Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 11, Pages 3205-3210Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1423555112
Keywords
monoterpene indole alkaloid; strictosidine; secologanin; Catharanthus roseus; Saccharomyces cerevisiae
Categories
Funding
- Biological Sciences Research Council [BB/J009091/1]
- European Research Council [311363]
- Region Centre [Architecture et Bioingenierie de la synthese d'alcaloides a haute valeur ajoutee (ABISAL) project]
- BBSRC [BB/J009091/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/J009091/1] Funding Source: researchfish
- European Research Council (ERC) [311363] Funding Source: European Research Council (ERC)
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The monoterpene indole alkaloids are a large group of plant-derived specialized metabolites, many of which have valuable pharmaceutical or biological activity. There are similar to 3,000 monoterpene indole alkaloids produced by thousands of plant species in numerous families. The diverse chemical structures found in this metabolite class originate from strictosidine, which is the last common biosynthetic intermediate for all monoterpene indole alkaloid enzymatic pathways. Reconstitution of biosynthetic pathways in a heterologous host is a promising strategy for rapid and inexpensive production of complex molecules that are found in plants. Here, we demonstrate how strictosidine can be produced de novo in a Saccharomyces cerevisiae host from 14 known monoterpene indole alkaloid pathway genes, along with an additional seven genes and three gene deletions that enhance secondary metabolism. This system provides an important resource for developing the production of more complex plant-derived alkaloids, engineering of nonnatural derivatives, identification of bottlenecks in monoterpene indole alkaloid biosynthesis, and discovery of new pathway genes in a convenient yeast host.
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