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Engineering of l-tyrosine oxidation in Escherichia coli and microbial production of hydroxytyrosol

Paper ID Volume ID Publish Year Pages File Format Full-Text
31711 44832 2012 8 PDF Available
Title
Engineering of l-tyrosine oxidation in Escherichia coli and microbial production of hydroxytyrosol
Abstract

The hydroxylation of tyrosine is an important reaction in the biosynthesis of many natural products. The use of bacteria for this reaction has not been very successful due to either the over-oxidation to ortho-quinone when using tyrosinases from bacteria or plants, or the lack of the native cofactor, tetrahydrobiopterin (BH4), needed for the activity of tyrosine hydroxylases (TH). Here, we demonstrate that an Escherichia coli cofactor, tetrahydromonapterin (MH4), can be used as an alternative cofactor for TH in presence of the BH4 regeneration pathway, and tyrosine hydroxylation is performed without over-oxidation. We used this platform for biosynthesis of one of the most powerful antioxidants, hydroxytyrosol. An endogenous aromatic aldehyde oxidase was identified and knocked out to prevent formation of the side product, and this resulted in nearly exclusive production of hydroxytyrosol in engineered E. coli. Finally, hydroxytyrosol production from a simple sugar as a sole carbon source was demonstrated.

► We report tyrosine hydroxylation in E. coli using mouse tyrosine hydroxylase. ► Tyrosine hydroxylase can be functional in E. coli without its original cofactor. ► A native E. coli cofactor can replace the original cofactor of tyrosine hydroxylase. ► Hydroxytyrosol was synthesized in E. coli from glucose using tyrosine hydroxylase.

Keywords
Tyrosine hydroxylase; Tetrahydrobiopterin; Tetrahydromonapterin; Dopa decarboxylase; Hydroxytyrosol; Microbial production
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Engineering of l-tyrosine oxidation in Escherichia coli and microbial production of hydroxytyrosol
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 14, Issue 6, November 2012, Pages 603–610
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us