ZA200300721B - Novel amylolytic enzyme extracted from Bacillus sp. A 7-7 (DSM 12368) and washing and cleaning agents containing this novel amylolytic enzyme. - Google Patents
Novel amylolytic enzyme extracted from Bacillus sp. A 7-7 (DSM 12368) and washing and cleaning agents containing this novel amylolytic enzyme. Download PDFInfo
- Publication number
- ZA200300721B ZA200300721B ZA200300721A ZA200300721A ZA200300721B ZA 200300721 B ZA200300721 B ZA 200300721B ZA 200300721 A ZA200300721 A ZA 200300721A ZA 200300721 A ZA200300721 A ZA 200300721A ZA 200300721 B ZA200300721 B ZA 200300721B
- Authority
- ZA
- South Africa
- Prior art keywords
- protein
- amylolytic
- derivative
- detergent
- proteins
- Prior art date
Links
- 102000004190 Enzymes Human genes 0.000 title claims description 156
- 108090000790 Enzymes Proteins 0.000 title claims description 156
- 230000003625 amylolytic effect Effects 0.000 title claims description 127
- 241000194110 Bacillus sp. (in: Bacteria) Species 0.000 title claims description 42
- 238000005406 washing Methods 0.000 title claims description 36
- 239000012459 cleaning agent Substances 0.000 title description 2
- 108090000623 proteins and genes Proteins 0.000 claims description 327
- 102000004169 proteins and genes Human genes 0.000 claims description 299
- 229940088598 enzyme Drugs 0.000 claims description 154
- 239000003599 detergent Substances 0.000 claims description 130
- 238000000034 method Methods 0.000 claims description 95
- 238000004140 cleaning Methods 0.000 claims description 66
- 238000004519 manufacturing process Methods 0.000 claims description 54
- 230000000694 effects Effects 0.000 claims description 52
- 230000008569 process Effects 0.000 claims description 51
- 108010065511 Amylases Proteins 0.000 claims description 50
- 102000013142 Amylases Human genes 0.000 claims description 50
- 235000019418 amylase Nutrition 0.000 claims description 50
- 239000004382 Amylase Substances 0.000 claims description 49
- 210000004027 cell Anatomy 0.000 claims description 43
- 229920002472 Starch Polymers 0.000 claims description 40
- 235000019698 starch Nutrition 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 38
- 239000008107 starch Substances 0.000 claims description 38
- 239000004615 ingredient Substances 0.000 claims description 35
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 31
- 150000001413 amino acids Chemical class 0.000 claims description 31
- 239000012634 fragment Substances 0.000 claims description 31
- 150000007523 nucleic acids Chemical class 0.000 claims description 30
- 239000004753 textile Substances 0.000 claims description 30
- 229940025131 amylases Drugs 0.000 claims description 29
- 108020004707 nucleic acids Proteins 0.000 claims description 29
- 102000039446 nucleic acids Human genes 0.000 claims description 29
- 239000013598 vector Substances 0.000 claims description 28
- 239000002773 nucleotide Substances 0.000 claims description 27
- 125000003729 nucleotide group Chemical group 0.000 claims description 27
- 239000012071 phase Substances 0.000 claims description 27
- 108091005804 Peptidases Proteins 0.000 claims description 24
- 102000035195 Peptidases Human genes 0.000 claims description 24
- 230000036961 partial effect Effects 0.000 claims description 24
- 239000004365 Protease Substances 0.000 claims description 23
- 241000894006 Bacteria Species 0.000 claims description 21
- 230000007062 hydrolysis Effects 0.000 claims description 21
- 238000006460 hydrolysis reaction Methods 0.000 claims description 21
- 244000005700 microbiome Species 0.000 claims description 20
- 239000000463 material Substances 0.000 claims description 19
- 230000037430 deletion Effects 0.000 claims description 15
- 238000012217 deletion Methods 0.000 claims description 15
- 238000003780 insertion Methods 0.000 claims description 15
- 230000037431 insertion Effects 0.000 claims description 15
- 230000035772 mutation Effects 0.000 claims description 15
- 239000013604 expression vector Substances 0.000 claims description 14
- 239000000470 constituent Substances 0.000 claims description 13
- 229920000858 Cyclodextrin Polymers 0.000 claims description 12
- 229940097362 cyclodextrins Drugs 0.000 claims description 12
- 241000193830 Bacillus <bacterium> Species 0.000 claims description 10
- 229920000742 Cotton Polymers 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 235000013305 food Nutrition 0.000 claims description 10
- 150000004676 glycans Chemical class 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- 229920001542 oligosaccharide Polymers 0.000 claims description 10
- 229920001282 polysaccharide Polymers 0.000 claims description 10
- 239000005017 polysaccharide Substances 0.000 claims description 10
- 239000003094 microcapsule Substances 0.000 claims description 9
- 150000002482 oligosaccharides Chemical class 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 8
- 241000588724 Escherichia coli Species 0.000 claims description 7
- 108090001060 Lipase Proteins 0.000 claims description 7
- 102000004882 Lipase Human genes 0.000 claims description 7
- 239000004367 Lipase Substances 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 235000019421 lipase Nutrition 0.000 claims description 7
- 241000193375 Bacillus alcalophilus Species 0.000 claims description 6
- 235000014469 Bacillus subtilis Nutrition 0.000 claims description 6
- 108010084185 Cellulases Proteins 0.000 claims description 6
- 102000005575 Cellulases Human genes 0.000 claims description 6
- 230000001070 adhesive effect Effects 0.000 claims description 6
- 239000002775 capsule Substances 0.000 claims description 6
- 239000013067 intermediate product Substances 0.000 claims description 6
- 239000002994 raw material Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 241000194108 Bacillus licheniformis Species 0.000 claims description 5
- 239000013543 active substance Substances 0.000 claims description 5
- 239000000853 adhesive Substances 0.000 claims description 5
- 239000000969 carrier Substances 0.000 claims description 5
- 150000003384 small molecules Chemical class 0.000 claims description 5
- 241000193744 Bacillus amyloliquefaciens Species 0.000 claims description 4
- 244000063299 Bacillus subtilis Species 0.000 claims description 4
- 238000009990 desizing Methods 0.000 claims description 4
- 235000012041 food component Nutrition 0.000 claims description 4
- 239000005417 food ingredient Substances 0.000 claims description 4
- 239000007790 solid phase Substances 0.000 claims description 4
- 241000588722 Escherichia Species 0.000 claims description 3
