Biosynthetic studies on the alpha-glucosidase inhibitor acarbose in Actinoplanes sp.: source of the maltose unit.

To investigate the source of the maltose unit in acarbose, feeding experiments using 3H- or 2H-labeled maltose or maltotriose were carried out with resting cells of Actinoplanes sp. SN223/29. It was found by experiments with [6"-3H]- and [1-3H]maltotriose that a maltose unit from the nonreducing end of maltotriose is incorporated into acarbose more efficiently than from the reducing end. However, experiments with [6"-2H]- and [2-2H]maltotriose showed that maltose from either the reducing end or from the nonreducing end of maltotriose was incorporated into acarbose. The results established that acarbose is formed from maltotriose by two routes; (1) Sixty percent of the acarbose are formed by attachment of maltose, produced by removing a glucose exclusively from the nonreducing end of maltotriose, to the pseudodisaccharide core unit. (2) The other 40% of the acarbose are formed by direct attachment of maltotriose to the core unit followed by loss of the terminal glucose from the reducing end. Furthermore, it was observed that there is no scrambling of label between the two glucose moieties of acarbose, that maltotriose is a comparably efficient precursor of acarbose as is maltose, and that the core unit is enriched up to 50% from the 2H-glucose liberated from the deuterated maltotrioses.