Genetic Approaches to Lipid Metabolism

Summary

Principal Investigator: John E Cronan
Abstract: DESCRIPTION (provided by applicant): The proposed work is to continue studies of lipid metabolism in diverse bacteria some of which are human pathogens. Although many aspects of bacterial lipid metabolism were first worked out in the paradigm Escherichia coli, other bacteria differ from E. coli in various aspects. A focus will be on the last step of the fatty acid elongatin cycle, the enoyl-ACP reductase reaction, which is catalyzed by a set of very diverse proteins. Since fatty acids are an essential component of bacterial membrane lipids, several of these enzymes are the targets of antimicrobials. A second focus will be on the mechanisms of synthesis of unsaturated fatty acids, an essential component of the membrane lipids of most bacteria. A major puzzle is the mechanism of unsaturated fatty acid synthesis in the Clostridia, which include a number of serious human pathogens. Further investigations of the mechanisms of synthesis of the fatty acid-derived vitamins, biotin and lipoic acid, which are essential enzyme cofactors in all three domains of life, are proposed. Prior work provided the E. coli synthetic pathway in E. coli. However, some bacteria make these cofactors but lack one or more of the proteins used by. Current work is focused on the Firmicutes which include the Bacilli, Clostridia, Staphlococci and thus many important pathogens. In the case of lipoic acid synthesis Bacillus subtilis requires four proteins to synthesize this cofactor whereas E. coli required only two proteins. One of the essential proteins is a key subunit of an enzyme of single carbon metabolism and this interplay will be studied. The early part of biotin synthesis in Bacillus subtilis differs greatly from the pathway used by E. coli and this pathway will be dissected. A third pathway to be studied is that found in the a-proteobacteria (e.g., Brucella) which seems a variation of the E. coli pathway. Study of the mechanisms regulating the synthesis of the various biotin and lipoic acid synthetic pathways will also be done. The E. coli and Bacillus subtilis biotn regulatory systems are quite novel and not fully understood. Further study of these regulatory mechanisms is proposed. Finally, a new class of bacterial quorum sensing molecules the Diffusible Signal Factor (DSF) fatty acids were recently discovered. These are cis-2-enoic acids of medium chain length which trigger breakdown of the biofilms formed by diverse bacteria and some fungi. Prior work demonstrated how the Burkholderia cenocepacia DSF is synthesized, but that enzyme is not fully understood or conserved in some other DSF- producing bacteria. Study of these pathways and mechanisms will use a wide array of genetic, biochemical, molecular biological, chemical and structural approaches.
Funding Period: 1979-01-01 - 2018-06-30
more information: NIH RePORT

Top Publications

  1. pmc Xanthomonas campestris RpfB is a fatty Acyl-CoA ligase required to counteract the thioesterase activity of the RpfF diffusible signal factor (DSF) synthase
    Hongkai Bi
    Department of Microbiology, B103 Chemical and Life Sciences Laboratory, University of Illinois, 601 S Goodwin Ave, Urbana, IL, 61801, USA
    Mol Microbiol 93:262-75. 2014
  2. pmc The Burkholderia cenocepacia BDSF quorum sensing fatty acid is synthesized by a bifunctional crotonase homologue having both dehydratase and thioesterase activities
    Hongkai Bi
    Departments of Microbiology Biochemistry, B103 Chemical and Life Sciences Laboratory, University of Illinois, 601 S Goodwin Ave, Urbana, IL 61801, USA
    Mol Microbiol 83:840-55. 2012
  3. pmc Only one of the five Ralstonia solanacearum long-chain 3-ketoacyl-acyl carrier protein synthase homologues functions in fatty acid synthesis
    Juanli Cheng
    College of Life Sciences, South China Agricultural University, Guangzhou, China
    Appl Environ Microbiol 78:1563-73. 2012
  4. pmc Dimerization of the bacterial biotin carboxylase subunit is required for acetyl coenzyme A carboxylase activity in vivo
