Heterologous expression and elucidation of the biosynthesis of Rishirilide A and B

J Wunsch-Palasis; X Yan; E Welle; A Bechthold

doi:10.1055/s-0032-1320337

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Planta Med 2012; 78 - PB8
DOI: 10.1055/s-0032-1320337

Heterologous expression and elucidation of the biosynthesis of Rishirilide A and B

J Wunsch-Palasis ¹, X Yan ¹, E Welle ¹, A Bechthold ¹

¹Department of Pharmaceutical Biology and Biotechnology, Albert-Ludwigs-University, Stefan-Meier- st. 19, 79104 Freiburg, Germany

Congress Abstract

Streptomyces bottropensis was found to produce the potent α₂-macroglobulin inhibitors rishirilide A and B 1 by screening the cosmid library for type II PKS genes. After heterologous expression of the rsl-biosynthetic gene cluster 2 in Streptomyces albus rishirilide B could be detected. Inactivation experiments revealed RslO1 catalyzing a Favorskii-like rearrangement during the biosynthesis. Currently feeding experiments with ¹³C-labeled acetates are carried out to support this finding. Furthermore, the results of inactivation experiments of different tailoring oxygenases and the starter unit selection gene rslK4 will be presented.