The anthracyclines are structurally diverse anticancer natural products
that bind to DNA and poison the topoisomerase II – DNA complex in cancer
cells. Rational modifications in the deoxysugar functionality are
especially advantageous for synthesizing drugs with improved potency.
Combinatorial biosynthesis of glycosyltransferases and deoxysugar
synthesis enzymes is indispensable for the generation of
glycodiversified anthracyclines. This Synopsis considers recent advances
in glycosyltransferase structural biology and site-directed
mutagenesis, pathway engineering, and deoxysugar combinatorial
biosynthesis with a focus on generation of “new-to-nature" anthracycline
analogs.