    Alexander C Smith
    Departments of Microbiology, University of Illinois, Urbana, Illinois, USA
    J Bacteriol 194:72-8. 2012
  5. pmc The Vibrio cholerae fatty acid regulatory protein, FadR, represses transcription of plsB, the gene encoding the first enzyme of membrane phospholipid biosynthesis
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 81:1020-33. 2011
  6. pmc A complex lipoate utilization pathway in Listeria monocytogenes
    Quin H Christensen
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 286:31447-56. 2011
  7. ncbi Closing in on complete pathways of biotin biosynthesis
    Steven Lin
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S Goodwin Ave, Urbana, Illinois 61801, USA
    Mol Biosyst 7:1811-21. 2011
  8. pmc Synthesis of the α,ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway
    John E Cronan
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Curr Opin Chem Biol 15:407-13. 2011
  9. pmc A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis
    Quin H Christensen
    Departments of Microbiology Biochemistry Chemistry Biology Interface Training Program, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 80:350-63. 2011
  10. pmc A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis
    Natalia Martin
    Instituto de Biologia Molecular y Celular de Rosario IBR CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
    Mol Microbiol 80:335-49. 2011

Detail Information

Publications55

  1. pmc Xanthomonas campestris RpfB is a fatty Acyl-CoA ligase required to counteract the thioesterase activity of the RpfF diffusible signal factor (DSF) synthase
    Hongkai Bi
    Department of Microbiology, B103 Chemical and Life Sciences Laboratory, University of Illinois, 601 S Goodwin Ave, Urbana, IL, 61801, USA
    Mol Microbiol 93:262-75. 2014
    ....
  2. pmc The Burkholderia cenocepacia BDSF quorum sensing fatty acid is synthesized by a bifunctional crotonase homologue having both dehydratase and thioesterase activities
    Hongkai Bi
    Departments of Microbiology Biochemistry, B103 Chemical and Life Sciences Laboratory, University of Illinois, 601 S Goodwin Ave, Urbana, IL 61801, USA
    Mol Microbiol 83:840-55. 2012
    ..Both activities required the same set of active-site residues. Although dehydratase and thioesterase activities are known activities of the crotonase superfamily, Bcam0581 is the first protein shown to have both activities...
  3. pmc Only one of the five Ralstonia solanacearum long-chain 3-ketoacyl-acyl carrier protein synthase homologues functions in fatty acid synthesis
    Juanli Cheng
    College of Life Sciences, South China Agricultural University, Guangzhou, China
    Appl Environ Microbiol 78:1563-73. 2012
    ..solanacearum fatty acid biosynthesis. Moreover, R. solanacearum FabF1 has the activities of both 3-ketoacyl-acyl carrier protein synthase II and 3-ketoacyl-acyl carrier protein synthase I...
  4. pmc Dimerization of the bacterial biotin carboxylase subunit is required for acetyl coenzyme A carboxylase activity in vivo
    Alexander C Smith
    Departments of Microbiology, University of Illinois, Urbana, Illinois, USA
    J Bacteriol 194:72-8. 2012
    ..In contrast, the wild-type protein supports growth at low expression levels. We conclude that BC must be dimeric to fulfill its physiological function...
  5. pmc The Vibrio cholerae fatty acid regulatory protein, FadR, represses transcription of plsB, the gene encoding the first enzyme of membrane phospholipid biosynthesis
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 81:1020-33. 2011
    ..cholerae plsB promoter to lacZ increased two- to threefold upon supplementation of growth media with oleic acid. Therefore, V. cholerae co-ordinates fatty acid metabolism with 1-acyl G3P synthesis...
  6. pmc A complex lipoate utilization pathway in Listeria monocytogenes
    Quin H Christensen
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 286:31447-56. 2011
    ..These data support a model of an expanded, three-enzyme pathway for lipoic acid scavenging that seems widespread in the Firmicutes phylum of bacteria...
