Process for the fermentative preparation of organic chemical compounds using coryneform bacteria in which the SugR gene is present in attenuated form

1. A recombinant coryneform bacterium comprising a SugR regulator, wherein:

a) said recombinant coryneform bacterium:

i) secretes an organic chemical compound;

ii) has the ability to utilize as a carbon source one or more of the compounds selected from the group consisting of: glucose, fructose, sucrose, and acetic acid; and

iii) comprises a feedback resistant aspartate kinase; and

b) said SugR regulator comprises all of the sequence of SEQ ID NO: 2 except for one or more differences selected from the group consisting of:

i) the amino acid at position 37 is selected from the group consisting of: L-alanine, glycine, L-isoleucine and L-proline;

ii) the amino acid at position 38 is selected from the group consisting of: L-alanine, glycine, L-isoleucine and L-proline;

iii) the amino acid at position 39 is selected from the group consisting of L-alanine, glycine, L-isoleucine and L-proline;

iv) the amino acid at position 40 is L-proline;

v) the amino acid at position 72 is selected from the group consisting of: L-alanine, glycine, L-glutamic acid and L-aspartic acid;

vi) the amino acid at position 101 is selected from the group consisting of: L-arginine, L-lysine, L-phenylalanine, L-methionine, L-glutamine, L-tryptophan, L-tyrosine and L-glutamic acid;

vii) the amino acid at position 105 is selected from the group consisting of L-proline, L-phenylalanine, L-isoleucine, L-methionine, L-glutamine, L-tryptophan and L-tyrosine;

viii) the amino acid at position 210 is selected from the group consisting of: L-alanine, L-arginine, and L-proline; and

ix) the amino acid at position 216 is selected from the group consisting of: L-alanine, L-glutamic acid, L-isoleucine and L-tryptophan.

2. The recombinant bacterium of claim 1 , wherein said organic chemical compound is selected from the group consisting of: a proteinogenic L-amino acid; L-ornithine; L-homoserine; a hydroxy acid; and a keto acid.

3. The recombinant bacterium of claim 1 , wherein said organic chemical compound is L-lysine, L-valine or L-isoleucine.

4. The recombinant bacterium of claim 1 , wherein said recombinant bacterium is of the species Corynebacterium glutamicum.

5. The recombinant bacterium of claim 1 , wherein said recombinant coryneform bacterium is obtainable by modifying a nonrecombinant coryneform bacterium that contains an endogenous gene encoding a SugR regulator comprising the amino acid sequence of SEQ ID NO:2 and, relative to said non-recombinant bacterium, said recombinant bacterium additionally possesses one or more features selected from the group consisting of:

a) a polynucleotide which codes for an aspartate-semialdehyde dehydrogenase (Asd) is at an increased copy number or is under the control of a stronger promoter;

b) a polynucleotide which codes for a dihydrodipicolinate synthase (DapA) is at an increased copy number or is under the control of a stronger promoter;

c) a polynucleotide which codes for a dihydropicolinate reductase (DapB) is at an increased copy number or is under the control of a stronger promoter;

d) a polynucleotide which codes for a tetrahydrodipicolinate succinylase (DapD) is at an increased copy number or is under the control of a stronger promoter;

e) a polynucleotide which codes for a succinyl-aminoketopimelate transaminase (DapC) is at an increased copy number or is under the control of a stronger promoter;

f) a polynucleotide which codes for a succinyl-diaminopimelate desuccinylase (DapE) is at an increased copy number or is under the control of a stronger promoter;

g) a polynucleotide which codes for a diaminopimelate dehydrogenase (Ddh) is at an increased copy number or is under the control of a stronger promoter;

h) a polynucleotide which codes for a diaminopimelate epimerase (DapF) is at an increased copy number or is under the control of a stronger promoter;

i) a polynucleotide which codes for a diaminopimelate decarboxylase (LysA) is at an increased copy number or is under the control of a stronger promoter;

j) a polynucleotide which codes for a polypeptide having L-lysine export activity (LysE) is at an increased copy number or is under the control of a stronger promoter;

k) a polynucleotide which codes for an aspartate aminotransferase (Aat) is at an increased copy number or is under the control of a stronger promoter; and

l) a polynucleotide which codes for a pyruvate carboxylase (Pyc) is at an increased copy number or is under the control of a stronger promoter.

6. The recombinant bacterium of claim 5 , wherein said recombinant bacterium comprises a feedback resistant acetolactate synthase.

7. The recombinant bacterium of claim 5 , wherein, relative to said non-recombinant bacterium, said recombinant bacterium additionally possesses one or more features selected from the group consisting of:

a) polynucleotides which code for the small subunit (IlvN) and for the large subunit (IlvB) of acetolactate synthase (IlvBN) are at an increased copy number or are under the control of a stronger promoter;

b) a polynucleotide which codes for an isomeroreductase (IlvC) is at an increased copy number or is under the control of a stronger promoter;

c) a polynucleotide which codes for a dihydroxyacid dehydratase (IlvD) is at an increased copy number or is under the control of a stronger promoter; and

d) a polynucleotide which codes for a transaminase B (IlvE) is at an increased copy number or is under the control of a stronger promoter.

8. The recombinant bacterium of claim 5 , wherein said recombinant bacterium is of the species Corynebacterium glutamicum.

