Aranciamycin analogs generated by combinatorial biosynthesis show improved antitumor activity.

Andriy Luzhetskyy, Jens Hoffmann, Stefan Pelzer, Sven-Eric Wohlert, Andreas Vente, Andreas Bechthold
Author Information
  1. Andriy Luzhetskyy: Albert-Ludwigs-Universität, Institut für Pharmazeutische Wissenschaften, Stefan-Meier-Strasse 19, Freiburg, Germany.

Abstract

Expression of the aranciamycin biosynthetic gene cluster in Streptomyces diastatochromogenes Tü6028 resulted in production of four novel compounds, aranciamycins E, F, G, and H with different decorations in the tetracyclic backbone. Two derivatives contain a D-amicetose moiety at C7 (aranciamycins F and G), two are hydroxylated at position C1 (aranciamycins E and G), and one is hydroxylated at C13 (aranciamycin F). Analysis of the biological activities of the aranciamycins against two human tumor cell lines--MCF-7 and MATU--shows surprising impact of the hydroxyl group at position C1 on activity. As aranciamycins E and G were the most active derivatives, hydroxylation of the C1 appears to coincide with increased antitumor activity of aranciamycins.

MeSH Term

Amino Acid Sequence
Anthracyclines
Antineoplastic Agents
Cell Line, Tumor
Genetic Engineering
Humans
Molecular Sequence Data
Sequence Alignment
Streptomyces
Structure-Activity Relationship

Chemicals

Anthracyclines
Antineoplastic Agents
aranciamycin

Word Cloud

Created with Highcharts 10.0.0aranciamycinsGEFC1activityaranciamycinderivativestwohydroxylatedpositionantitumorExpressionbiosyntheticgeneclusterStreptomycesdiastatochromogenesTü6028resultedproductionfournovelcompoundsHdifferentdecorationstetracyclicbackboneTwocontainD-amicetosemoietyC7oneC13Analysisbiologicalactivitieshumantumorcelllines--MCF-7MATU--showssurprisingimpacthydroxylgroupactivehydroxylationappearscoincideincreasedAranciamycinanalogsgeneratedcombinatorialbiosynthesisshowimproved

Similar Articles

Cited By