  7. ncbi Closing in on complete pathways of biotin biosynthesis
    Steven Lin
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S Goodwin Ave, Urbana, Illinois 61801, USA
    Mol Biosyst 7:1811-21. 2011
    ..The enzymatic mechanisms and biochemical strategies of these pimelate synthesis models will be discussed in this review...
  8. pmc Synthesis of the α,ω-dicarboxylic acid precursor of biotin by the canonical fatty acid biosynthetic pathway
    John E Cronan
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Curr Opin Chem Biol 15:407-13. 2011
    ..A very restricted set of bacteria have a different pathway in which the pimelate moiety is formed by cleavage of fatty acid synthetic intermediates by BioI, a member of the cytochrome P450 family...
  9. pmc A novel amidotransferase required for lipoic acid cofactor assembly in Bacillus subtilis
    Quin H Christensen
    Departments of Microbiology Biochemistry Chemistry Biology Interface Training Program, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 80:350-63. 2011
    ..Thus, these two homologous enzymes have convergent architectures...
  10. pmc A novel two-gene requirement for the octanoyltransfer reaction of Bacillus subtilis lipoic acid biosynthesis
    Natalia Martin
    Instituto de Biologia Molecular y Celular de Rosario IBR CONICET, Facultad de Ciencias Bioquimicas y Farmaceuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina
    Mol Microbiol 80:335-49. 2011
    ..coliΔlipB strain can be complemented with lipM, but not lipL. These data together with those of the companion article provide evidence that LipM and LipL catalyse sequential reactions in a novel pathway for lipoic acid biosynthesis...
  11. pmc Complex binding of the FabR repressor of bacterial unsaturated fatty acid biosynthesis to its cognate promoters
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 80:195-218. 2011
    ..cholerae fabB promoter, although both proteins efficiently bound the V. cholerae fabA promoter. This asymmetry was shown to be due to the lack of a FabR binding site within the V. cholerae fabB promoter region...
  12. pmc Protein-protein interactions in assembly of lipoic acid on the 2-oxoacid dehydrogenases of aerobic metabolism
    Bachar H Hassan
    Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 286:8263-76. 2011
    ..These results indicate that lipoic acid is not only assembled on the dehydrogenase lipoyl domains but that the enzymes that catalyze the assembly are also present "on site."..
  13. pmc The BioC O-methyltransferase catalyzes methyl esterification of malonyl-acyl carrier protein, an essential step in biotin synthesis
    Steven Lin
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 287:37010-20. 2012
    ..BioC was specific for the malonyl moiety and was inhibited by S-adenosyl-L-homocysteine and sinefungin. High level expression of B. cereus BioC in E. coli blocked cell growth and fatty acid synthesis...
  14. pmc Improved plasmid-based system for fully regulated off-to-on gene expression in Escherichia coli: application to production of toxic proteins
    John E Cronan
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Plasmid 69:81-9. 2013
    ..I report that the construction of E. coli strains that eliminate the background of infectious phage and show that the system can be utilized to express proteins by the phage T7 RNA polymerase/pET vector system...
  15. pmc Crosstalk of Escherichia coli FadR with global regulators in expression of fatty acid transport genes
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, Illinois, United States of America
    PLoS ONE 7:e46275. 2012
    ..The physiological relevance of the fadL and fadD transcription data was validated by direct assays of long chain fatty acid transport...
  16. pmc A Francisella virulence factor catalyses an essential reaction of biotin synthesis
    Youjun Feng
    Department of Microbiology, University of Illinois at Urbana Champaign, IL, 61801, USA Institute of Microbiology, College of Life Science, Zhejiang University, Hangzhou, Zhejiang Province, China
    Mol Microbiol 91:300-14. 2014
    ..The biotin synthesis pathway was reconstituted reaction in vitro and the physiological role of BioJ directly assayed. To the best of our knowledge, these data represent further evidence linking biotin synthesis to bacterial virulence. ..
