Abstract:
Taxol (paclitaxel) is a widely used anti-cancer drug with a complex biosynthetic pathway that has puzzled biochemists for decades. Owing to inefficient chemical synthesis, Taxol supply depends on costly semi-synthesis. Elucidating the Taxol biosynthesis will solve a long-standing question in biochemistry and enable cost-effective production using biotechnological methods. While recent advances have improved our understanding of the steps leading up to the intermediate baccatin III, the final steps of the pathway remain elusive. Here we use gene co-expression analysis, chemically synthesized intermediates and a stepwise learning-by-building approach to reveal the enzymes that catalyse the final two modifications, that is, C2′α hydroxylation and 3′-N benzoylation, which are essential for Taxol’s bioactivity. To replace the current semi-synthetic method of Taxol production, we reconstruct the late pathway in yeast and synthesize Taxol from the readily available intermediate baccatin III. This work provides a complete understanding of Taxol biosynthesis and
establishes a foundation for its biotechnological production.

Bio:
Sotirios Kampranis is a Professor of Biochemical Engineering at the University of Copenhagen, Denmark. His work aims to develop biological synthesis as the preferred method for producing complex chemicals, replacing organic synthesis or extraction from plants, which are inefficient and harmful to the environment.

To achieve this goal, his team employs a multidisciplinary approach that combines the discovery of biosynthetic pathways with their reconstruction in engineered microorganisms for the sustainable synthesis of valuable compounds.

His team has pioneered the development of tools and applications in the following areas:
• Elucidation of biosynthetic pathways of plant and microbial specialized metabolites.
• Metabolic engineering of yeast for the bioproduction of high-value compounds.
• Development of protein engineering methods to optimize cell factories.
• Production of novel specialized metabolites by combining protein and metabolic engineering.
• Development of yeast-based whole-cell biosensors for biotechnological applications.

Sotirios is passionate about transforming academic ideas into real-life solutions through their commercialization and the development of industrial products. He is a co-founder and board member of EvodiaBio (www.evodiabio.com), which focuses on the sustainable production of natural fragrances and flavors.