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Enhancing aromatic amino acid production with a new method for the modification of microbial chorismate metabolism

Country of Origin: Germany
Reference Number: TODE20180525001
Publication Date: 28 May 2018

Summary

Amino acids are widely used as dietary supplements, animal feed additives and as specialty nutrients in the medical field. A German research institution developed an approach to increase yield and productivity of microbial L-tryptophan production by engineering the involved metabolic pathway regulation. An industrial partner from biotechnology and pharmaceutical industry is now sought for licensing, transfer of rights, or R&D collaboration to increase market-readiness of the process.

Description

Amino acids need to be available to the body in sufficient quantities as they are absolutely essential for every metabolic process. For this reason, aromatic amino acids, e.g. L-tryptophan (L-trp) and derivatives are widely used high-value products in food, feed, and pharmaceutical industry. L-tryptophan and other aromatic amino acids are biosynthesized from chorismate. 



Several bottlenecks impair yield and productivity of these amino acids in industrial microbial synthesis, primarily because of the complex regulations involved in the metabolic pathways, especially in the tryptophan (trp) operon as shown in the attached figure. The trp operon is strictly regulated by feedback inhibition, repression, and attenuation by the end-product L-trp.



The major problem in this regulation is the accumulation of anthranilate, which has been alleviated to some extent by state of the art approaches at the gene level, e.g. by partial expression of the trp operon genes and/or modification of the involved Indol-Glycerol-Phosphate-Synthases (IGPs).



A German research group has developed a novel method for an effective knock-out of the feed-forward inhibition of the IPGs, which has not been addressed before. Especially the enzyme TrpC has been modified to show no sensitivity for anthranilate inhibition anymore, and even positively regulated enzyme variants have been identified. Specific mutation of the the IPGs have been confirmed to lead to a significantly higher productivity at elevated anthranilate levels, since sensitivity of IGPs for anthranilate inhibition is reduced.



The process has been demonstrated at 2L lab scale with promising results, and a patent application has been filed. Therefore, an industrial partner from biotechnology and pharmaceutical industry is now sought for licensing, transfer of rights, or R&D collaboration for scaling and to increase market-readiness of the process.

Advantages and Innovations

Instead of focusing on enhancing enzymatic activity, the feed-forward inhibition in the trp operon is alleviated by engineering the IGPs, leading to a positive anthranilate regulation.



Increased yield and productivity, therefore reduced operational and capital expenditure.

Stage Of Development

Under development/lab tested

Requested partner

An industrial partner from biotechnology and pharmaceutical industry is sought for licensing, transfer of rights (pending patent), or R&D collaboration to increase market readiness of the process.



In case of a R&D collaboration the partner should have experience in the development of biotechnological processes, preferably with strong expertise in fermentation. Main task would be the scaling of the process starting from lab-scale.