  17. pmc Proofreading of noncognate acyl adenylates by an acyl-coenzyme a ligase
    Miglena Manandhar
    Department of Microbiology, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Chem Biol 20:1441-6. 2013
    ..The noncognate BioW substrate glutaric acid results in hydrolysis of ATP to AMP with formation of only trace amounts of glutaryl-CoA, thereby mimicking pretransfer editing of incorrect aminoacyl-adenylates by aminoacyl-tRNA synthetases. ..
  18. pmc The wing of a winged helix-turn-helix transcription factor organizes the active site of BirA, a bifunctional repressor/ligase
    Vandana Chakravartty
    From the Departments of Microbiology and
    J Biol Chem 288:36029-39. 2013
    ..This is the first evidence that the wing domain of a wHTH protein can play an important role in enzymatic activity. ..
  19. pmc Inefficient translation renders the Enterococcus faecalis fabK enoyl-acyl carrier protein reductase phenotypically cryptic
    Hongkai Bi
    Department of Microbiology, University of Illinois, Urbana, Illinois, USA
    J Bacteriol 196:170-9. 2014
    ....
  20. pmc The two functional enoyl-acyl carrier protein reductases of Enterococcus faecalis do not mediate triclosan resistance
    Lei Zhu
    Guangdong Provincial Key Laboratory of Protein Function and Regulation in Agricultural Organisms, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong, China
    MBio 4:e00613-13. 2013
    ..Strains carrying a deletion of fabK grow normally without fatty acid supplementation, whereas fabI deletion mutants make only traces of fatty acids and are unsaturated fatty acid auxotrophs...
  21. ncbi FabQ, a dual-function dehydratase/isomerase, circumvents the last step of the classical fatty acid synthesis cycle
    Hongkai Bi
    Department of Microbiology, The School of Molecular and Cellular Biology, B103 Chemical and Life Sciences Laboratory, University of Illinois at Urbana Champaign, 601 South Goodwin Avenue, Urbana, IL 61801, USA
    Chem Biol 20:1157-67. 2013
    ..FabQ therefore provides a potential pathway for bacterial synthesis of polyunsaturated fatty acids. ..
  22. pmc The role of the Saccharomyces cerevisiae lipoate protein ligase homologue, Lip3, in lipoic acid synthesis
    Fatemah A Hermes
    Department of Microbiology, University of Illinois, Urbana, IL, USA
    Yeast 30:415-27. 2013
    ..We report that the Lip3 Lpl homologue of the yeast S. cerevisiae has octanoyl-CoA-protein transferase activity, and discuss implications of this activity on the physiological role of Lip3 in lipoate synthesis...
  23. pmc Brucella BioR regulator defines a complex regulatory mechanism for bacterial biotin metabolism
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, Illinois, USA
    J Bacteriol 195:3451-67. 2013
    ..melitensis. Together, we conclude that Brucella BioR is not only a negative autoregulator but also a repressor of expression of bioY and bio operons that separately function in biotin transport and the biosynthesis pathway. ..
  24. pmc Profligate biotin synthesis in α-proteobacteria - a developing or degenerating regulatory system?
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Mol Microbiol 88:77-92. 2013
    ..5% of the total biotin, most of which is found in the culture medium. To the best of our knowledge, A. tumefaciens represents the first example of profligate biotin synthesis by a wild type bacterium...
  25. pmc Remarkable diversity in the enzymes catalyzing the last step in synthesis of the pimelate moiety of biotin
    Madelyn M Shapiro
    Department of Microbiology, University of Illinois, Urbana, Illinois, United States of America
    PLoS ONE 7:e49440. 2012
    ..A postulated BioG-BioC fusion protein was shown to functionally replace both the BioH and BioC functions of E. coli. Although the BioH, BioG and BioK esterases catalyze a common reaction, the proteins are evolutionarily distinct...
