Engineering <em>Methylobacterium extorquens</em> for de novo synthesis of the sesquiterpenoid alpha-humulene from methanol - Laboratoire des Interactions Plantes Microbes Environnement Accéder directement au contenu
Article Dans Une Revue Metabolic Engineering Année : 2015

Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid alpha-humulene from methanol

Résumé

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. In this study we present de novo synthesis of the sesquiterpenoid alpha-humulene from the abundantly available non-food carbon source methanol by metabolically engineered Methylobacterium extorquens AM1. Expression of alpha-humulene synthase from Zingiber zerumbet in combination with farnesyl pyrophosphate (FPP) synthase from Saccharomyces cerevisiae led to concentrations of up to 18 mg/L alpha-humulene. Introduction of a prokaryotic mevalonate pathway from Myxococcus xanthus in combination with ribosome binding site optimization of alpha-humulene and FPP synthases increased product concentration 3-fold. This value was additionally raised by 30% using a carotenoid synthesis deficient mutant strain. Final product concentrations of up to 1.65 g/L were obtained in methanol limited fed-batch cultivations, which is the highest titer of de novo synthesized alpha-humulene reported to date. This study demonstrates the potential of M. extorquens as a future platform strain for the production of high-value terpenoids from the alternative carbon source methanol. (C) 2015 International Metabolic Engineering Society.
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Dates et versions

hal-02639651 , version 1 (28-05-2020)

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Frank Sonntag, Cora Kroner, Patrice Lubuta, Rémi Peyraud, Angelika Horst, et al.. Engineering Methylobacterium extorquens for de novo synthesis of the sesquiterpenoid alpha-humulene from methanol. Metabolic Engineering, 2015, 32, pp.82-94. ⟨10.1016/j.ymben.2015.09.004⟩. ⟨hal-02639651⟩
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