- 230000000890 antigenic effect Effects 0.000 claims description 3
- 239000013599 cloning vector Substances 0.000 claims description 2
- 210000003527 eukaryotic cell Anatomy 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 description 244
- 239000000203 mixture Substances 0.000 description 116
- -1 for example Proteins 0.000 description 87
- 235000002639 sodium chloride Nutrition 0.000 description 55
- 150000003839 salts Chemical class 0.000 description 42
- 150000001875 compounds Chemical class 0.000 description 41
- 230000000875 corresponding effect Effects 0.000 description 41
- 239000002253 acid Substances 0.000 description 40
- 230000006870 function Effects 0.000 description 40
- 239000002689 soil Substances 0.000 description 35
- 235000019441 ethanol Nutrition 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 235000001014 amino acid Nutrition 0.000 description 28
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 26
- 239000003112 inhibitor Substances 0.000 description 26
- 150000007513 acids Chemical class 0.000 description 24
- 239000007844 bleaching agent Substances 0.000 description 22
- 239000011734 sodium Substances 0.000 description 22
- 230000002255 enzymatic effect Effects 0.000 description 21
- 229920000642 polymer Polymers 0.000 description 21
- 229910052708 sodium Inorganic materials 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 19
- 239000000126 substance Substances 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 239000002304 perfume Substances 0.000 description 18
- 235000019832 sodium triphosphate Nutrition 0.000 description 18
- 229920002245 Dextrose equivalent Polymers 0.000 description 17
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 17
- 239000000758 substrate Substances 0.000 description 17
- 239000010457 zeolite Substances 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
- 239000002609 medium Substances 0.000 description 16
- 150000004760 silicates Chemical class 0.000 description 16
- 238000011161 development Methods 0.000 description 15
- 230000018109 developmental process Effects 0.000 description 15
- 235000014113 dietary fatty acids Nutrition 0.000 description 15
- 239000000194 fatty acid Substances 0.000 description 15
- 229930195729 fatty acid Natural products 0.000 description 15
- 150000002191 fatty alcohols Chemical class 0.000 description 15
- 108090000765 processed proteins & peptides Proteins 0.000 description 15
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 14
- 229910021536 Zeolite Inorganic materials 0.000 description 14
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 description 14
- 238000009472 formulation Methods 0.000 description 14
- 108010076504 Protein Sorting Signals Proteins 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 235000019419 proteases Nutrition 0.000 description 13
- 239000003381 stabilizer Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 12
- 239000004599 antimicrobial Substances 0.000 description 12
- 230000008901 benefit Effects 0.000 description 12
- 230000014509 gene expression Effects 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- 235000019198 oils Nutrition 0.000 description 12
- 235000000346 sugar Nutrition 0.000 description 12
- 150000001298 alcohols Chemical class 0.000 description 11
- 230000004927 fusion Effects 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 239000002736 nonionic surfactant Substances 0.000 description 11
- 102000004196 processed proteins & peptides Human genes 0.000 description 11
- 238000003860 storage Methods 0.000 description 11
- 229910019142 PO4 Inorganic materials 0.000 description 10
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 10
- 230000000845 anti-microbial effect Effects 0.000 description 10
- 229920001577 copolymer Polymers 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 150000004665 fatty acids Chemical class 0.000 description 10
- 239000006260 foam Substances 0.000 description 10
- 238000002703 mutagenesis Methods 0.000 description 10
- 231100000350 mutagenesis Toxicity 0.000 description 10
- 229920005646 polycarboxylate Polymers 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 10
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 9
- 108020004414 DNA Proteins 0.000 description 9
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 9
- 239000000975 dye Substances 0.000 description 9
- 239000004744 fabric Substances 0.000 description 9
- 230000002068 genetic effect Effects 0.000 description 9
- 238000003752 polymerase chain reaction Methods 0.000 description 9
- 239000000344 soap Substances 0.000 description 9
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 9
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 9
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 8
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000012190 activator Substances 0.000 description 8
- 229910052783 alkali metal Inorganic materials 0.000 description 8
- 239000003945 anionic surfactant Substances 0.000 description 8
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- 230000001603 reducing effect Effects 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 159000000000 sodium salts Chemical class 0.000 description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 8
- UNXRWKVEANCORM-UHFFFAOYSA-I triphosphate(5-) Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O UNXRWKVEANCORM-UHFFFAOYSA-I 0.000 description 8
- 229920001353 Dextrin Polymers 0.000 description 7
- 239000004375 Dextrin Substances 0.000 description 7
- 108091028043 Nucleic acid sequence Proteins 0.000 description 7
- 230000002378 acidificating effect Effects 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 7
- 235000019425 dextrin Nutrition 0.000 description 7
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 7
- 239000011976 maleic acid Substances 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 239000012528 membrane Substances 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 235000021317 phosphate Nutrition 0.000 description 7
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 7
- 229920000728 polyester Polymers 0.000 description 7
- 229920005862 polyol Polymers 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 239000004094 surface-active agent Substances 0.000 description 7
- 239000002562 thickening agent Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 241000192125 Firmicutes Species 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- ULUAUXLGCMPNKK-UHFFFAOYSA-N Sulfobutanedioic acid Chemical class OC(=O)CC(C(O)=O)S(O)(=O)=O ULUAUXLGCMPNKK-UHFFFAOYSA-N 0.000 description 6
- 244000299461 Theobroma cacao Species 0.000 description 6
