MODIFIED ESCHERICHIA COLI STRAINS BY MEANS OF METABOLIC ENGINEERING FOR THE PRODUCTION OF (R)-3-HYDROXYBUTYRATE

The present disclosure is related to new strains of Escherichia coli and derivatives that produce (R)-3-hydroxybutyrate (R3HB) with a high performance and selectivity; said strains were genetically modified by metabolic pathway engineering to express two genes of Azotobacter vinelandii (phvA and phpbB genes) together with the overexpression of Escherichia coli (tesB gene). Also including new strains that have eliminated the pathways that compete for carbon flux for the accumulation of acetyl-CoA, and the availability of NADPH was increased by means of a Streptococcus mutans glyceraldehyde-3-phosphate dehydrogenase dependent on NADP+. Also comprises the technical solution, not obvious, to the nonspecific generation of acetic acid by thioesterase II native to Escherichia coli; requiring the generation-regeneration pathway of acetate by the phosphotransacetylase enzymes and acetate kinase, to regenerate acetyl-CoA from the acetic acid generated by TesB, in order to obtain a higher produc tion of R3HB in genetic backgrounds of Escherichia coli that allow the consumption of acetic acid. Particularly comprising fermentation processes with culture media with glucose and/or xylose, including lignocellulose hydrolysates, as a carbon source and under moderate oxygen limitation conditions, using a transformed Escherichia coli strain with the production plasmid, expressing the phbB, phbA and tesB genes in the operon. The invention also comprises novel methods of producing R3HB by overexpressing the gapNopt gene in strains of Escherichia coli with a plasmid system. La presente invención se refiere a nuevas cepas de Escherichia coli y derivadas que producen (R)-3-hidroxibutirato (R3HB) con un alto rendimiento y alta selectividad, dichas cepas se modificaron genéticamente por ingeniería de vías metabólicas para expresar dos genes de Azotobacter vinelandii (genes phbA y phbB) junto con la sobreexpresión de la tioesterasa II de E. coli (gen tesB). Además comprende nuevas cepas a las que se les eliminó las vías que compiten por el flujo de carbono para la acumulación de acetil-CoA y se les incrementó la disponibilidad de NADPH por medio de una gliceraldehído-3-fosfato deshidrogenasa dependiente de NADP+ de Streptococcus mutans. También comprende la solución técnica, no obvia a la generación inespecífica de ácido acético por la tioesterasa II nativa de E. coli; a decir de requerir la vía de generación-regeneración de acetato por las enzimas fosfotransacetilasa y acetato quin