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Updated: Aug 15, 2025

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products

A Customizable Approach for the Enzymatic Production and Purification of Diterpenoid Natural Products

Published on: October 4, 2019

Engineering a universal and efficient platform for terpenoid synthesis in yeast.

Yongshuo Ma^1,2, Yuexuan Zu¹, Sanwen Huang^2,3

¹Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02142.

Proceedings of the National Academy of Sciences of the United States of America

|December 28, 2022

Summary

Engineered yeast pathways bypass native metabolic competition, significantly boosting production of key terpenoid precursors like isopentenyl diphosphate (IPP) and geranylgeranyl diphosphate (GGPP) for valuable natural products.

Keywords:

flux redirection isopentenol utilization pathway metabolic engineering prenyl phosphates terpenoids

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Area of Science:

Metabolic Engineering
Synthetic Biology
Yeast Biotechnology

Background:

Terpenoid production in yeast is limited by native metabolic pathways, especially sterol biosynthesis.
Engineering alternative pathways can overcome these limitations.

Purpose of the Study:

To develop novel metabolic pathways in yeast for enhanced terpenoid precursor synthesis.
To circumvent native metabolic competition and increase precursor availability.

Main Methods:

Introduction of a two-step isopentenol utilization pathway (IUP) in *Saccharomyces cerevisiae*.
Engineering a synthetic three-step route for geranylgeranyl diphosphate (GGPP) synthesis.
Cofeed strategies with isoprenol and prenol.

Main Results:

The IUP increased isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) pools by 147-fold.
A synthetic route elevated geranylgeranyl diphosphate (GGPP) levels by 374-fold, bypassing sterol competition.
Combined strategies enhanced the production of industrially relevant terpenoids.

Conclusions:

The developed IUP and synthetic routes provide a universal platform for terpenoid synthesis in yeast.
This approach effectively overcomes native metabolic limitations for improved natural product production.