thioesterase. Nat Chem Biol 14:5-7
Li, Rongfeng; Oliver, Ryan A; Townsend, Craig A (2017) Identification and Characterization of the Sulfazecin Monobactam Biosynthetic Gene Cluster. Cell Chem Biol 24:24-34
Harari, Colin M; Magagna, Michelle; Bedoya, Mariajose et al. (2016) Microwave Ablation: Comparison of Simultaneous and Sequential Activation of Multiple Antennas in Liver Model Systems. Radiology 278:95-103
Townsend, Craig A (2016) Convergent biosynthetic pathways to ?-lactam antibiotics. Curr Opin Chem Biol 35:97-108
Marous, Daniel R; Lloyd, Evan P; Buller, Andrew R et al. (2015) Consecutive radical S-adenosylmethionine methylations form the ethyl side chain in thienamycin biosynthesis. Proc Natl Acad Sci U S A 112:10354-8
Gaudelli, Nicole M; Long, Darcie H; Townsend, Craig A (2015) ?-Lactam formation by a non-ribosomal peptide synthetase during antibiotic biosynthesis. Nature 520:383-7
Gaudelli, Nicole M; Townsend, Craig A (2014) Epimerization and substrate gating by a TE domain in ?-lactam antibiotic biosynthesis. Nat Chem Biol 10:251-8
Buller, Andrew R; Freeman, Michael F; Schildbach, Joel F et al. (2014) Exploring the role of conformational heterogeneity in cis-autoproteolytic activation of ThnT. Biochemistry 53:4273-81
Li, Rongfeng; Lloyd, Evan P; Moshos, Kristos A et al. (2014) Identification and characterization of the carbapenem MM 4550 and its gene cluster in Streptomyces argenteolus ATCC 11009. Chembiochem 15:320-31

Showing the most recent 10 out of 56 publications