title: Bacterial diguanylate cyclases: structure, function and mechanism in exopolysaccharide biofilm development.
abstract: The ubiquitous bacterial cyclic di-guanosine monophosphate (c-di-GMP) emerges as an important messenger for the control of many bacterial cellular functions including virulence, motility, bioluminescence, cellulose biosynthesis, adhesion, secretion, community behaviour, biofilm formation and cell differentiation. The synthesis of this cyclic nucleotide arises from external stimuli on various signalling domains within the N-terminal region of a dimeric diguanylate cyclase. This initiates the condensation of two molecules of guanosine triphosphate juxtaposed to each other within the C-terminal region of the enzyme. The biofilm from pathogenic microbes is highly resistant to antimicrobial agents suggesting that diguanylate cyclase and its product - c-di-GMP - are key biomedical targets for the inhibition of biofilm development. Furthermore the formation and long-term stability of the aerobic granule, a superior biofilm for biological wastewater treatment, can be controlled by stimulation of c-di-GMP. Any modulation of the synthetic pathways for c-di-GMP is clearly advantageous in terms of medical, industrial and/or environmental bioremediation implications. This review discusses the structure and reaction of individual diguanylate cyclase enzymes with a focus on new directions in c-di-GMP research. Specific attention is made on the molecular mechanisms that control bacterial exopolysaccharide biofilm formation and aerobic granules.
authors.affiliation: Graduate Institute of Applied Science & Technology, National Taiwan University of Science and Technology, Taipei, Taiwan. Electronic address: c.whiteley@mail.ntust.edu.tw.
authors.forename: Chris G
authors.initials: CG
authors.lastname: Whiteley
authors.affiliation: Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; Department of Chemical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Duu-Jong
authors.initials: DJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D006152:Cyclic GMP / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000378:metabolism*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011135:Polysaccharides, Bacterial; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP
keywords: Aerobic granules; Bacterial diguanylates cyclase; Biofilm; Biosynthesis; Cyclic di-guanosine monophosphate; Exopolysaccharides; Structure