Modified microorganism for the optimized production of 2,4-dihydroxybutyrate with enhanced 2,4-dihydroxybutyrate efflux

An Escherichia coli microorganism genetically modified for producing 2,4-dihydroxybutyrate by fermentation, wherein said microorganism is genetically modified for reducing intracellular 2,4-dihydroxybutyrate accumulation, thereby optimizing 2,4-dihydroxybutyrate production, said genetic modification for reducing intracellular 2,4-dihydroxybutyrate accumulation comprising an overexpression of a gene encoding a monocarboxylate efflux system having the amino acid sequence of SEQ ID NO:

• 1 and, wherein the microorganism is genetically modified to convert at least one of the following metabolic intermediates into 2,4-dihydroxybutyrate:
• 1,2,4-butanetriol, wherein said genetic modification comprises:
• overexpression of at least one gene encoding an oxidoreductase acting on the CH—OH group of donors (EC 1.1 enzyme) having the amino acid sequence of SEQ ID NO:
• 130 or SEQ ID NO:
• 135, and
• overexpression of at least one gene encoding an oxidoreductase acting on the aldehyde or oxo group of donors (EC 1.2 enzyme) having the amino acid sequence of SEQ ID NO:140, SEQ ID NO:
• 148 or SEQ ID NO:
• 149;
• (L)-malate, wherein said genetic modification comprises:
• overexpression of at least one gene encoding a malate kinase having the amino acid sequence of SEQ ID NO:
• 198, thereby converting malate into 4-phospho-malate;
• overexpression of at least one gene encoding a malate semialdehyde dehydrogenase having the amino acid sequence of SEQ ID NO:
• 199, thereby converting 4-phospho-malate into malate-4-semialdehyde;
• and
• overexpression of at least one gene encoding a DHB dehydrogenase having the amino acid sequence SEQ ID NO:
• 200, thereby converting malate-4-semialdehyde into 2,4-dihydroxybutyrate;
• (L) malyl-CoA, wherein said genetic modification comprises:
• overexpression of at least one gene encoding a malyl-CoA reductase having the amino acid sequence of SEQ ID NO:
• 201, thereby converting malyl-CoA into malate-4-semialdehyde;
• and
• overexpression of at least one gene encoding a DHB dehydrogenase, thereby converting malate-4-semialdehyde into 2,4-dihydroxybutyrate having the amino acid sequence of SEQ ID NO:
• 200;
• and
• (L)-homoserine, wherein said genetic modification comprises:
• overexpression of at least one gene encoding a homoserine transaminase having the amino acid sequence of SEQ ID NO:
• 203, thereby converting (L)-homoserine into 2-oxo-4-hydroxybutyrate;
• and
• overexpression of at least one gene encoding a 2-oxo-4-hydroxybutyrate (OHB) reductase having the amino acid sequence of SEQ ID NO:
• 204, thereby converting 2-oxo-4-hydroxybutyrate (OHB) into 2,4-dihydroxybutyrate;
• and.