Oxidative cleavage of premithramycin B is one of the last steps in the biosynthesis of the antitumor drug mithramycin.

Background: Mithramycin is a member of the clinically important aureolic acid group of antitumor drugs that interact with GC-rich regions of DNA nonintercalatively. These drugs contain a chromophore aglycon that is derived from condensation of ten acetate units (catalyzed by a type II polyketide synthase). The aglycones are glycosylated at two positions with different chain length deoxyoligosaccharides, which are essential for the antitumor activity.

Genetic manipulation of antitumor-agent biosynthesis to produce novel drugs.

Current methods of obtaining novel drugs may be complemented in the near future by the genetic engineering of antitumor-agent biosynthesis in microorganisms. Biosynthetic gene clusters from several antitumor pathways in actinomycetes are presently being characterized and expressed in order to generate novel drugs. Several novel hydroxylated and glycosylated antitumor-drug derivatives have been produced that show a relaxed substrate specificity for secondary-metabolic enzymes, which opens up the possibility of generating novel drugs by genetic manipulation.

Two glycosyltransferases and a glycosidase are involved in oleandomycin modification during its biosynthesis by Streptomyces antibioticus.

A 5.2 kb region from the oleandomycin gene cluster in Streptomyces antibioticus located between the oleandomycin polyketide synthase gene and sugar biosynthetic genes was cloned. Sequence analysis revealed the presence of three open reading frames (designated oleI, oleN2 and oleR).