Production of tyrosine through phenylalanine hydroxylation bypasses the intrinsic feedback inhibition in Escherichia coli

Short Communication
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Abstract

Tyrosine is a proteinogenic aromatic amino acid that is often used as a supplement of food and animal feed, as well as a (bio-)synthetic precursor to various pharmaceutically or industrially important molecules. Extensive metabolic engineering efforts have been made towards the efficient and cost-effective microbial production of tyrosine. Conventional strategies usually focus on eliminating intrinsic feedback inhibition and redirecting carbon flux into the shikimate pathway. In this study, we found that continuous conversion of phenylalanine into tyrosine by the action of tetrahydromonapterin (MH4)-utilizing phenylalanine 4-hydroxylase (P4H) can bypass the feedback inhibition in Escherichia coli, leading to tyrosine accumulation in the cultures. First, expression of the P4H from Xanthomonas campestris in combination with an MH4 recycling system in wild-type E. coli allowed the strain to accumulate tyrosine at 262 mg/L. On this basis, enhanced expression of the key enzymes associated with the shikimate pathway and the MH4 biosynthetic pathway resulted in the elevation of tyrosine production up to 401 mg/L in shake flasks. This work demonstrated a novel approach to tyrosine production and verified the possibility to alleviate feedback inhibition by creating a phenylalanine sink.

Keywords

Phenylalanine Tyrosine Phenylalanine 4-hydroxylase Metabolic engineering 
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Notes

Acknowledgments

This work was supported by the start-up funds from the College of Engineering, University of Georgia, Athens, and a National Scientist Development Grant (11SDG6960001) from the American Heart Association.

Supplementary material

10295_2015_1591_MOESM1_ESM.docx (17 kb)
Supplementary material 1 (DOCX 16 kb)

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Copyright information

© Society for Industrial Microbiology and Biotechnology 2015

Authors and Affiliations

  1. 1.State Key Laboratory of Chemical Resource EngineeringBeijing University of Chemical TechnologyBeijingChina
  2. 2.College of EngineeringUniversity of GeorgiaAthensUSA
  3. 3.BioChemical Engineering Program, College of Engineering601B Driftmier Engineering Center, University of GeorgiaAthensUSA

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