Synthesis and biological evaluation of a bicyclo[4.1.0]heptyl analogue of glucose-1-phosphate

The synthesis of a bicyclo[4.1.0]heptyl analogue of glucose-1-phophate, (1R,2R,3S,4S,5S,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)-bicyclo[4.1.0]heptan-2-yl dihydrogen phosphate (5) is reported. The synthetic route chosen started with methyl α-D-glucopyranoside and was accomplished in 11 steps with an overall yield of 3%. Compound 5 was tested as a potential substrate of UTP:α-D-glucose-1-phosphate uridylyltransferase, the enzyme that converts glucose-1-phosphate into UDP-glucose. However, the conformationally restricted glucose-1-phosphate analogue 5 was found to be a weakly binding inhibitor, rather than a substrate, of the yeast transferase (12% inhibition at a concentration of 0.1 mmol L–1).Key words: glucose 1-phosphate, inhibition, UTP:α-D-glucose-1-phosphate uridylyltransferase.

Production of β-glucosidase and diauxic usage of sugar mixtures byCandida molischiana

The fermentation of cellobiose is a rare trait among yeasts. Of the 308 yeast species that utilize cellobiose aerobically, only 12 species ferment it, and only 2 species, Candida molischiana and Candida wickerhamii, also ferment cellodextrins. Candida molischiana produced β-glucosidase activity on all carbon sources tested, except glucose, mannose, and fructose. When these sugars were added to cultures growing on cellobiose, the synthesis of β-glucosidase ceased. However, the total amount of enzyme activity remained constant, indicating that the C. molischiana β-glucosidase is catabolite repressed and not catabolite inactivated. When grown in medium initially containing glucose plus xylose, cellobiose, maltose, mannitol, or glucitol, C. molischiana preferentially utilized glucose and produced little β-glucosidase activity until glucose was nearly depleted from the medium. When grown in medium containing cellobiose plus either fructose or mannose, the yeast preferentially utilized the monosaccharides and produced little β-glucosidase activity. Candida molischiana produced β-glucosidase and co-utilized cellobiose and xylose, maltose, or trehalose. Glucose and fructose, mannose, or trehalose were co-utilized; however, no β-glucosidase activity was detected. Thus, the order of substrate preference groups appeared to be (glucose, trehalose, fructose, mannose) > (cellobiose, maltose, xylose) > (mannitol, glucitol).Key words: glucose repression, trehalase, diauxic utilization, yeast.