  26. pmc Structure of the enzyme-acyl carrier protein (ACP) substrate gatekeeper complex required for biotin synthesis
    Vinayak Agarwal
    Center for Biophysics and Computational Biology, Institute for Genomic Biology, Department of Microbiology and Biochemistry, University of Illinois, Urbana, IL 61801, USA
    Proc Natl Acad Sci U S A 109:17406-11. 2012
    ..We report the 2.05-Å resolution cocrystal structure of a complex of BioH with pimeloyl-ACP methyl ester and use the structure to demonstrate that BioH is the gatekeeper and its physiological substrate is pimeloyl-ACP methyl ester...
  27. pmc Lipoic acid synthesis: a new family of octanoyltransferases generally annotated as lipoate protein ligases
    Quin H Christensen
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, United States
    Biochemistry 49:10024-36. 2010
    ..LipM type octanoyltransferases represent a new clade of the PF03099 protein family, suggesting that octanoyl transfer activity has evolved at least twice within this superfamily...
  28. pmc Biotin synthesis begins by hijacking the fatty acid synthetic pathway
    Steven Lin
    Department of Microbiology, University of Illinois, Urbana, Illinois, USA
    Nat Chem Biol 6:682-8. 2010
    ....
  29. pmc Overlapping repressor binding sites result in additive regulation of Escherichia coli FadH by FadR and ArcA
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Bacteriol 192:4289-99. 2010
    ..In the absence of the CRP-cAMP complex, repression of fadH expression by both FadR and ArcA-ArcB was very weak, suggesting a possible interplay with other DNA binding proteins...
  30. ncbi In vivo resolution of conflicting in vitro results: synthesis of biotin from dethiobiotin does not require pyridoxal phosphate
    Ahmed M Abdel-Hamid
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Chem Biol 14:1215-20. 2007
    ..The BioB-dependent conversion of dethiobiotin to biotin proceeded in these cells irrespective of the presence or absence of PLP...
  31. pmc Dephospho-CoA kinase provides a rapid and sensitive radiochemical assay for coenzyme A and its thioesters
    Caryn Wadler
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Anal Biochem 368:17-23. 2007
    ..Due to the enzymatic radiophosphorylation, the assay is specific for CoA and its short chain thioesters and is sensitive to sub-picomole levels of these compounds...
  32. ncbi In vivo functional analyses of the type II acyl carrier proteins of fatty acid biosynthesis
    Nicholas R De Lay
    Department of Microbiology, University of Illinois at Urbana Champaign, 601 S Goodwin Avenue, Urbana, IL 61801, USA
    J Biol Chem 282:20319-28. 2007
    ..The fact that an ACP from a such diverse organism can replace AcpP function in E. coli suggests that some of the protein-protein interactions detected for AcpP may be not be essential for growth of E. coli...
  33. ncbi Acyl carrier protein phosphodiesterase (AcpH) of Escherichia coli is a non-canonical member of the HD phosphatase/phosphodiesterase family
    Jacob Thomas
    Department of Microbiology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Biochemistry 46:129-36. 2007
    ..We conclude that AcpH is a member of the HD protein family despite the lack of the signature histidine residue...
  34. pmc Coordinate expression of the acetyl coenzyme A carboxylase genes, accB and accC, is necessary for normal regulation of biotin synthesis in Escherichia coli
    Ahmed M Abdel-Hamid
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    J Bacteriol 189:369-76. 2007
    ..The observed disruption of biotin synthesis and attachment provides an excellent rationale for the observation that in the vast majority of sequenced bacterial genomes AccB and AccC are encoded in a two-gene operon...
  35. ncbi Avant garde fatty acid synthesis by trypanosomes
    John E Cronan
    Department of Microbiology, University of Illinois, Urbana, 61801, USA
    Cell 126:641-3. 2006
    ..This is an unexpected finding as these enzymes were thought only to elongate already long (C16 or C18) acyl chains...
