Biosynthetic Pathway of Macrolactam Polyketide Glycoside Antitumor Antibiotic Vicenistatins

The biosynthetic studies of antitumor antibiotic vicenistatin and vicenistatin M were undertaken by feeding experiments with [1-13C]- and [1,2-13C2]acetate, [1-13C]propionate, dl-[2,3,3-2H3]glutamate, d-[6,6-2H2]glucose, l-[15N]glutamate, and l-[CH3–13C]methionine. The elongating units of the macrolactam aglycon were derived from acetate and propionate in a standard manner, whereas the starter unit was not derived from fatty acid, but rather originated from 3-amino-2-methylpropionate or its equivalent, probably formed by the reactions of glutamate mutase and decarboxylase. The sugar units appeared to be biosynthesized through diversed modification of functional groups of a common intermediate.