- 239000006096 absorbing agent Substances 0.000 description 6
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 6
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 6
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 6
- 238000010170 biological method Methods 0.000 description 6
- 235000010338 boric acid Nutrition 0.000 description 6
- 229920002678 cellulose Polymers 0.000 description 6
- 235000010980 cellulose Nutrition 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 238000005457 optimization Methods 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 235000011007 phosphoric acid Nutrition 0.000 description 6
- 239000013612 plasmid Substances 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- 239000001488 sodium phosphate Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- 239000001226 triphosphate Substances 0.000 description 6
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 108010025880 Cyclomaltodextrin glucanotransferase Proteins 0.000 description 5
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 5
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 5
- 239000004952 Polyamide Substances 0.000 description 5
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 235000009470 Theobroma cacao Nutrition 0.000 description 5
- 239000007983 Tris buffer Substances 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 230000001580 bacterial effect Effects 0.000 description 5
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 5
- 235000014633 carbohydrates Nutrition 0.000 description 5
- 239000001913 cellulose Substances 0.000 description 5
- 239000007795 chemical reaction product Substances 0.000 description 5
- 238000010367 cloning Methods 0.000 description 5
- 230000007797 corrosion Effects 0.000 description 5
- 238000005260 corrosion Methods 0.000 description 5
- 239000000835 fiber Substances 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 229920002647 polyamide Polymers 0.000 description 5
- 150000003077 polyols Chemical class 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 229910052709 silver Inorganic materials 0.000 description 5
- 239000004332 silver Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 150000008163 sugars Chemical class 0.000 description 5
- 239000003760 tallow Substances 0.000 description 5
- 238000012546 transfer Methods 0.000 description 5
- 230000014616 translation Effects 0.000 description 5
- 235000013311 vegetables Nutrition 0.000 description 5
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 4
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 4
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 4
- GLZPCOQZEFWAFX-UHFFFAOYSA-N Geraniol Chemical compound CC(C)=CCCC(C)=CCO GLZPCOQZEFWAFX-UHFFFAOYSA-N 0.000 description 4
- 229920000881 Modified starch Polymers 0.000 description 4
- BGRWYDHXPHLNKA-UHFFFAOYSA-N Tetraacetylethylenediamine Chemical compound CC(=O)N(C(C)=O)CCN(C(C)=O)C(C)=O BGRWYDHXPHLNKA-UHFFFAOYSA-N 0.000 description 4
- 235000011941 Tilia x europaea Nutrition 0.000 description 4
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 4
- 125000000539 amino acid group Chemical group 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 4
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical class [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 4
- 229910001424 calcium ion Inorganic materials 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229920003086 cellulose ether Polymers 0.000 description 4
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 4
- 238000004851 dishwashing Methods 0.000 description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 4
- UKMSUNONTOPOIO-UHFFFAOYSA-N docosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC(O)=O UKMSUNONTOPOIO-UHFFFAOYSA-N 0.000 description 4
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 4
- RRAFCDWBNXTKKO-UHFFFAOYSA-N eugenol Chemical compound COC1=CC(CC=C)=CC=C1O RRAFCDWBNXTKKO-UHFFFAOYSA-N 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000001502 gel electrophoresis Methods 0.000 description 4
- 239000001963 growth medium Substances 0.000 description 4
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- 239000004571 lime Substances 0.000 description 4
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 4
- 230000002906 microbiologic effect Effects 0.000 description 4
- 235000019426 modified starch Nutrition 0.000 description 4
- 235000019796 monopotassium phosphate Nutrition 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000000123 paper Substances 0.000 description 4
- 229920000058 polyacrylate Polymers 0.000 description 4
- BITYAPCSNKJESK-UHFFFAOYSA-N potassiosodium Chemical compound [Na].[K] BITYAPCSNKJESK-UHFFFAOYSA-N 0.000 description 4
- 229960004063 propylene glycol Drugs 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 238000012163 sequencing technique Methods 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 238000006277 sulfonation reaction Methods 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 4
- 108010075550 termamyl Proteins 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 3
- WDMUXYQIMRDWRC-UHFFFAOYSA-N 2-hydroxy-3,4-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=C([N+]([O-])=O)C([N+]([O-])=O)=C1O WDMUXYQIMRDWRC-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- DBVJJBKOTRCVKF-UHFFFAOYSA-N Etidronic acid Chemical compound OP(=O)(O)C(O)(C)P(O)(O)=O DBVJJBKOTRCVKF-UHFFFAOYSA-N 0.000 description 3
- 241000233866 Fungi Species 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- 239000004115 Sodium Silicate Substances 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- 108090000787 Subtilisin Proteins 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 239000001361 adipic acid Substances 0.000 description 3
- 235000011037 adipic acid Nutrition 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 150000008051 alkyl sulfates Chemical class 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 150000008366 benzophenones Chemical class 0.000 description 3
- 235000010290 biphenyl Nutrition 0.000 description 3
- LLEMOWNGBBNAJR-UHFFFAOYSA-N biphenyl-2-ol Chemical compound OC1=CC=CC=C1C1=CC=CC=C1 LLEMOWNGBBNAJR-UHFFFAOYSA-N 0.000 description 3
- 229910021538 borax Inorganic materials 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 239000003240 coconut oil Substances 0.000 description 3
- 235000019864 coconut oil Nutrition 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000000536 complexating effect Effects 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 239000002537 cosmetic Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 150000004691 decahydrates Chemical class 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 150000001991 dicarboxylic acids Chemical class 0.000 description 3
