WE CLAIM
1. A coryneform bacterium having an ability to produce a heterologous multimeric
protein by secretory production,
which is modified so that expression of a gene coding for a metallopeptidase is increased as compared with a non-modified strain, and
wherein the metallopeptidase is a protein shown in the following (A) or (B):
(A) a protein having the amino acids shown in SEQ ID NO: 4,
(B) a protein having the amino acid sequence shown in SEQ ID NO: 4 including
substitution, deletion, insertion, or addition of 1 to 10 amino acid residues, and having a
property that if expression thereof is increased in the coryneform bacterium, secretory
production amount of the multimeric protein is increased compared with that observed
for a non-modified strain.
2. The coryneform bacterium as claimed in claim 1, wherein the expression of the gene is increased by increasing copy number of the gene or by modifying an expression control sequence of the gene.
3. The coryneform bacterium as claimed in claim 1 or 2, which is further modified so that the activity of a penicillin-binding protein is reduced as compared with a non-modified strain.
4. The coryneform bacterium as claimed in any one of claims 1 to 3, which is further modified so that the activity of a cell surface layer protein is reduced as compared with a non-modified strain, or which is inherently deficient in a cell surface layer protein.
5. The coryneform bacterium as claimed in any one of claims 1 to 4, which belongs to the genus Corynebactehum or Brevibactehum.
6. The coryneform bacterium as claimed in any one of claims 1 to 5, which is Corynebactehum glutamicum.

7. The coryneform bacterium as claimed in any one of claims 1 to 6,
wherein the coryneform bacterium has a genetic construct for secretory expression of the heterologous multimeric protein, and
wherein the genetic construct comprises a promoter sequence that functions in the coryneform bacterium, a nucleic acid sequence coding for a signal peptide that functions in the coryneform bacterium, which is ligated downstream from the promoter sequence, and a nucleic acid sequence coding for the heterologous multimeric protein, which is ligated downstream from the nucleic acid sequence coding for the signal peptide.
8. The coryneform bacterium as claimed in any one of claims 1 to 7, wherein the heterologous multimeric protein is an antibody-related molecule.
9. The coryneform bacterium as claimed in claim 8, wherein the antibody-related molecule consists of one or more proteins selected from Fab, F(ab')2, and Fc fusion protein.
10. The coryneform bacterium as claimed in any one of claims 1 to 7, wherein the heterologous multimeric protein is the vascular endothelial cell growth factor A (VEGF-A).
11. A method for producing a heterologous multimeric protein comprising:
culturing the coryneform bacterium as claimed in any one of claims 1 to 10; and
collecting the protein produced by secretory production.