Elucidating alkaloid biosynthesis in Tabernaemontana catharinensis

• Grant number: 19/13153-6
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2020
• End date: August 31, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Adriana Aparecida Lopes
• Grantee: Adriana Aparecida Lopes
• Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil
• Associated researchers: Sarah E O'Connor

Abstract

Plants, microbes and insects produce complex small molecules, called "natural products". Given the energy that the organism must expend to produce these molecules, natural products likely confer an evolutionary advantage for the producing organism. Therefore, most natural products have some type of biological activity. For our purposes, this means that these metabolites are a rich resource for a wide range of applications, including the development of pharmaceuticals, insecticides, herbicides, biomaterials and bioenergy sources. We are especially interested in a class of natural products known as the alkaloids, which are produced by a wide range of plants and insects. One group of alkaloids, called the "monoterpene indole alkaloids" contains a large assortment of alkaloid compounds, where each is produced from the same starting material. The well-known compounds strychnine (a poison), quinine (an anti-malarial), camptothecin (anticancer) and vinblastine (anticancer) are monoterpene indole alkaloids. However, to effectively utilize the compounds that Nature provides, we must develop robust methods for large-scale production of them. Additionally, it would be valuable to have methods to modify the structures of these compounds so we can test additional derivatives for improved biological activity. This means we need to understand the biochemical processes- the biosynthesis- that the plant uses to construct these molecules. Using this knowledge, we can reprogram or genetically engineer plants or microbial organisms to overproduce these valuable compounds. Moreover, if we identify and understand the biocatalysts that the plant uses to synthesize these molecules, we can potentially recombine plant biosynthetic pathways in new ways to make novel molecules with potentially improved biological activities. In this proposal, we describe how we will discover how nature synthesizes some of the monoterpene indole alkaloids. The team is composed of researcher in Brazil who is expert in the natural products chemistry of oxindole alkaloids and the academic partner in the Max Planck Institute is an expert in enzymology and metabolic engineering of monoterpene indole alkaloids. Together, we will identify the genes that are responsible for biosynthesis in two important alkaloids with potent bioactivity from Tabernaemontana catharinensis and use precursor directed biosynthesis to generate analogs of these compounds. (AU)