- 239000001177 diphosphate Substances 0.000 description 3
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000000855 fermentation Methods 0.000 description 3
- 230000004151 fermentation Effects 0.000 description 3
- 239000003205 fragrance Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 238000010353 genetic engineering Methods 0.000 description 3
- 108010061330 glucan 1,4-alpha-maltohydrolase Proteins 0.000 description 3
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 229910052742 iron Inorganic materials 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- 159000000003 magnesium salts Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000000813 microbial effect Effects 0.000 description 3
- 235000013336 milk Nutrition 0.000 description 3
- 239000008267 milk Substances 0.000 description 3
- 210000004080 milk Anatomy 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 230000001590 oxidative effect Effects 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- HWGNBUXHKFFFIH-UHFFFAOYSA-I pentasodium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O HWGNBUXHKFFFIH-UHFFFAOYSA-I 0.000 description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- 239000000049 pigment Substances 0.000 description 3
- 229920006324 polyoxymethylene Polymers 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 235000011009 potassium phosphates Nutrition 0.000 description 3
- 235000019828 potassium polyphosphate Nutrition 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 238000012545 processing Methods 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 3
- AQMNWCRSESPIJM-UHFFFAOYSA-M sodium metaphosphate Chemical compound [Na+].[O-]P(=O)=O AQMNWCRSESPIJM-UHFFFAOYSA-M 0.000 description 3
- 235000019351 sodium silicates Nutrition 0.000 description 3
- 239000004328 sodium tetraborate Substances 0.000 description 3
- 235000010339 sodium tetraborate Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 238000010561 standard procedure Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 150000003512 tertiary amines Chemical class 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- ZGZHWIAQICBGKN-UHFFFAOYSA-N 1-nonanoylpyrrolidine-2,5-dione Chemical compound CCCCCCCCC(=O)N1C(=O)CCC1=O ZGZHWIAQICBGKN-UHFFFAOYSA-N 0.000 description 2
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
- RUZAHKTXOIYZNE-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(2-hydroxyethyl)amino]acetic acid;iron(2+) Chemical compound [Fe+2].OCCN(CC(O)=O)CCN(CC(O)=O)CC(O)=O RUZAHKTXOIYZNE-UHFFFAOYSA-N 0.000 description 2
- 239000004808 2-ethylhexylester Substances 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- 235000021357 Behenic acid Nutrition 0.000 description 2
- ZCTQGTTXIYCGGC-UHFFFAOYSA-N Benzyl salicylate Chemical compound OC1=CC=CC=C1C(=O)OCC1=CC=CC=C1 ZCTQGTTXIYCGGC-UHFFFAOYSA-N 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N Benzylformate Chemical compound O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
- CBOCVOKPQGJKKJ-UHFFFAOYSA-L Calcium formate Chemical compound [Ca+2].[O-]C=O.[O-]C=O CBOCVOKPQGJKKJ-UHFFFAOYSA-L 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- NPBVQXIMTZKSBA-UHFFFAOYSA-N Chavibetol Natural products COC1=CC=C(CC=C)C=C1O NPBVQXIMTZKSBA-UHFFFAOYSA-N 0.000 description 2
- 108020004705 Codon Proteins 0.000 description 2
- 108091035707 Consensus sequence Proteins 0.000 description 2
- 229920001634 Copolyester Polymers 0.000 description 2
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 229940120146 EDTMP Drugs 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical class OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 239000005770 Eugenol Substances 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 239000005792 Geraniol Substances 0.000 description 2
- GLZPCOQZEFWAFX-YFHOEESVSA-N Geraniol Natural products CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 239000005639 Lauric acid Substances 0.000 description 2
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 2
- BTJXBZZBBNNTOV-UHFFFAOYSA-N Linalyl benzoate Chemical compound CC(C)=CCCC(C)(C=C)OC(=O)C1=CC=CC=C1 BTJXBZZBBNNTOV-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- 101150054880 NASP gene Proteins 0.000 description 2
- 108091005461 Nucleic proteins Chemical group 0.000 description 2
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
- 108010064983 Ovomucin Proteins 0.000 description 2
- 235000021314 Palmitic acid Nutrition 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229920000805 Polyaspartic acid Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- UVMRYBDEERADNV-UHFFFAOYSA-N Pseudoeugenol Natural products COC1=CC(C(C)=C)=CC=C1O UVMRYBDEERADNV-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 108010056079 Subtilisins Proteins 0.000 description 2
- 102000005158 Subtilisins Human genes 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- UAOKXEHOENRFMP-ZJIFWQFVSA-N [(2r,3r,4s,5r)-2,3,4,5-tetraacetyloxy-6-oxohexyl] acetate Chemical compound CC(=O)OC[C@@H](OC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)C=O UAOKXEHOENRFMP-ZJIFWQFVSA-N 0.000 description 2
- 239000003082 abrasive agent Substances 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 2
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 2
- 150000001414 amino alcohols Chemical class 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 229940116226 behenic acid Drugs 0.000 description 2
- 229960001716 benzalkonium Drugs 0.000 description 2
- LZCZIHQBSCVGRD-UHFFFAOYSA-N benzenecarboximidamide;hydron;chloride Chemical compound [Cl-].NC(=[NH2+])C1=CC=CC=C1 LZCZIHQBSCVGRD-UHFFFAOYSA-N 0.000 description 2
- 229940077388 benzenesulfonate Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 150000001565 benzotriazoles Chemical class 0.000 description 2
- QUKGYYKBILRGFE-UHFFFAOYSA-N benzyl acetate Chemical compound CC(=O)OCC1=CC=CC=C1 QUKGYYKBILRGFE-UHFFFAOYSA-N 0.000 description 2
- AFYNADDZULBEJA-UHFFFAOYSA-N bicinchoninic acid Chemical compound C1=CC=CC2=NC(C=3C=C(C4=CC=CC=C4N=3)C(=O)O)=CC(C(O)=O)=C21 AFYNADDZULBEJA-UHFFFAOYSA-N 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 238000013452 biotechnological production Methods 0.000 description 2
- 238000004061 bleaching Methods 0.000 description 2
- 125000005619 boric acid group Chemical class 0.000 description 2
- 150000001638 boron Chemical class 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 2
- 235000011092 calcium acetate Nutrition 0.000 description 2
