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Ep 2298880 A1 (19) & (11) EP 2 298 880 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 153(4) EPC (43) Date of publication: (51) Int Cl.: 23.03.2011 Bulletin 2011/12 C12N 15/09 (2006.01) C12N 1/21 (2006.01) C12P 7/64 (2006.01) C12P 13/04 (2006.01) (2006.01) (2006.01) (21) Application number: 09722714.4 C12P 19/00 C12P 19/34 C12P 21/02 (2006.01) (22) Date of filing: 18.03.2009 (86) International application number: PCT/JP2009/055267 (87) International publication number: WO 2009/116566 (24.09.2009 Gazette 2009/39) (84) Designated Contracting States: • NAKAMURA, Noriko AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Tokyo 100-8185 (JP) HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL • MIZOGUCHI, Hiroshi PT RO SE SI SK TR Tokyo 100-8185 (JP) Designated Extension States: • MORI, Hideo AL BA RS Tokyo 194-8533 (JP) (30) Priority: 18.03.2008 JP 2008068793 (74) Representative: O’Brien, Simon Warwick D Young & Co LLP (71) Applicant: Kyowa Hakko Kirin Co., Ltd. 120 Holborn Tokyo 100-8185 (JP) London EC1N 2DY (GB) (72) Inventors: Remarks: • MASUDA, Kimie The complete document including Reference Tables Tokyo 194-0032 (JP) and the Sequence Listing can be downloaded from the EPO website (54) INDUSTRIALLY USEFUL MICROORGANISM (57) An object of the present invention is to provide cherichia coli, and a production method of a useful sub- an E. coli mutant strain having a chromosomal DNA not stance using the variant. less than 1040 kbp shorter than that of a wild-typeEs- EP 2 298 880 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 298 880 A1 Description Technical Field 5 [0001] The present invention relates to an E. coli mutant strain having chromosomal DNA shorter than that of a wild- type E. coli strain and a process for producing a useful substance using such mutant strain. Background Art 10 [0002] All nucleotide sequences of the chromosomal DNAs of E. coli have been elucidated (Non-Patent Documents 1 and 2). Also, a method wherein a given gene or a given region on chromosomal DNA of E. coli is deleted by homologous recombination has been known (Non-Patent Document 3). [0003] As reduced-genome strains defective in plural regions on the chromosome, MDS43 strain defective in 708 kbp (non-patent document 4), ∆16 strain defective in 1377 kbp (non-patent document 5) and Step28 strain defective in 1027 15 kbp (patent document 1) are already known. [0004] MDS43 strains are known to grow equivalently to wild-type Escherichia coli strain MG1655, which is a parental strain, in a minimal medium or LB medium. In addition, Step28 strain shows an increased bacterial cell amount on termination of culture as compared to parental strain W3110red strain free of defective region on the chromosome, and is known to have a high ATP regeneration activity. Moreover, threonine production using Step28T strain, wherein thre- 20 onine biosynthetic gene is reinforced, shows improved threonine productivity as compared to the use of W3110red strain. [0005] However, ∆16 strain is known to show low growth rate as compared to the parental strain, MG1655 strain. Thus, the phenotype of a reduced-genome strain varies depending on the strain, and how the deletion of a chromosomal region exceeding 1000 kbp changes the properties of Escherichia coli is difficult to predict. Therefore, Escherichia coli defective in a region of not less than 1000 kbp in the chromosomal DNA does not necessarily show useful properties. 25 [0006] In addition, an E. coli mutant, which lacks regions of 1040kbp or more on chromosomal DNA and a process for producing a useful substance using such mutant have not yet been known. non-patent document 1: Science, 277, 1453 (1997) non-patent document 2: Nucleic Acids Research, 34, 1 (2006) 30 non-patent document 3: J. Bacteriol., 180, 2063 (1998) non-patent document 4: Science, 312, 1044 (2006) non-patent document 5: Mol. Microbiol., 55, 137 (2005) patent document 1: WO2006/057341 35 Disclosure of the Invention Problems to be Solved by the Invention [0007] It is an object of the present invention to provide an industrially useful E. coli mutant strain that lacks regions 40 of 1040kbp or more on chromosomal DNA and a process for producing a useful substance using such mutant. Means of Solving the Problems [0008] The present invention relates to the following (1) - (28). 