Refactoring Ehrlich Pathway for High-Yield 2-Phenylethanol Production in Yarrowia lipolytica.

ACS Synthetic Biology
Yang GuPeng Xu

Abstract

Efficient microbial synthesis of chemicals requires the coordinated supply of precursors and cofactors to maintain cell growth and product formation. Substrates with different entry points into the metabolic network have different energetic and redox statuses. Generally, substrate cofeeding could bypass the lengthy and highly regulated native metabolism and facilitates high carbon conversion rate. Aiming to efficiently synthesize the high-value rose-smell 2-phenylethanol (2-PE) in Y. lipolytica, we analyzed the stoichiometric constraints of the Ehrlich pathway and identified that the selectivity of the Ehrlich pathway and the availability of 2-oxoglutarate are the rate-limiting factors. Stepwise refactoring of the Ehrlich pathway led us to identify the optimal catalytic modules consisting of l-phenylalanine permease, ketoacid aminotransferase, phenylpyruvate decarboxylase, phenylacetaldehyde reductase, and alcohol dehydrogenase. On the other hand, mitochondrial compartmentalization of 2-oxoglutarate inherently creates a bottleneck for efficient assimilation of l-phenylalanine, which limits 2-PE production. To improve 2-oxoglutarate (aKG) trafficking across the mitochondria membrane, we constructed a cytosolic aKG source pathway...Continue Reading

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Citations

Jan 14, 2021·Microbial Biotechnology·Macarena LarroudeTristan Rossignol
Mar 3, 2021·Applied Microbiology and Biotechnology·Qiwen MoJifeng Yuan
Oct 22, 2020·Metabolic Engineering Communications·Harley EdwardsPeng Xu
Aug 21, 2020·Metabolic Engineering·Javier Sáez-SáezIrina Borodina

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Methods Mentioned

BETA
deamination
gene knockout
PCR

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