Cyclic diguanylate

Hickman, J. W., Tifrea, D. F., and Harwood, C. S. (2005) A chemosensory system that regulates biofilm formation through modulation of cyclic diguanylate levels. Proc. Natl. Acad. Sci. USA 102, 14422-14427. 

Aloni Y, Delmer D.P., and Benziman M. 1982. Achievement of high rates of in vitro synthesis of 1, 4-beta-D-glucan activation by cooperative interaction of the Acetobacter xylinum enzyme system with GTP, polyethylene glycol, and a protein factor. Proc Natl Acad Sci USA 79(21) 6448-6452. Amikam D. and Benziman M. 1989. Cyclic diguanylic acid and cellulose synthesis in Agrobacterium tumefaciens. J Bacterid 171(12) 6649-6655. 

Mayer R., Ross P., Weinhouse H., Amikam D., Vohnan G., Ghana P., Calhoon R.D., Wong H.C., Emerick A.W., and Benziman M. 1991. Polypeptide composition of bacterial cyclic diguanylic acid-dependent cellulose synthase and the occurrence of immunologically crossreacting proteins in higher plants. Proc Natl Acad Sci USA 88(12) 5472-5476. 

Ross R., Weinhouse H., Aloni Y, Michael D., Weinberger-Ohana P., Mayer R., Braun S., de Vroom E., van der Marel G.A., van Boom J.H., and Benziman M. 1987. Regulation of cellulose synthesis in Acetobacter xylinus by cyclic diguanylic acid. Nature 325 279-281. 

Tamayo R, Pratt JT, Camilli A (2007) Roles of cyclic diguanylate in the regulation of bacterial pathogenesis. Annu Rev Microbiol 61 131-148... 

Current enzymatic syntheses of the widespread bacterial messenger molecule cyclic dinucleotide c-di-GMP (70) suffer from low production yields due to protein instability and strong product inhibition. Liang reported the overexpression of a standalone thermophilic diguanylate cyclase domain protein with enhance stability and decreased product inhibition profile due to site-specific mutation. " With this mutant, Liang produced hundreds of milligrams of c-di-GMP. 

In the cellulose-producing bacterium Acetobacter xylinum, the phosphodiesterase A1 protein (AxPDEAl) functions to hydrolyze a potent allosteric activator of the bacterial cellulose synthase, the cyclic nucleotide [cyclic bis(3 —> 5 )diguanylic acid, or c-di-GMP] (17). xPDEAl was recently shown to contain an N-terminal regulatory heme-PAS domain that, when bound to O2, inhibits the C-terminal phosphodiesterase activity (10). Thus in cultures of this obligate aerobe, O2 is now thought to enhance the construction of a buoyant cellulose pellicle by the cells nearest to the media surface for possible use as a biofilm. The type of phosphodiesterase domain found in AxPDEAl, though not extensively studied, is widespread in Bacteria. 

A. xylinum developed faster in black tea infusion than did A. aceti. Cell mass synthesized by A. aceti and A. xylinum increased with incubation time, up to 5 mg % and 22 mg %, respectively, after 25 days as shown in Figure 2. As shown by scaiming electron microscope. Figure 2 shows that some rod-shape A. xylinum cells adhered on the surface of the bacterial cellulose fibrils. Caffeine and theophylline were identified as potent stimulators for bacterial cellulose synthesis in A. xylinum. Methylxanthine probably blocks the action of the specific diguanyl cyclic phosphodiesterase and then avoids or postpones the normal switch off of active cellulose synthase 12). The level of caffeine in the black infusion used in this experiment was determined to be in the range of 2.4 to 3.4 %. This may account for the accumulation of more cell mass in the medium inoculated with A. xylinum rather than in the one with A. aceti. 

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