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Systematic Engineering to Enhance 8-Hydroxygeraniol Production in Yeast. | LitMetric

Systematic Engineering to Enhance 8-Hydroxygeraniol Production in Yeast.

J Agric Food Chem

Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.

Published: March 2023

AI Article Synopsis

  • 8-Hydroxygeraniol is a key compound in insect pheromones and has potential as a natural insect repellent in agriculture, with microbial production offering a sustainable method for its synthesis.
  • The study focused on improving the efficiency of converting geraniol to 8-hydroxygeraniol by addressing limitations in the P450 enzyme involved and optimizing the associated cellular systems.
  • The researchers successfully increased production levels significantly, achieving the highest reported titer of 8-hydroxygeraniol in microbes through advanced fermentation techniques, showcasing a promising approach for bioengineering in this field.

Article Abstract

8-Hydroxygeraniol, an important component of insect sex pheromones and defensive secretions, can be used as a potential biological insect repellent in agriculture. Microbial production provides sustainable and green means to efficiently gain 8-hydroxygeraniol. The conversion of geraniol to 8-hydroxygeraniol by P450 geraniol-8-hydroxylase (G8H) was regarded as the bottleneck for 8-hydroxygeraniol production. Herein, an integrated strategy consisting of the fitness between G8H and cytochrome P450 reductase (CPR), endoplasmic reticulum (ER) engineering, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) supply is implemented to enhance the production of 8-hydroxygeraniol in . The titer of 8-hydroxygeraniol was gradually increased by 2.1-fold (up to 158.1 mg/L). Moreover, dehydrogenase and reductase responsible for the reduction of 8-hydroxygeraniol toward shunt products were also deleted, elevating 8-hydroxygeraniol production to 238.9 mg/L at the shake flask level. Consequently, more than 1.0 g/L 8-hydroxygeraniol in was achieved in 5.0 L fed-batch fermentation by a carbon restriction strategy, which was the highest-reported titer in microbes so far. Our work not only provides a sustainable way for biosynthesis of 8-hydroxygeraniol but also sets a good reference in P450 engineering in microbes.

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Source
http://dx.doi.org/10.1021/acs.jafc.2c09028DOI Listing

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