  36. ncbi The soluble acyl-acyl carrier protein synthetase of Vibrio harveyi B392 is a member of the medium chain acyl-CoA synthetase family
    Yanfang Jiang
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    Biochemistry 45:10008-19. 2006
    ..These data indicate that AasS is responsible for a high-affinity and high-capacity uptake system that efficiently converts exogenous fatty acids into acyl-ACP species competent to enter the fatty acid biosynthetic cycle...
  37. ncbi A genome rearrangement has orphaned the Escherichia coli K-12 AcpT phosphopantetheinyl transferase from its cognate Escherichia coli O157:H7 substrates
    Nicholas R De Lay
    Department of Microbiology, University of Illinois, Urbana, IL, 61801, USA
    Mol Microbiol 61:232-42. 2006
    ..We also show that the previously reported suppression of an acpS mutation by the deletion of Lon protease is an artifact of the increased capsular polysaccharide production of lon strains...
  38. pmc The Mycobacterium tuberculosis LipB enzyme functions as a cysteine/lysine dyad acyltransferase
    Qingjun Ma
    EMBL Hamburg Unit, European Molecular Biology Laboratory, Notkestrasse 85, 22603 Hamburg, Germany
    Proc Natl Acad Sci U S A 103:8662-7. 2006
    ....
  39. pmc The beta-oxidation systems of Escherichia coli and Salmonella enterica are not functionally equivalent
    Surtaj Hussain Iram
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S Goodwin Ave, Urbana, IL 61801, USA
    J Bacteriol 188:599-608. 2006
    ..Exchange of homologous genes between the two organisms showed that the S. enterica FadE and FadBA enzymes were responsible for the greater efficiency of beta-oxidation relative to that of E. coli...
  40. pmc Gene-specific random mutagenesis of Escherichia coli in vivo: isolation of temperature-sensitive mutations in the acyl carrier protein of fatty acid synthesis
    Nicholas R De Lay
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S Goodwin Avenue, Urbana, IL 61801, USA
    J Bacteriol 188:287-96. 2006
    ..Fatty acid synthesis in strains that carried the D38V or A68T/N73D mutations was inhibited upon a shift to the nonpermissive temperature and in the latter case declined to a small percentage of the rate of the wild-type strain...
  41. pmc The Lactococcus lactis FabF fatty acid synthetic enzyme can functionally replace both the FabB and FabF proteins of Escherichia coli and the FabH protein of Lactococcus lactis
    Rachael M Morgan-Kiss
    Department of Microbiology, B103 Chemical and Life Sciences Laboratory, University of Illinois at Urbana Champaign, 601 S Goodwin Ave, Urbana, IL 61801, USA
    Arch Microbiol 190:427-37. 2008
    ..Incorporation of octanoate and decanoate labeled with deuterium showed that these acids were incorporated intact as the distal methyl and methylene groups of the long chain fatty acids...
  42. pmc Mechanism of a prototypical synthetic membrane-active antimicrobial: Efficient hole-punching via interaction with negative intrinsic curvature lipids
    Lihua Yang
    Department of Materials Science and Engineering, University of Illinois at Urbana Champaign, Urbana, IL 61801, USA
    Proc Natl Acad Sci U S A 105:20595-600. 2008
    ..By comparing to exactly solvable 1D spin models for magnetic systems, we quantify the cooperativity of these antimicrobials...
  43. pmc Diversity in enoyl-acyl carrier protein reductases
    R P Massengo-Tiassé
    Department of Microbiology, Chemical and Life Sciences Laboratory, University of Illinois at Urbana Champaign, 601 S Goodwin Ave, Urbana, IL 61801, USA
    Cell Mol Life Sci 66:1507-17. 2009
    ..In this review, we discuss the diversity of ENRs, and their inhibitors in the light of current research progress...
  44. pmc The switch regulating transcription of the Escherichia coli biotin operon does not require extensive protein-protein interactions
    José Solbiati
    Department of Microbiology, University of Illinois, Urbana, IL 61801, USA
    Chem Biol 17:11-7. 2010
    ....
