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Producción mejorada de aminoácidos aromáticos con un nuevo método para la modificación del metabolismo microbiano de corismato

Resumen

Tipo:
Oferta Tecnológica
Referencia:
TODE20180525001
Publicado:
13/06/2018
Caducidad:
14/06/2019
Resumen:
Un instituto de investigación alemán ha desarrollado un enfoque para incrementar el rendimiento y productividad en la producción de L-triptófano microbiano diseñando la regulación de la vía metabólica. Los aminoácidos son ampliamente utilizados como suplementos dietéticos, aditivos para piensos y nutrientes especiales en el sector médico. El L-triptófano y otros aminoácidos aromáticos son biosintetizados a partir de corismato. El instituto busca un socio en la industria farmacéutica y biotecnológica con el fin de establecer acuerdos de licencia, transferencia de derechos o cooperación en I+D e incrementar la viabilidad comercial del proceso.

Details

Tittle:
Enhancing aromatic amino acid production with a new method for the modification of microbial chorismate metabolism
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-Y-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-Y-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
IPs:
Patent(s) applied for but not yet granted

Partner sought

Type and Role of Partner Sought:
An industrial partner from biotechnology and pharmaceutical industry is sought for licensing, transfer of rights (pending patent), or R-Y-D collaboration to increase market readiness of the process.

In case of a R-Y-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.

Client

Type and Size of Client:
R&D Institution
Already Engaged in Trans-National Cooperation:
No
Languages Spoken:
English
German

Keywords

Technology Keywords:
08001002 Aditivos / ingredientes alimentarios / alimentos funcionales
06002006 Biología sintética
06006012 Bioprocesos
06002005 Ingeniería genética
06002008 Microbiología