Increasing methionine production by overexpressing succinate dehydrogenase
View Patent ↗The present invention relates to a process for improving the production of methionine by culturing a microorganism modified for enhancing the expression of genes involved in succinate dehydrogenase synthesis. The microorganisms were modified in a way that the methionine/carbon source yield is increased. The isolation of methionine from the fermentation medium is also claimed.
1. A method for the production of methionine, in a fermentative process comprising:
(a) culturing a microorganism modified for an improved production of methionine in an appropriate culture medium comprising a source of carbon and a source of sulfur, and
(b) recovering methionine from the culture medium, wherein said microorganism presents at least one of the following modifications:
overexpression of the genes cysP, cysU, cysW, cysA, cysM, cysJ, cysI, cysH, cysE gcvT, gcvH, gcvP, metF, metA, thrA, metH, serA, serB, serC, glyA, and/or
attenuation of the genes pykA, pykF, metJ, and purU,
and wherein said microorganism is further modified by enhancing the expression of gene(s) encoding a succinate dehydrogenase enzyme by inserting into the microorganism at least one supplementary copy of the four genes sdhA, sdhB, sdhC, and sdhD of E. coli.
2. The method of claim 1 , wherein said source of sulfur in the culture medium is sulfate, thiosulfate, hydrogen sulfide, dithionate, dithionite, sulfite or a combination thereof.
3. The method of claim 1 , wherein said source of carbon is glucose or sucrose.
4. The method of claim 1 , wherein said recovering methionine step comprises a step of isolating methionine from said culture medium.
5. The method of claim 1 , wherein said microorganism is selected from the group consisting of a bacterium, yeast and fungus.
6. The method of claim 5 , wherein said microorganism is a bacterium selected from the group consisting of Enterobacteriaceae and Coryneform bacteria.
7. The method of claim 5 , wherein said microorganism is a bacterium selected from the group consisting of E. coli and C. glutamicum.
8. The method of claim 1 , wherein said overexpression of the gene metA is overexpression of metA alleles which encode a homoserine succinyltransferase with reduced feed-back sensitivity to S-adenosylmethionine and/or methionine.
9. The method of claim 1 , wherein said overexpression of the gene thrA is overexpression of thrA alleles which encode aspartokinases/homoserine dehydrogenase with reduced feed-back inhibition to threonine.