  45. pmc Transcriptional patterns in both host and bacterium underlie a daily rhythm of anatomical and metabolic change in a beneficial symbiosis
    Andrew M Wier
    Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, WI 53706, USA
    Proc Natl Acad Sci U S A 107:2259-64. 2010
    ..Thus, the persistent maintenance of the squid-vibrio symbiosis is tied to a dynamic diel rhythm that involves both partners...
  46. pmc Intein-mediated cyclization of bacterial acyl carrier protein stabilizes its folded conformation but does not abolish function
    Gerrit Volkmann
    Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada
    J Biol Chem 285:8605-14. 2010
    ..Our results thus suggest that ACP must be able to adopt a folded conformation for biological activity, and that its function does not require complete unfolding of the protein...
  47. pmc Antibacterial activity of N-pentylpantothenamide is due to inhibition of coenzyme a synthesis
    Jacob Thomas
    Departments of Microbiology, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Antimicrob Agents Chemother 54:1374-7. 2010
    ..We report that AcpH readily removes the N5-Pan-modified prosthetic group both in vivo and in vitro and show that N5-Pan blocks coenzyme A synthesis...
  48. pmc Expression of Vibrio harveyi acyl-ACP synthetase allows efficient entry of exogenous fatty acids into the Escherichia coli fatty acid and lipid A synthetic pathways
    Yanfang Jiang
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    Biochemistry 49:718-26. 2010
    ..coli mutant strains that lack essential fatty acid synthesis enzymes. Thus, this strategy provides a new tool for circumventing the loss of enzymes essential for FAS function...
  49. pmc Triclosan resistance of Pseudomonas aeruginosa PAO1 is due to FabV, a triclosan-resistant enoyl-acyl carrier protein reductase
    Lei Zhu
    College of Life Science, Key Laboratory of Animal Disease Control and Prevention of the Ministry of Agriculture of China, South China Agricultural University, Wushan Road, No 483, Tianhe, Guangzhou 510642, People s Republic of China
    Antimicrob Agents Chemother 54:689-98. 2010
    ..Upon deletion of the fabV gene, the mutant strain became extremely sensitive to triclosan (>2,000-fold more sensitive than the wild-type strain), whereas the mutant strain lacking FabI remained completely resistant to the biocide...
  50. pmc Scavenging of cytosolic octanoic acid by mutant LplA lipoate ligases allows growth of Escherichia coli strains lacking the LipB octanoyltransferase of lipoic acid synthesis
    Fatemah A M Hermes
    Department of Microbiology, University of Illinois, 601 S Goodwin Ave, Urbana, IL 61801, USA
    J Bacteriol 191:6796-803. 2009
    ..The LplA proteins encoded by the mutant genes have reduced K(m) values for free octanoic acid and thus are able to scavenge cytosolic octanoic acid for octanoylation of lipoyl domains...
  51. pmc A new member of the Escherichia coli fad regulon: transcriptional regulation of fadM (ybaW)
    Youjun Feng
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S Goodwin Ave, Urbana, IL 61801, USA
    J Bacteriol 191:6320-8. 2009
    ..Although the gene is not essential for growth, the high basal level of fadM expression under diverse growth conditions suggests that the encoded thioesterase has functions in addition to beta-oxidation...
  52. pmc Escherichia coli unsaturated fatty acid synthesis: complex transcription of the fabA gene and in vivo identification of the essential reaction catalyzed by FabB
    Youjun Feng
    Department of Microbiology, University of Illinois, Urbana, Illinois 61801, USA
    J Biol Chem 284:29526-35. 2009
    ..These data indicate that the key reaction in UFA synthesis catalyzed by FabB is elongation of the cis-3-decenoyl-ACP produced by FabA...
  53. pmc The Thermoplasma acidophilum LplA-LplB complex defines a new class of bipartite lipoate-protein ligases
    Quin H Christensen
    Departments of Microbiology, Urbana, Illinois 61801, USA
    J Biol Chem 284:21317-26. 2009
    ..We propose that the presence of an accessory domain provides a diagnostic to distinguish lipoyl ligase homologues from other members of the lipoate/biotin attachment enzyme family...
