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Scientists Pin Down Quinine’s Biosynthetic Pathway, Paving the Way for Engineered Production

A Max Planck team presents enzyme-by-enzyme validation in Nature.

Overview

  • Researchers in Jena identified three previously unknown intermediates, including malonyl-corynantheol and cinchonium.
  • The team assigned key steps to specific enzymes, naming an oxoglutarate-dependent dioxygenase, a cytochrome P450, and an unexpected transferase that catalyzes a cyclization.
  • Isotope tracing with labeled precursors, comparative gene and protein data, and targeted gene silencing established the sequence of reactions.
  • Using the enzymes, the lab produced established Cinchona alkaloids and generated novel derivatives with potential medical value.
  • The authors say the findings enable synthetic-biology routes that could reduce reliance on bark extraction, a market Phys.org reports is worth roughly $2 billion annually.