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Pathway Engineering of Anthracyclines: Blazing Trails in Natural Product Glycodiversification.

ABSTRACT: 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 the generation of "new-to-nature" anthracycline analogues.

SUBMITTER: Brown KV

PROVIDER: S-EPMC7541800 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Pathway Engineering of Anthracyclines: Blazing Trails in Natural Product Glycodiversification.

Brown Katelyn V KV Wandi Benjamin Nji BN Metsä-Ketelä Mikko M Nybo S Eric SE

The Journal of organic chemistry 20200922 19

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 st ...[more]

PMID: 32938175

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