45 (1) An E. coli mutant strain comprising chromosomal DNA comprising the following genes [1] or homologous genes thereof, not comprising the genes [2] or homologous genes thereof, and being at least 1040 kbp shorter than that of a wild-type E. coli strain, provided that when the following genes [1] or homologous genes thereof comprise genes that wild-type E. coli strains do not originally contain (hereafter referred to as "NC genes"), the aforementioned E. 50 coli mutant strain derived from the wild-type E. coli strain does not necessarily have the NC gene. [1] thrL gene, thrA gene, thrB gene, thrC gene, talB gene, mog gene, htgA gene, dnaK gene, dnaJ gene, mokC gene, hokC gene, sokC gene, nhaA gene, nhaR gene, rpsT gene, ribF gene, ileS gene, lspA gene, fkpB gene, ispH gene, rihC gene, dapB gene, carA gene, carB gene, caiF gene, caiE gene, caiD gene, caiC gene, caiB 55 gene, caiA gene, caiT gene, fixA gene, fixB gene, fixC gene, fixX gene, kefF gene, kefC gene, folA gene, apaH gene, apaG gene, ksgA gene, pdxA gene, surA gene, imp gene, djlA gene, rluA gene, hepA gene, polB gene, leuD gene, leuC gene, leuB gene, leuA gene, leuL gene, leuO gene, ilvI gene, ilvH gene, fruR gene, mraZ gene, mraW gene, ftsL gene, ftsI gene, murE gene, murF gene, mraY gene, murD gene, ftsW gene, murG gene, 2 EP 2 298 880 A1 murC gene, ddlB gene, ftsQ gene, ftsA gene, ftsZ gene, lpxC gene, secM gene, secA gene, mutT gene, coaE gene, guaC gene, hofC gene, hofB gene, ppdD gene, nadC gene, ampD gene, ampE gene, aroP gene, pdhR gene, aceE gene, aceF gene, lpd gene, acnB gene, speD gene, speE gene, cueO gene, gcd gene, hpt gene, can gene, panD gene, panC gene, panB gene, htrE gene, ecpD gene, folK gene, pcnB gene, dksA gene, sfsA 5 gene, ligT gene, hrpB gene, mrcB gene, hemL gene, clcA gene, btuF gene, pfs gene, dgt gene, degP gene, cdaR gene, dapD gene, glnD gene, map gene, tff gene, rpsB gene, tsf gene, pyrH gene, frr gene, dxr gene, ispU gene, cdsA gene, hlpA gene, lpxD gene, fabZ gene, lpxA gene, lpxB gene, rnhB gene, dnaE gene, accA gene, ldcC gene, tilS gene, rof gene, nlpE gene, proS gene, rcsF gene, metQ gene, metI gene, metN gene, gmhB gene, rrsH gene, ileV gene, alaV gene, rrlH gene, rrfH gene, aspU gene, dkgB gene, mltD gene, gloB 10 gene, rnhA gene, dnaQ gene, aspV gene, ivy gene, fadE gene, lpcA gene, pepD gene, gpt gene, frsA gene, crl gene, phoE gene, proB gene, proA gene, thrW gene, hemB gene, proC gene, aroL gene, aroM gene, rdgC gene, mak gene, araJ gene, sbcC gene, sbcD gene, phoB gene, phoR gene, brnQ gene, proY gene, malZ gene, queA gene, tgt gene, secD gene, secF gene, tsx gene, ribD gene, ribE gene, nusB gene, thiL gene, pgpA gene, dxs gene, ispA gene, xseB gene, thiI gene, panE gene, cyoE gene, cyoD gene, cyoC gene, cyoB gene, 15 cyoA gene, ampG gene, bolA gene, tig gene, clpP gene, clpX gene, lon gene, hupB gene, ppiD gene, cof gene, mdlA gene, mdlB gene, glnK gene, amtB gene, tesB gene, ffs gene, maa gene, hha gene, acrB gene, acrA gene, acrR gene, kefA gene, priC gene, apt gene, dnaX gene, recR gene, htpG gene, adk gene, hemH gene, aes gene, gsk gene, fsr gene, ushA gene, copA gene, cueR gene, gcl gene, hyi gene, purK gene, purE gene, lpxH gene, ppiB gene, cysS gene, folD gene, sfmA gene, sfmC gene, sfmD gene, sfmH gene, sfmF gene, fimZ 20 gene, argU gene, entD gene, fepA gene, fes gene, entF gene, fepE gene, fepC gene, fepG gene, fepD gene, fepB gene, entC gene, entE gene, entB gene, entA gene, cstA gene, dsbG gene, ahpC gene, ahpF gene, tatE gene, lipA gene, lipB gene, dacA gene, rlpA gene, mrdB gene, mrdA gene, cobC gene, nadD gene, holA gene, rlpB gene, leuS gene, lnt gene, miaB gene, ubiF gene, glnX gene, glnV gene, metU gene, glnW gene, glnU gene, leuW gene, metT gene, asnB gene, nagD gene, nagC gene, nagA gene, nagB gene, nagE gene, glnS 25 gene, fur gene, fldA gene, seqA gene, pgm gene, potE gene, speF gene, kdpE gene, kdpD gene, kdpC gene, kdpB gene, kdpA gene, nei gene, abrB gene, gltA gene, sdhC gene, sdhD gene, sdhA gene, sdhB gene, sucA gene, sucB gene, sucC gene, sucD gene, mngR gene, mngA gene, mngB gene, cydA gene, cydB gene, tolQ gene, tolR gene, tolA gene, tolB gene, pal gene, lysT gene, valT gene, lysW gene, valZ gene, lysY gene, lysZ gene, lysQ gene, nadA gene, pnuC gene, zitB gene, aroG gene, gpmA gene, galM gene, galK gene, galT gene, 30 galE gene, modF gene, modE gene, modA gene, modB gene, mode gene, bioA gene, bioB gene, bioF gene, bioC gene, bioD gene, uvrB gene, moaA gene, moaB gene, moaC gene, moaD gene, moaE gene, rhlE gene, dps gene, rhtA gene, ompX gene, rybA gene, mntR gene, fsaA gene, moeB gene, moeA gene, iaaA gene, cmr gene, rybB gene, grxA gene, poxB gene, hcr gene, hcp gene, aqpZ gene, macA gene, macB gene, cspD gene, clpS gene, clpA gene, serW gene, infA gene, aat gene, cydC gene, cydD gene, trxB gene, lrp gene, ftsK gene, 35 lolA gene, serS gene, dmsA gene, dmsB gene, dmsC gene, pflA gene, pflB gene, focA gene, serC gene, aroA gene, cmk gene, rpsA gene, ihfB gene, msbA gene, lpxK gene, kdsB gene, smtA gene, mukF gene, mukE gene, mukB gene, aspC gene, ompF gene, asnS gene, pncB gene, pepN gene, ssuB gene, ssuC gene, ssuD gene, ssuA gene, ssuE gene, pyrD gene, uup gene, pqiA gene, pqiB gene, rmf gene, fabA gene, ompA gene, sulA gene, helD gene, mgsA gene,
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