Li, Yanran and Smolke, Christina (2016) Elucidating and Engineering the Biosynthesis of Noscapine in Saccharomyces cerevisiae. Nature Communications, 7 (N/A). p. 12137. ISSN 2041-1723

Abstract

We describe the full elucidation of the noscapine biosynthetic pathway through a step- wise reconstitution of the proposed gene cluster in S. cerevisiae. Our work offers novel insight into several of the enzymatic steps in this pathway, including the first description of a natural O- methylation step that is catalyzed by a heterodimer. We constructed a yeast strain capable of synthesizing noscapine from the early benzylisoquinoline alkaloid norlaudanosoline, representing the most complex plant pathway reconstructed in a microbial host to date with 15 heterologous enzymes. The engineered yeast strains provide a source for previously inaccessible and novel noscapinoids, thereby advancing new approaches to drug discovery. Our synthetic biology-based approach offers several advantages over traditional elucidation strategies, including characterization in a clean host background, direct supply of pathway intermediates to support structural validation, and simultaneous development of scalable synthesis platforms for accessing pathway intermediates and novel compound derivatives.

Item Type:	Article
Date Deposited:	12 Oct 2016 00:45
Last Modified:	12 Oct 2016 00:45
URI:	https://oak.novartis.com/id/eprint/25097