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We previously identified the aur1 gene cluster which produces the angucycline antibiotic auricin. Preliminary characterisation of auricin revealed that it is modified by a single aminodeoxysugar, D-forosamine. Here we characterise the D-forosamine-specific genes. The four close tandem genes, aur1TQSV, encoding enzymes involved in the initial steps of the deoxysugar biosynthesis, were located on a large operon with other core auricin biosynthetic genes. Deleting these genes resulted in the absence of auricin and the production of deglycosylated auricin intermediates. The two final D-forosamine biosynthetic genes, sa59, an NDP-hexose aminotransferase, and sa52, an NDP-aminohexose N-dimethyltransferase, are located in a region rather distant from the core auricin genes. A deletion analysis of these genes confirmed their role in D-forosamine biosynthesis. The Δsa59 mutant had a phenotype similar to that of the cluster deletion mutant, while the Δsa52 mutant produced an auricin with a demethylated D-forosamine. Although auricin contains a single deoxyhexose, two glycosyltransferase genes were found to participate in the attachment of D-forosamine to the auricin aglycon. An analysis of the expression of the D-forosamine biosynthesis genes revealed that the initial D-forosamine biosynthetic genes aur1TQSV are regulated together with the other auricin core genes by the aur1Ap promoter under the control of the auricin-specific activator Aur1P. The expression of the other D-forosamine genes, however, is governed by promoters differentially dependent upon the two SARP family auricin-specific activators Aur1PR3 and Aur1PR4. These promoters contain direct repeats similar to the SARP consensus sequence and are involved in the interaction with both regulators.

A series of 1-glycosylmethyl-4,5-diphenyl-1H-imidazoles with six different glycosyls were obtained in 48-55% yields from the multicomponent reaction of the corresponding C-glycosyl methylamines, formaldehyde, benzil, and ammonium acetate under catalysis with indium(III) chloride in methanol at ambient temperature. Starting with C--D-glucopyranosyl or C--Dgalactopyranosyl methylamines, the procedure also was examined with phenylglyoxal or glyoxal instead of benzil, and the pertinent 1--D-glycopyranosylmethyl-4-phenyl-1Himidazole and -5-phenyl-1H-imidazole or 1--D-glycopyranosylmethyl-1H-imidazole derivatives were prepared and isolated. Of four differently 4-and 5-substituted 1-(-Dglucopyranosylmethyl)-1H-imidazoles, only the 5-phenyl derivative exhibited a weak inhibition of rabbit muscle glycogen phosphorylase b (IC 50 = 125 μM).