- 239000001639 calcium acetate Substances 0.000 description 2
- 229960005147 calcium acetate Drugs 0.000 description 2
- 235000019255 calcium formate Nutrition 0.000 description 2
- 239000004281 calcium formate Substances 0.000 description 2
- 229940044172 calcium formate Drugs 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 239000013611 chromosomal DNA Substances 0.000 description 2
- WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid Chemical class OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 2
- NEHNMFOYXAPHSD-UHFFFAOYSA-N citronellal Chemical compound O=CCC(C)CCC=C(C)C NEHNMFOYXAPHSD-UHFFFAOYSA-N 0.000 description 2
- QMVPMAAFGQKVCJ-UHFFFAOYSA-N citronellol Chemical compound OCCC(C)CCC=C(C)C QMVPMAAFGQKVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229910017052 cobalt Inorganic materials 0.000 description 2
- 239000010941 cobalt Substances 0.000 description 2
- UFMZWBIQTDUYBN-UHFFFAOYSA-N cobalt dinitrate Chemical compound [Co+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O UFMZWBIQTDUYBN-UHFFFAOYSA-N 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 230000001609 comparable effect Effects 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 230000000593 degrading effect Effects 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- UMGXUWVIJIQANV-UHFFFAOYSA-M didecyl(dimethyl)azanium;bromide Chemical compound [Br-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC UMGXUWVIJIQANV-UHFFFAOYSA-M 0.000 description 2
- 150000005690 diesters Chemical class 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 2
- 235000011180 diphosphates Nutrition 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- NFDRPXJGHKJRLJ-UHFFFAOYSA-N edtmp Chemical compound OP(O)(=O)CN(CP(O)(O)=O)CCN(CP(O)(O)=O)CP(O)(O)=O NFDRPXJGHKJRLJ-UHFFFAOYSA-N 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 229960002217 eugenol Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000019387 fatty acid methyl ester Nutrition 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 229940113087 geraniol Drugs 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000174 gluconic acid Substances 0.000 description 2
- 235000012208 gluconic acid Nutrition 0.000 description 2
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 150000002357 guanidines Chemical class 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910001385 heavy metal Inorganic materials 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 2
- PMYUVOOOQDGQNW-UHFFFAOYSA-N hexasodium;trioxido(trioxidosilyloxy)silane Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-][Si]([O-])([O-])O[Si]([O-])([O-])[O-] PMYUVOOOQDGQNW-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229930002839 ionone Natural products 0.000 description 2
- 150000002499 ionone derivatives Chemical class 0.000 description 2
- 238000001155 isoelectric focusing Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 2
- 108010052968 leupeptin Proteins 0.000 description 2
- 229920005610 lignin Polymers 0.000 description 2
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 2
- CDOSHBSSFJOMGT-UHFFFAOYSA-N linalool Chemical compound CC(C)=CCCC(C)(O)C=C CDOSHBSSFJOMGT-UHFFFAOYSA-N 0.000 description 2
- UWKAYLJWKGQEPM-LBPRGKRZSA-N linalyl acetate Chemical compound CC(C)=CCC[C@](C)(C=C)OC(C)=O UWKAYLJWKGQEPM-LBPRGKRZSA-N 0.000 description 2
- 239000004325 lysozyme Substances 0.000 description 2
- 235000010335 lysozyme Nutrition 0.000 description 2
- 229960000274 lysozyme Drugs 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 229910044991 metal oxide Inorganic materials 0.000 description 2
- 150000004706 metal oxides Chemical class 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 108010020132 microbial serine proteinases Proteins 0.000 description 2
- 238000010369 molecular cloning Methods 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- HHFDXDXLAINLOT-UHFFFAOYSA-N n,n'-dioctadecylethane-1,2-diamine Chemical compound CCCCCCCCCCCCCCCCCCNCCNCCCCCCCCCCCCCCCCCC HHFDXDXLAINLOT-UHFFFAOYSA-N 0.000 description 2
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 2
- 239000002088 nanocapsule Substances 0.000 description 2
- 239000005445 natural material Substances 0.000 description 2
- 229920005615 natural polymer Polymers 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 2
- 125000006353 oxyethylene group Chemical group 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 239000003346 palm kernel oil Substances 0.000 description 2
- 235000019865 palm kernel oil Nutrition 0.000 description 2
- 235000019831 pentapotassium triphosphate Nutrition 0.000 description 2
- ATGAWOHQWWULNK-UHFFFAOYSA-I pentapotassium;[oxido(phosphonatooxy)phosphoryl] phosphate Chemical compound [K+].[K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O ATGAWOHQWWULNK-UHFFFAOYSA-I 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- MDHYEMXUFSJLGV-UHFFFAOYSA-N phenethyl acetate Chemical compound CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 2
- 150000002989 phenols Chemical class 0.000 description 2
- PATMLLNMTPIUSY-UHFFFAOYSA-N phenoxysulfonyl 7-methyloctanoate Chemical compound CC(C)CCCCCC(=O)OS(=O)(=O)OC1=CC=CC=C1 PATMLLNMTPIUSY-UHFFFAOYSA-N 0.000 description 2
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920000172 poly(styrenesulfonic acid) Polymers 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000011241 protective layer Substances 0.000 description 2
- 230000006337 proteolytic cleavage Effects 0.000 description 2
- 238000006268 reductive amination reaction Methods 0.000 description 2
- 239000005871 repellent Substances 0.000 description 2
- 230000002940 repellent Effects 0.000 description 2
- 108091008146 restriction endonucleases Proteins 0.000 description 2
- 150000003902 salicylic acid esters Chemical class 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 150000004671 saturated fatty acids Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 238000004513 sizing Methods 0.000 description 2
- GCLGEJMYGQKIIW-UHFFFAOYSA-H sodium hexametaphosphate Chemical compound [Na]OP1(=O)OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])OP(=O)(O[Na])O1 GCLGEJMYGQKIIW-UHFFFAOYSA-H 0.000 description 2
- 235000019982 sodium hexametaphosphate Nutrition 0.000 description 2
- 235000019983 sodium metaphosphate Nutrition 0.000 description 2
- 239000012418 sodium perborate tetrahydrate Substances 0.000 description 2
- 235000011008 sodium phosphates Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- UGTZMIPZNRIWHX-UHFFFAOYSA-K sodium trimetaphosphate Chemical compound [Na+].[Na+].[Na+].[O-]P1(=O)OP([O-])(=O)OP([O-])(=O)O1 UGTZMIPZNRIWHX-UHFFFAOYSA-K 0.000 description 2
