Engineering Methylobacterium extorquens for production of the sesquiterpenoid α-humulene

Bild Forschungsprojekt
Period: 01.01.2012 - 31.12.2014       
Partner: ETH Zürich, Stiftelsen SINTEF, Rijksuniversiteit Groningen (RUG), PROMAR AS, Universität Bielefeld, INSA Toulouse, Insilico Biotechnology AG
Funder: EU
Project Manager: Dr. Markus Buchhaupt
Research Group: Biochemical Engineering

Over the last 10 to 15 years, metabolic engineering of microbes has become a versatile tool for high-level de novo synthesis of terpenoids, with the sesquiterpenoids armopha-1,4-diene, farnesene and artemisinic acid as prime examples. However, almost all cell factory approaches towards terpenoids to date have been based on sugar as the raw material, which is mainly used as a food resource and subject to high price volatilities.

This project focuses on the de novo synthesis of the sesquiterpenoid α-humulene from the abundantly available non-food carbon source methanol by metabolically engineered Methylobacterium extorquens. We want to make use of the intermediate acetoacetyl-CoA, which is part of the central metabolism of the organism but also the starting metabolite of the terpene-producing mevalonate pathway. Expression of this pathway together with prenyltransferase and a plant α-humulene synthase resulted in production of this model terpenoid. The use of a tightly controlled expression system and fine tuning of the translation rates of specific mRNAs allowed the production of 1.6g/L humulene in a bioreactor.

This project demonstrates the potential of M. extorquens as a future platform strain for the production of high-value terpenoids from the alternative carbon source methanol.

 

 

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Tel.: +49 69 / 75 64-629

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