Elucidation of Oxygenation Steps during Oviedomycin Biosynthesis and Generation of Derivatives with Increased Antitumor Activity

作者：Lombo Felipe; Abdelfattah Mohamed S; Brana Alfredo F; Salas Jose A; Rohr Juergen^*; Mendez Carmen

来源：ChemBioChem, 2009, 10(2): 296-303.

DOI：10.1002/cbic.200800425

• angucycline
• antitumor agents
• combinatorial biosynthesis
• polyketides
• Streptomyces

Eight different angucyclinones have been produced in Streptomyces albus by combining three oxygenase genes together with the polyketide synthase and cycloses genes from the oviedomycin biosynthetic gene cluster from Streptomyces antibioticus ATCC 11891. Four of these compounds were fully characterized for the first time. Three of these angucyclinones-prejadomycin-2-carboxylate (2), 4a, 12b-dehydro-UWM6 (5), and prejadomycin (3)show a significant increase in their in vitro antitumor activity relative to oviedomycin (1). A hypothesis for the sequence of tailoring events catalyzed by these three oxygenases during oviedomycin biosynthesis is proposed. In this hypothesis OvmOll acts as a bifunctional oxygenase/dehydratase.

• 出版日期2009-1-26