- IBDSNZLUHYKHQP-UHFFFAOYSA-N sodium;3-oxidodioxaborirane;tetrahydrate Chemical compound O.O.O.O.[Na+].[O-]B1OO1 IBDSNZLUHYKHQP-UHFFFAOYSA-N 0.000 description 2
- MWNQXXOSWHCCOZ-UHFFFAOYSA-L sodium;oxido carbonate Chemical compound [Na+].[O-]OC([O-])=O MWNQXXOSWHCCOZ-UHFFFAOYSA-L 0.000 description 2
- 239000013042 solid detergent Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 2
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N terephthalic acid group Chemical group C(C1=CC=C(C(=O)O)C=C1)(=O)O KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 2
- RYCLIXPGLDDLTM-UHFFFAOYSA-J tetrapotassium;phosphonato phosphate Chemical compound [K+].[K+].[K+].[K+].[O-]P([O-])(=O)OP([O-])([O-])=O RYCLIXPGLDDLTM-UHFFFAOYSA-J 0.000 description 2
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 2
- 229910052719 titanium Inorganic materials 0.000 description 2
- 239000010936 titanium Substances 0.000 description 2
- 235000010215 titanium dioxide Nutrition 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 150000003918 triazines Chemical class 0.000 description 2
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 2
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 2
- 235000019801 trisodium phosphate Nutrition 0.000 description 2
- 229960004418 trolamine Drugs 0.000 description 2
- 108010087967 type I signal peptidase Proteins 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- GPPXJZIENCGNKB-UHFFFAOYSA-N vanadium Chemical compound [V]#[V] GPPXJZIENCGNKB-UHFFFAOYSA-N 0.000 description 2
- 229920006163 vinyl copolymer Polymers 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- 239000002023 wood Substances 0.000 description 2
- 239000011787 zinc oxide Substances 0.000 description 2
- HEOCBCNFKCOKBX-RELGSGGGSA-N (1s,2e,4r)-4,7,7-trimethyl-2-[(4-methylphenyl)methylidene]bicyclo[2.2.1]heptan-3-one Chemical compound C1=CC(C)=CC=C1\C=C/1C(=O)[C@]2(C)CC[C@H]\1C2(C)C HEOCBCNFKCOKBX-RELGSGGGSA-N 0.000 description 1
- VKZRWSNIWNFCIQ-WDSKDSINSA-N (2s)-2-[2-[[(1s)-1,2-dicarboxyethyl]amino]ethylamino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NCCN[C@H](C(O)=O)CC(O)=O VKZRWSNIWNFCIQ-WDSKDSINSA-N 0.000 description 1
- OIQXFRANQVWXJF-QBFSEMIESA-N (2z)-2-benzylidene-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical compound CC1(C)C2CCC1(C)C(=O)\C2=C/C1=CC=CC=C1 OIQXFRANQVWXJF-QBFSEMIESA-N 0.000 description 1
- 239000001490 (3R)-3,7-dimethylocta-1,6-dien-3-ol Substances 0.000 description 1
- AALXZHPCKJILAZ-UHFFFAOYSA-N (4-propan-2-ylphenyl)methyl 2-hydroxybenzoate Chemical compound C1=CC(C(C)C)=CC=C1COC(=O)C1=CC=CC=C1O AALXZHPCKJILAZ-UHFFFAOYSA-N 0.000 description 1
- FFLHFURRPPIZTQ-UHFFFAOYSA-N (5-acetyloxy-2,5-dihydrofuran-2-yl) acetate Chemical compound CC(=O)OC1OC(OC(C)=O)C=C1 FFLHFURRPPIZTQ-UHFFFAOYSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- QMVPMAAFGQKVCJ-SNVBAGLBSA-N (R)-(+)-citronellol Natural products OCC[C@H](C)CCC=C(C)C QMVPMAAFGQKVCJ-SNVBAGLBSA-N 0.000 description 1
- CDOSHBSSFJOMGT-JTQLQIEISA-N (R)-linalool Natural products CC(C)=CCC[C@@](C)(O)C=C CDOSHBSSFJOMGT-JTQLQIEISA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- YYMCVDNIIFNDJK-XFQWXJFMSA-N (z)-1-(3-fluorophenyl)-n-[(z)-(3-fluorophenyl)methylideneamino]methanimine Chemical compound FC1=CC=CC(\C=N/N=C\C=2C=C(F)C=CC=2)=C1 YYMCVDNIIFNDJK-XFQWXJFMSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 description 1
- LYPVKWMHGFMDPD-UHFFFAOYSA-N 1,5-diacetyl-1,3,5-triazinane-2,4-dione Chemical compound CC(=O)N1CN(C(C)=O)C(=O)NC1=O LYPVKWMHGFMDPD-UHFFFAOYSA-N 0.000 description 1
- NPMRPDRLIHYOBW-UHFFFAOYSA-N 1-(2-butoxyethoxy)propan-2-ol Chemical compound CCCCOCCOCC(C)O NPMRPDRLIHYOBW-UHFFFAOYSA-N 0.000 description 1
- WCIQNYOXLZQQMU-UHFFFAOYSA-N 1-Phenylethyl propanoate Chemical compound CCC(=O)OC(C)C1=CC=CC=C1 WCIQNYOXLZQQMU-UHFFFAOYSA-N 0.000 description 1
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N 1-Tetradecanol Natural products CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 1
- FEFQUIPMKBPKAR-UHFFFAOYSA-N 1-benzoylazepan-2-one Chemical compound C=1C=CC=CC=1C(=O)N1CCCCCC1=O FEFQUIPMKBPKAR-UHFFFAOYSA-N 0.000 description 1
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 1
- UIEVCEQLNUHDIF-UHFFFAOYSA-N 1-chloro-2,4-dimethylbenzene Chemical group CC1=CC=C(Cl)C(C)=C1 UIEVCEQLNUHDIF-UHFFFAOYSA-N 0.000 description 1
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 description 1
- 239000001074 1-methoxy-4-[(E)-prop-1-enyl]benzene Substances 0.000 description 1
- LALVCWMSKLEQMK-UHFFFAOYSA-N 1-phenyl-3-(4-propan-2-ylphenyl)propane-1,3-dione Chemical compound C1=CC(C(C)C)=CC=C1C(=O)CC(=O)C1=CC=CC=C1 LALVCWMSKLEQMK-UHFFFAOYSA-N 0.000 description 1
- GQCZPFJGIXHZMB-UHFFFAOYSA-N 1-tert-Butoxy-2-propanol Chemical compound CC(O)COC(C)(C)C GQCZPFJGIXHZMB-UHFFFAOYSA-N 0.000 description 1
- FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
- 108020004465 16S ribosomal RNA Proteins 0.000 description 1
- TXJUTRJFNRYTHH-UHFFFAOYSA-N 1h-3,1-benzoxazine-2,4-dione Chemical compound C1=CC=C2C(=O)OC(=O)NC2=C1 TXJUTRJFNRYTHH-UHFFFAOYSA-N 0.000 description 1
- MEZZCSHVIGVWFI-UHFFFAOYSA-N 2,2'-Dihydroxy-4-methoxybenzophenone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1O MEZZCSHVIGVWFI-UHFFFAOYSA-N 0.000 description 1
- LRMSQVBRUNSOJL-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropanoic acid Chemical class OC(=O)C(F)(F)C(F)(F)F LRMSQVBRUNSOJL-UHFFFAOYSA-N 0.000 description 1
- MPJQXAIKMSKXBI-UHFFFAOYSA-N 2,7,9,14-tetraoxa-1,8-diazabicyclo[6.6.2]hexadecane-3,6,10,13-tetrone Chemical compound C1CN2OC(=O)CCC(=O)ON1OC(=O)CCC(=O)O2 MPJQXAIKMSKXBI-UHFFFAOYSA-N 0.000 description 1
- CFPOJWPDQWJEMO-UHFFFAOYSA-N 2-(1,2-dicarboxyethoxy)butanedioic acid Chemical class OC(=O)CC(C(O)=O)OC(C(O)=O)CC(O)=O CFPOJWPDQWJEMO-UHFFFAOYSA-N 0.000 description 1
- SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
- FALRKNHUBBKYCC-UHFFFAOYSA-N 2-(chloromethyl)pyridine-3-carbonitrile Chemical compound ClCC1=NC=CC=C1C#N FALRKNHUBBKYCC-UHFFFAOYSA-N 0.000 description 1
- FLUWAIIVLCVEKF-UHFFFAOYSA-N 2-Methyl-1-phenyl-2-propanyl acetate Chemical compound CC(=O)OC(C)(C)CC1=CC=CC=C1 FLUWAIIVLCVEKF-UHFFFAOYSA-N 0.000 description 1
- MJTPMXWJHPOWGH-UHFFFAOYSA-N 2-Phenoxyethyl isobutyrate Chemical compound CC(C)C(=O)OCCOC1=CC=CC=C1 MJTPMXWJHPOWGH-UHFFFAOYSA-N 0.000 description 1
- LSZBMXCYIZBZPD-UHFFFAOYSA-N 2-[(1-hydroperoxy-1-oxohexan-2-yl)carbamoyl]benzoic acid Chemical compound CCCCC(C(=O)OO)NC(=O)C1=CC=CC=C1C(O)=O LSZBMXCYIZBZPD-UHFFFAOYSA-N 0.000 description 1
- COBPKKZHLDDMTB-UHFFFAOYSA-N 2-[2-(2-butoxyethoxy)ethoxy]ethanol Chemical compound CCCCOCCOCCOCCO COBPKKZHLDDMTB-UHFFFAOYSA-N 0.000 description 1
