Descripción del proyecto
Ingeniería de enzimas eficientes para la industria química
Las aminas quirales desempeñan un papel fundamental como componentes básicos de fármacos, substancia química nobles y compuestos bioactivos. El uso de amina deshidrogenasa (AmDH) en la síntesis de aminas quirales ha cobrado un gran interés debido a su potencial para abordar las limitaciones de los enfoques químicos tradicionales. El equipo del proyecto BIOSUSAMIN, financiado por el Consejo Europeo de Investigación, pretende superar las limitaciones asociadas a la estabilidad, la actividad catalítica y la gama de sustratos de la AmDH. Los investigadores utilizarán técnicas de ingeniería de proteínas para generar nuevas AmDH que produzcan una variedad de aminas y derivados con altos rendimientos y propiedades químicas precisas. El planteamiento pretende utilizar recursos renovables y minimizar el impacto ambiental, con lo que el agua es el único subproducto.
Objetivo
The objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.
Ámbito científico
- natural scienceschemical sciencesorganic chemistryalcohols
- natural scienceschemical sciencescatalysisbiocatalysis
- natural scienceschemical sciencesorganic chemistryamines
- natural sciencesearth and related environmental sciencesatmospheric sciencesclimatologyclimatic changes
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsenzymes
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
1012WX Amsterdam
Países Bajos