This proposal is concerned with the molecular mechanisms that regulate the synthesis and degradation of membrane lipids in bacteria. The metabolism of two vitamins, lipoic acid and biotin, that are related to fatty acids are also studied. The general approach is to use genetics, biochemistry, and molecular biology to unravel these mechanisms and determine how the pathways are regulated. The mechanisms of fatty acid metabolism are highly conserved throughout metabolism thus giving these studies general applicability. However, in the case of fatty acid synthesis the details of the pathways differ sufficiently that compound that specifically inhibit the bacterial enzymes have been found. Therefore, bacterial fatty acid synthetic enzymes are excellent targets for new antibiotics. It should be noted that a group of protozon parasites including the malarial parasite have essential fatty acid synthetic enzymes that are closely related to the bacterial proteins and thus new antibiotic should prove effective versus these parasitic diseases. ? ?

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Microbial Physiology and Genetics Subcommittee 2 (MBC)
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Korpela, Jukka K
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
United States
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Cronan, John E (2018) Advances in synthesis of biotin and assembly of lipoic acid. Curr Opin Chem Biol 47:60-66
Manandhar, Miglena; Cronan, John E (2018) A Canonical Biotin Synthesis Enzyme, 8-Amino-7-Oxononanoate Synthase (BioF), Utilizes Different Acyl Chain Donors in Bacillus subtilis and Escherichia coli. Appl Environ Microbiol 84:
Cao, Xinyun; Zhu, Lei; Song, Xuejiao et al. (2018) Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes. Proc Natl Acad Sci U S A 115:E7063-E7072
Srinivas, Swaminath; Cronan, John E (2017) An Eight-Residue Deletion in Escherichia coli FabG Causes Temperature-Sensitive Growth and Lipid Synthesis Plus Resistance to the Calmodulin Inhibitor Trifluoperazine. J Bacteriol 199:
Manandhar, Miglena; Cronan, John E (2017) Pimelic acid, the first precursor of the Bacillus subtilis biotin synthesis pathway, exists as the free acid and is assembled by fatty acid synthesis. Mol Microbiol 104:595-607
Cao, Xinyun; Zhu, Lei; Hu, Zhe et al. (2017) Expression and Activity of the BioH Esterase of Biotin Synthesis is Independent of Genome Context. Sci Rep 7:2141
Bi, Hongkai; Zhu, Lei; Jia, Jia et al. (2016) A Biotin Biosynthesis Gene Restricted to Helicobacter. Sci Rep 6:21162
Henke, Sarah K; Cronan, John E (2016) The Staphylococcus aureus group II biotin protein ligase BirA is an effective regulator of biotin operon transcription and requires the DNA binding domain for full enzymatic activity. Mol Microbiol 102:417-429
Cronan, John E (2016) pBR322 vectors having tetracycline-dependent replication. Plasmid 84-85:20-6
Bi, Hongkai; Zhu, Lei; Jia, Jia et al. (2016) Unsaturated Fatty Acid Synthesis in the Gastric Pathogen Helicobacter pylori Proceeds via a Backtracking Mechanism. Cell Chem Biol 23:1480-1489

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