- JTXMVXSTHSMVQF-UHFFFAOYSA-N 2-acetyloxyethyl acetate Chemical compound CC(=O)OCCOC(C)=O JTXMVXSTHSMVQF-UHFFFAOYSA-N 0.000 description 1
- NCKMMSIFQUPKCK-UHFFFAOYSA-N 2-benzyl-4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1CC1=CC=CC=C1 NCKMMSIFQUPKCK-UHFFFAOYSA-N 0.000 description 1
- KXTAOXNYQGASTA-UHFFFAOYSA-N 2-benzylidenepropanedioic acid Chemical compound OC(=O)C(C(O)=O)=CC1=CC=CC=C1 KXTAOXNYQGASTA-UHFFFAOYSA-N 0.000 description 1
- DHVLDKHFGIVEIP-UHFFFAOYSA-N 2-bromo-2-(bromomethyl)pentanedinitrile Chemical compound BrCC(Br)(C#N)CCC#N DHVLDKHFGIVEIP-UHFFFAOYSA-N 0.000 description 1
- TYBHZVUFOINFDV-UHFFFAOYSA-N 2-bromo-6-[(3-bromo-5-chloro-2-hydroxyphenyl)methyl]-4-chlorophenol Chemical compound OC1=C(Br)C=C(Cl)C=C1CC1=CC(Cl)=CC(Br)=C1O TYBHZVUFOINFDV-UHFFFAOYSA-N 0.000 description 1
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical class N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 1
- GZFRVDZZXXKIGR-UHFFFAOYSA-N 2-decanoyloxybenzoic acid Chemical compound CCCCCCCCCC(=O)OC1=CC=CC=C1C(O)=O GZFRVDZZXXKIGR-UHFFFAOYSA-N 0.000 description 1
- WREFNFTVBQKRGZ-UHFFFAOYSA-N 2-decylbutanediperoxoic acid Chemical compound CCCCCCCCCCC(C(=O)OO)CC(=O)OO WREFNFTVBQKRGZ-UHFFFAOYSA-N 0.000 description 1
- ZDKYIHHSXJTDKX-UHFFFAOYSA-N 2-dodecanoyloxybenzenesulfonic acid Chemical compound CCCCCCCCCCCC(=O)OC1=CC=CC=C1S(O)(=O)=O ZDKYIHHSXJTDKX-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- JGUMTYWKIBJSTN-UHFFFAOYSA-N 2-ethylhexyl 4-[[4,6-bis[4-(2-ethylhexoxycarbonyl)anilino]-1,3,5-triazin-2-yl]amino]benzoate Chemical compound C1=CC(C(=O)OCC(CC)CCCC)=CC=C1NC1=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=NC(NC=2C=CC(=CC=2)C(=O)OCC(CC)CCCC)=N1 JGUMTYWKIBJSTN-UHFFFAOYSA-N 0.000 description 1
- WSSJONWNBBTCMG-UHFFFAOYSA-N 2-hydroxybenzoic acid (3,3,5-trimethylcyclohexyl) ester Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C1=CC=CC=C1O WSSJONWNBBTCMG-UHFFFAOYSA-N 0.000 description 1
- PYTGEDDGSASHSK-UHFFFAOYSA-N 2-iodo-4,5-dihydro-1,3-thiazole Chemical compound IC1=NCCS1 PYTGEDDGSASHSK-UHFFFAOYSA-N 0.000 description 1
- XEEYSDHEOQHCDA-UHFFFAOYSA-N 2-methylprop-2-ene-1-sulfonic acid Chemical compound CC(=C)CS(O)(=O)=O XEEYSDHEOQHCDA-UHFFFAOYSA-N 0.000 description 1
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 description 1
- YEYKMVJDLWJFOA-UHFFFAOYSA-N 2-propoxyethanol Chemical compound CCCOCCO YEYKMVJDLWJFOA-UHFFFAOYSA-N 0.000 description 1
- QCAHUFWKIQLBNB-UHFFFAOYSA-N 3-(3-methoxypropoxy)propan-1-ol Chemical group COCCCOCCCO QCAHUFWKIQLBNB-UHFFFAOYSA-N 0.000 description 1
- YNJSNEKCXVFDKW-UHFFFAOYSA-N 3-(5-amino-1h-indol-3-yl)-2-azaniumylpropanoate Chemical class C1=C(N)C=C2C(CC(N)C(O)=O)=CNC2=C1 YNJSNEKCXVFDKW-UHFFFAOYSA-N 0.000 description 1
- QGZGRCIBQRBOLJ-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[2-(n-[n-(diaminomethylidene)carbamimidoyl]-2,4-dimethylanilino)ethyl]-1-(2,4-dimethylphenyl)guanidine Chemical compound CC1=CC(C)=CC=C1N(C(=N)NC(N)=N)CCN(C(=N)NC(N)=N)C1=CC=C(C)C=C1C QGZGRCIBQRBOLJ-UHFFFAOYSA-N 0.000 description 1
- XKIPDJGUDZVSHW-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[2-(n-[n-(diaminomethylidene)carbamimidoyl]-2,5-diethoxyanilino)ethyl]-1-(2,5-diethoxyphenyl)guanidine Chemical compound CCOC1=CC=C(OCC)C(N(CCN(C(=N)NC(N)=N)C=2C(=CC=C(OCC)C=2)OCC)C(=N)NC(N)=N)=C1 XKIPDJGUDZVSHW-UHFFFAOYSA-N 0.000 description 1
- WELMRRQKVZSHOZ-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[2-(n-[n-(diaminomethylidene)carbamimidoyl]-2-methylanilino)ethyl]-1-(2-methylphenyl)guanidine Chemical compound CC1=CC=CC=C1N(C(=N)NC(N)=N)CCN(C(=N)NC(N)=N)C1=CC=CC=C1C WELMRRQKVZSHOZ-UHFFFAOYSA-N 0.000 description 1
- NROBCXIMJHPGSY-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[2-(n-[n-(diaminomethylidene)carbamimidoyl]-3,5-dimethylanilino)ethyl]-1-(3,5-dimethylphenyl)guanidine Chemical compound CC1=CC(C)=CC(N(CCN(C(=N)NC(N)=N)C=2C=C(C)C=C(C)C=2)C(=N)NC(N)=N)=C1 NROBCXIMJHPGSY-UHFFFAOYSA-N 0.000 description 1
- UQRYSYHREXBSMT-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[2-(n-[n-(diaminomethylidene)carbamimidoyl]-4-methylanilino)ethyl]-1-(4-methylphenyl)guanidine Chemical compound C1=CC(C)=CC=C1N(C(=N)NC(N)=N)CCN(C(=N)NC(N)=N)C1=CC=C(C)C=C1 UQRYSYHREXBSMT-UHFFFAOYSA-N 0.000 description 1
- XXVLGRFKGZHJFB-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[2-(n-[n-(diaminomethylidene)carbamimidoyl]anilino)ethyl]-1-phenylguanidine Chemical compound C=1C=CC=CC=1N(C(=N)NC(=N)N)CCN(C(=N)NC(N)=N)C1=CC=CC=C1 XXVLGRFKGZHJFB-UHFFFAOYSA-N 0.000 description 1
- MFALFCFWBBXSCB-UHFFFAOYSA-N 3-(diaminomethylidene)-1-[3-(n-[n-(diaminomethylidene)carbamimidoyl]-2-methylanilino)propyl]-1-(2-methylphenyl)guanidine Chemical compound CC1=CC=CC=C1N(C(=N)NC(N)=N)CCCN(C(=N)NC(N)=N)C1=CC=CC=C1C MFALFCFWBBXSCB-UHFFFAOYSA-N 0.000 description 1
- MFKRHJVUCZRDTF-UHFFFAOYSA-N 3-methoxy-3-methylbutan-1-ol Chemical compound COC(C)(C)CCO MFKRHJVUCZRDTF-UHFFFAOYSA-N 0.000 description 1
- DBTMGCOVALSLOR-UHFFFAOYSA-N 32-alpha-galactosyl-3-alpha-galactosyl-galactose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(OC2C(C(CO)OC(O)C2O)O)OC(CO)C1O DBTMGCOVALSLOR-UHFFFAOYSA-N 0.000 description 1
- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical class C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 description 1
- UNDXPKDBFOOQFC-UHFFFAOYSA-N 4-[2-nitro-4-(trifluoromethyl)phenyl]morpholine Chemical compound [O-][N+](=O)C1=CC(C(F)(F)F)=CC=C1N1CCOCC1 UNDXPKDBFOOQFC-UHFFFAOYSA-N 0.000 description 1
- 150000005418 4-aminobenzoic acid derivatives Chemical class 0.000 description 1
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 1
- LLLVZDVNHNWSDS-UHFFFAOYSA-N 4-methylidene-3,5-dioxabicyclo[5.2.2]undeca-1(9),7,10-triene-2,6-dione Chemical compound C1(C2=CC=C(C(=O)OC(=C)O1)C=C2)=O LLLVZDVNHNWSDS-UHFFFAOYSA-N 0.000 description 1
- MBZRJSQZCBXRGK-UHFFFAOYSA-N 4-tert-Butylcyclohexyl acetate Chemical compound CC(=O)OC1CCC(C(C)(C)C)CC1 MBZRJSQZCBXRGK-UHFFFAOYSA-N 0.000 description 1
- REJHVSOVQBJEBF-OWOJBTEDSA-N 5-azaniumyl-2-[(e)-2-(4-azaniumyl-2-sulfonatophenyl)ethenyl]benzenesulfonate Chemical class OS(=O)(=O)C1=CC(N)=CC=C1\C=C\C1=CC=C(N)C=C1S(O)(=O)=O REJHVSOVQBJEBF-OWOJBTEDSA-N 0.000 description 1
- XSVSPKKXQGNHMD-UHFFFAOYSA-N 5-bromo-3-methyl-1,2-thiazole Chemical compound CC=1C=C(Br)SN=1 XSVSPKKXQGNHMD-UHFFFAOYSA-N 0.000 description 1
- SFHBJXIEBWOOFA-UHFFFAOYSA-N 5-methyl-3,6-dioxabicyclo[6.2.2]dodeca-1(10),8,11-triene-2,7-dione Chemical group O=C1OC(C)COC(=O)C2=CC=C1C=C2 SFHBJXIEBWOOFA-UHFFFAOYSA-N 0.000 description 1
- CJIJXIFQYOPWTF-UHFFFAOYSA-N 7-hydroxycoumarin Natural products O1C(=O)C=CC2=CC(O)=CC=C21 CJIJXIFQYOPWTF-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical class CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 1
