Mutations and Genetic Targets for Enhanced L-Tyrosine Production

Technology #14252

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Inventors
Professor Gregory Stephanopoulos
Department of Chemical Engineering, MIT
External Link (bamel.scripts.mit.edu)
Christine Santos
Department of Chemical Engineering, MIT
Managed By
Jim Freedman
MIT Technology Licensing Officer - Chemicals, Instruments, Consumer Products
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Mutations and genetic targets for enhanced L-tyrosine production

US Patent 8,735,132

Applications

This technology has applications in the industrial production of L-tyrosine by microbial fermentation. L-tyrosine is a commercially important dietary supplement and a precursor for various pharmaceuticals, adhesives, pigments, and flavonoid products.

Problem Addressed

Historically, L-tyrosine was manufactured either by chemical purification from protein hydrolysates or enzymatic synthesis catalyzed by tyrosine phenol-lyase. More recently, L-tyrosine is increasingly produced by industrial fermentation involving genetically engineered E. coli strains. However, existing engineered strains used for the biosynthesis of L-tyrosine are limited in the yields achievable. Additionally, mutations and genetic targets influencing L-tyrosine production levels were not well-understood, hampering directed efforts to optimize strain characteristics. This invention demonstrates yield improvements over 150% compared to existing strains used for industrial L-tyrosine production and describes specific genetic targets for further engineering.

Technology

The Inventors made use of global Transcription Machinery Engineering (gTME) techniques to identify E. coli mutants capable of synthesizing high levels of L-tyrosine. Three mutant strains capable of producing 0.18 g of L-tyrosine per g of glucose (150% improvement over DPD4195, an existing strain used for industrial L-tyrosine production) were identified. Additionally, the specific mutations responsible for L-tyrosine overproduction were elucidated down to the nucleotide level, providing genetic targets for the development of new strains with this characteristic.

Advantages

  • 150% yield improvement compared to existing commercial strain
  • Fully defined genetic targets enables deterministic engineering of additional L-tyrosine producing strains