  54. pmc Functions of the Clostridium acetobutylicium FabF and FabZ proteins in unsaturated fatty acid biosynthesis
    Lei Zhu
    College of Life Science, South China Agricultural University, Guangzhou 510642, PR China
    BMC Microbiol 9:119. 2009
    ..acetobutylicium, FabZ and FabF might also function in the unsaturated arm of the pathway (a FabZ homologue is known to be an unsaturated fatty acid synthetic enzyme in enterococci)...
  55. ncbi A family of arabinose-inducible Escherichia coli expression vectors having pBR322 copy control
    John E Cronan
    Department of Microbiology, University of Illinois, B103 Chemical and Life Sciences Laboratory, 601 S Goodwin Ave, Urbana, IL 61801, USA
    Plasmid 55:152-7. 2006
    ....

Research Grants30

  1. REGULATION OF LIPID METABOLISM IN BACTERIA
    Charles O Rock; Fiscal Year: 2013
    ..This research will provide a definitive answer regarding the suitability of membrane lipid synthesis in Gram-positive pathogens as a target for novel antibacterial drug discovery development. ..
  2. Regulation of Bacteroides fragilis multidrug efflux pumps
    Hannah Wexler; Fiscal Year: 2013
    ..Bacteroides fragilis is an important member of the gut microbiota that has critical roles in human health and disease. We have virtually no information about these pumps or their regulation in this important anaerobic pathogen. ..
  3. Chemistry and Biology of Bacterial Sulfonucleotide Reductases
    KATE SUZANNE CARROLL; Fiscal Year: 2013
    ..Furthermore, we anticipate that these experiments will lead to important new fundamental insights into the (bio)chemistry of protein-associated iron-sulfur clusters and bacterial sulfur metabolism. ..
  4. Site-specific protein labeling in cells with engineered LplA
    Alice Y Ting; Fiscal Year: 2013
    ....
  5. Membrane-associated Steps in Coenzyme B12 Biosynthesis
    Norbert K Tavares; Fiscal Year: 2013
    ....
  6. Structure-function analyses of siderophore biosynthetic enzymes
    Audrey L Lamb; Fiscal Year: 2013
    ..The goal of this work is to provide a fundamental understanding of four enzymes that promote virulence in P. aeruginosa so that this information can be exploited to generate new antimicrobial drugs. ..
  7. Pacific NorthWest Regional Center of Excellence (PNWRCE)
    Jay A Nelson; Fiscal Year: 2013
    ..pseudomallei host pathogen response during both the septicemic as well as the intracellular phases of the disease. ..
  8. Biosynthesis of Microbial Isoprenoids
    David E Cane; Fiscal Year: 2013
    ....
  9. The Electricidal Effect, a Novel Anti-Biofilm Strategy
    Robin Patel; Fiscal Year: 2013
    ..This new strategy would overcome the resistance to traditional antibiotics of microorganisms in biofilms. ..
  10. Discovery, Design, and Development of Phosphonic Acid Antibiotics
    William W Metcalf; Fiscal Year: 2013
    ..The entire project will be housed in the new Institute for Genomic Biology at the University of Illinois, where the program project team occupies a single, large contiguous, laboratory. ..
  11. Studies of Isoprenoid Biosynthesis
    CHARLES DALE POULTER; Fiscal Year: 2013
    ....
  12. Rocky Mountain Regional Center of Excellence or Biodefense and Emerging Infectiou
    John T Belisle; Fiscal Year: 2013
    ..abstract_text> ..
  13. Mechanism of cellulose synthesis and transport across biological membranes
    Jochen Zimmer; Fiscal Year: 2013
    ..Overall, we undertake a multi-disciplinary approach to reveal how one of nature's most abundant polymers is synthesized and translocated across biological membranes. ..