9. A recombinant coryneform bacterium comprising a gene encoding the SugR regulator of SEQ ID NO: 2, wherein:

a) said recombinant coryneform bacterium:

i) secretes an organic chemical compound;

ii) has the ability to utilize as a carbon source one or more of the compounds selected from the group consisting of: glucose, fructose, sucrose, and acetic acid; and

iii) comprises a feedback resistant aspartate kinase; and

b) said gene also comprises in its promoter region, the nucleotide sequence of all of SEQ ID NO: 13 except for one or more mutations selected from the group consisting of:

i) replacement of the nucleobase thymine at position 7 of SEQ ID NO: 13 by guanine;

ii) deletion of one or more of the nucleobases from position 2 to 7 of SEQ ID NO: 13;

iii) deletion of one or more of the nucleobases between position 52 and 57 of SEQ ID NO: 13; and

iv) replacement of one or more of the nucleobases adenine or guanine between position 52 and 57 of SEQ ID NO: 13 by thymine or cytosine.

10. The recombinant bacterium of claim 9 , wherein said gene encoding the SugR regulator of SEQ ID NO:2 comprises a start codon selected from the group consisting of GTG and TTG.

11. The recombinant bacterium of claim 9 , wherein said organic chemical compound is selected from the group consisting of: a proteinogenic L-amino acid; L-ornithine; L-homoserine; a hydroxy acid; and a keto acid.

12. The recombinant bacterium of claim 9 , wherein said organic chemical compound is L-lysine, L-valine or L-isoleucine.

13. The recombinant bacterium of claim 9 , wherein said recombinant bacterium is of the species Corynebacterium glutamicum.

14. The recombinant bacterium of claim 9 , wherein said feedback resistant aspartate kinase comprises the amino acid sequence of SEQ ID NO:8, except for one or more amino acid differences selected from the group consisting of:

a) the amino acid at position 279 of SEQ ID NO:8 is L-threonine;

b) the amino acid at position 279 of SEQ ID NO:8 is L-valine;

c) the amino acid at position 297 of SEQ ID NO:8 is L-glutamine;

d) the amino acid at position 301 of SEQ ID NO:8 is L-phenylalanine;

e) the amino acid at position 301 of SEQ ID NO:8 is L-tyrosine;

f) the amino acid at position 308 of SEQ ID NO:8 is L-isoleucine;

g) the amino acid at position 311 of SEQ ID NO:8 is L-isoleucine;

h) the amino acid at position 320 of SEQ ID NO:8 is glycine;

i) the amino acid at position 345 of SEQ ID NO:8 is L-aspartic acid;

j) the amino acid at position 380 of SEQ ID NO:8 is L-isoleucine;

k) the amino acid at position 381 of SEQ ID NO:8 is L-phenylalanine; and

l) the amino acid at position 317 of SEQ ID NO:8 is L-alanine.

15. The recombinant bacterium of claim 9 , wherein said recombinant coryneform bacterium is obtainable by modifying a non-recombinant coryneform bacterium that contains an endogenous gene encoding the SugR regulator of SEQ ID NO: 2 wherein said endogenous gene comprises in its promoter region, the nucleotide sequence of all of SEQ ID NO: 13 and, relative to said non-recombinant bacterium, said recombinant bacterium additionally possesses one or more features selected from the group consisting of:

a) a polynucleotide which codes for an aspartate-semialdehyde dehydrogenase (Asd) is at an increased copy number or is under the control of a stronger protomer;

b) a polynucleotide which codes for a dihydropicolinate synthase (DapA) is at an increased copy number or is under the control of a stronger promoter,

c) a polynucleotide which codes for a dihydropicolinate reductase (DapB) is at an increased copy number or is under the control of a stronger protomer;

d) a polynucleotide which codes for a tetrahydrodipicolinate succinylase (DapD) is at an increased copy number or is under the control of a stronger promoter;

e) a polynucleotide which codes for a succinyl-aminoketopimelate transaminase (DapC) is at increased copy number or is under the control of a stronger promoter;

f) a polynucleotide which codes for a succinyl-diaminopimelate desuccinylase (DapE) is at an increased copy number or is under the control of a stronger promoter;

g) a polynucleotide which codes for a diaminopimelate dehydrogenase (Ddh) is at an increased copy number or is under the control of a stronger promoter;

h) a polynucleotide which codes for a diaminopimelate epimerase (DapF) is at an increased copy number or is under the control of a stronger promoter;

i) a polynucleotide which codes for a diaminopimelate decarboxylase (LysA) is at an increased copy number or is under the control of a stronger promoter;

j) a polynucleotide which codes for a polypeptide having L-lysine export activity (LysE) is at an increased copy number or is under the control of a stronger promoter;

k) a polynucleotide which codes for an aspartate aminotransferase (Aat) is at an increased copy number or is under the control of a stronger promoter, and

l) a polynucleotide which codes for a pyruvate carboxylase (Pyc) is at an increased copy number or is under the control of a stronger promoter.

16. The recombinant bacterium of claim 15 , wherein said recombinant bacterium comprises a feedback resistant acetolactate synthase.

17. The recombinant bacterium of claim 15 , wherein, relative to said non-recombinant bacterium, said recombinant bacterium additionally possesses one or more features selected from the group consisting of:

a) polynucleotides which code for the small subunit (IlvN) and for the large subunit (IlvB) of acetolactate synthase (IlvBN) are at an increased copy number or are under the control of a stronger promoter;

b) a polynucleotide which codes for an isomeroreductase (IlvC) is at an increased copy number or is under the control of a stronger promoter;

c) a polynucleotide which codes for a dihydroxyacid dehydratase (IlvD) is at an increased copy number or is under the control of a stronger promoter; and

d) a polynucleotide which codes for a transaminase B (IlvE) is at an increased copy number or is under the control of a stronger promoter.

18. The recombinant bacterium of claim 15 , wherein said recombinant bacterium is of the species Corynebacterium glutamicum.