Acarbose (1) is an oral a-glucosidase inhibitor and clinically useful drug for the treatment of type II insulin-independent diabetes isolated from Actinoplanes sp.. Validamycin A (2) is an antibiotic isolated from Streptomyces hygrocopicus var. limoneus. These are two examples of pseudosaccharide containing cyclitol moieties, a so-called mC₇N unit. Feeding experiments with [U-¹³C₃]glycerol to the acarbose producer Actinoplanes sp. and with [U-¹³C₆]glucose to the validamycins producer S. hygrocopicus, revealed coupling and labelling patterns which were incompatible with a shikimate pathway origin of the C₇N unit, in these compounds. The productions of acarbose and validamycins are strongly dependent upon the fermentation conditions, which drew the necessity of knowledge of the biosynthetic pathway of these drugs in order to improve the efficiency of their commercial productions.

For many years, our group has been working on the biosynthetic pathway of acarbose and validamycin A via conventional methods as well as via genetic approaches. Recently, we have successfully figured out the key intermediates of the cyclitol moieties in both acarbose and the validamycins. The cyclization mechanism from a heptulose 7-phosphate to a cyclitol as the precursor of acarbose and validamycins is also established in a collaboration with Prof. Piepersberg’s group at University of Wuppertal.