- 241000186361 Actinobacteria <class> Species 0.000 description 1
- 108700016155 Acyl transferases Proteins 0.000 description 1
- 102000057234 Acyl transferases Human genes 0.000 description 1
- 208000010470 Ageusia Diseases 0.000 description 1
- 229920000945 Amylopectin Polymers 0.000 description 1
- 241000186063 Arthrobacter Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000304886 Bacilli Species 0.000 description 1
- 241001328132 Bacillus horikoshii Species 0.000 description 1
- 101000740449 Bacillus subtilis (strain 168) Biotin/lipoyl attachment protein Proteins 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 241000717739 Boswellia sacra Species 0.000 description 1
- 241000186146 Brevibacterium Species 0.000 description 1
- 241000195940 Bryophyta Species 0.000 description 1
- 241000589513 Burkholderia cepacia Species 0.000 description 1
- 239000004358 Butane-1, 3-diol Substances 0.000 description 1
- WJSLZXMQHNTOBA-UHFFFAOYSA-N C(CCC(=O)O)(=O)O.C(CCC(=O)O)(=O)O.C(CCC(=O)O)(=O)O.OCC(O)CO Chemical class C(CCC(=O)O)(=O)O.C(CCC(=O)O)(=O)O.C(CCC(=O)O)(=O)O.OCC(O)CO WJSLZXMQHNTOBA-UHFFFAOYSA-N 0.000 description 1
- MEKNVKUJAZVNJW-UHFFFAOYSA-N C=1C=CC=CC=1N(C(NC(N)=N)=NCCCCCCCCC)CCN(C(NC(N)=N)=NCCCCCCCCC)C1=CC=CC=C1 Chemical compound C=1C=CC=CC=1N(C(NC(N)=N)=NCCCCCCCCC)CCN(C(NC(N)=N)=NCCCCCCCCC)C1=CC=CC=C1 MEKNVKUJAZVNJW-UHFFFAOYSA-N 0.000 description 1
- MOFDRDDDEWFZQY-UHFFFAOYSA-N C=1C=CC=CC=1N=C(NC(N)=N)N(CCCC)CCN(CCCC)C(NC(N)=N)=NC1=CC=CC=C1 Chemical compound C=1C=CC=CC=1N=C(NC(N)=N)N(CCCC)CCN(CCCC)C(NC(N)=N)=NC1=CC=CC=C1 MOFDRDDDEWFZQY-UHFFFAOYSA-N 0.000 description 1
- JMHWNJGXUIJPKG-UHFFFAOYSA-N CC(=O)O[SiH](CC=C)OC(C)=O Chemical compound CC(=O)O[SiH](CC=C)OC(C)=O JMHWNJGXUIJPKG-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 1
- 102000005701 Calcium-Binding Proteins Human genes 0.000 description 1
- 108010045403 Calcium-Binding Proteins Proteins 0.000 description 1
- 240000007436 Cananga odorata Species 0.000 description 1
- 239000005632 Capric acid (CAS 334-48-5) Substances 0.000 description 1
- 239000005635 Caprylic acid (CAS 124-07-2) Substances 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical class NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 108010059892 Cellulase Proteins 0.000 description 1
- 150000000703 Cerium Chemical class 0.000 description 1
- 229910052684 Cerium Inorganic materials 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000206575 Chondrus crispus Species 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 244000223760 Cinnamomum zeylanicum Species 0.000 description 1
- WTEVQBCEXWBHNA-UHFFFAOYSA-N Citral Natural products CC(C)=CCCC(C)=CC=O WTEVQBCEXWBHNA-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 108700010070 Codon Usage Proteins 0.000 description 1
- 241000640882 Condea Species 0.000 description 1
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 1
- 241000192700 Cyanobacteria Species 0.000 description 1
- PHOQVHQSTUBQQK-SQOUGZDYSA-N D-glucono-1,5-lactone Chemical compound OC[C@H]1OC(=O)[C@H](O)[C@@H](O)[C@@H]1O PHOQVHQSTUBQQK-SQOUGZDYSA-N 0.000 description 1
- RXVWSYJTUUKTEA-UHFFFAOYSA-N D-maltotriose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(O)C(CO)O1 RXVWSYJTUUKTEA-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 108020003215 DNA Probes Proteins 0.000 description 1
- 239000003298 DNA probe Substances 0.000 description 1
- RUPBZQFQVRMKDG-UHFFFAOYSA-M Didecyldimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC RUPBZQFQVRMKDG-UHFFFAOYSA-M 0.000 description 1
- RPNUMPOLZDHAAY-UHFFFAOYSA-N Diethylenetriamine Chemical compound NCCNCCN RPNUMPOLZDHAAY-UHFFFAOYSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 108010083608 Durazym Proteins 0.000 description 1
- 101710121765 Endo-1,4-beta-xylanase Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- FMRHJJZUHUTGKE-UHFFFAOYSA-N Ethylhexyl salicylate Chemical compound CCCCC(CC)COC(=O)C1=CC=CC=C1O FMRHJJZUHUTGKE-UHFFFAOYSA-N 0.000 description 1
- 239000004863 Frankincense Substances 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 206010064571 Gene mutation Diseases 0.000 description 1
- 241000193385 Geobacillus stearothermophilus Species 0.000 description 1
- 108010073178 Glucan 1,4-alpha-Glucosidase Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 108700023372 Glycosyltransferases Proteins 0.000 description 1
- 102000051366 Glycosyltransferases Human genes 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241001480714 Humicola insolens Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 1
- SHBUUTHKGIVMJT-UHFFFAOYSA-N Hydroxystearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OO SHBUUTHKGIVMJT-UHFFFAOYSA-N 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- HETCEOQFVDFGSY-UHFFFAOYSA-N Isopropenyl acetate Chemical compound CC(=C)OC(C)=O HETCEOQFVDFGSY-UHFFFAOYSA-N 0.000 description 1
- 235000010254 Jasminum officinale Nutrition 0.000 description 1
- 240000005385 Jasminum sambac Species 0.000 description 1
- 241000235649 Kluyveromyces Species 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- SRBFZHDQGSBBOR-HWQSCIPKSA-N L-arabinopyranose Chemical compound O[C@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-HWQSCIPKSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 108010029541 Laccase Proteins 0.000 description 1
- 108010023244 Lactoperoxidase Proteins 0.000 description 1
- 102000045576 Lactoperoxidases Human genes 0.000 description 1
- 241000234269 Liliales Species 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical class O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- KAKJTZWHIUWTTD-VQVTYTSYSA-N Met-Thr Chemical compound CSCC[C@H]([NH3+])C(=O)N[C@@H]([C@@H](C)O)C([O-])=O KAKJTZWHIUWTTD-VQVTYTSYSA-N 0.000 description 1
- QWZLBLDNRUUYQI-UHFFFAOYSA-M Methylbenzethonium chloride Chemical compound [Cl-].CC1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 QWZLBLDNRUUYQI-UHFFFAOYSA-M 0.000 description 1
- 241000192041 Micrococcus Species 0.000 description 1
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 description 1
- QISSLHPKTCLLDL-UHFFFAOYSA-N N-Acetylcaprolactam Chemical compound CC(=O)N1CCCCCC1=O QISSLHPKTCLLDL-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 125000001429 N-terminal alpha-amino-acid group Chemical group 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical group CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- YBGZDTIWKVFICR-JLHYYAGUSA-N Octyl 4-methoxycinnamic acid Chemical compound CCCCC(CC)COC(=O)\C=C\C1=CC=C(OC)C=C1 YBGZDTIWKVFICR-JLHYYAGUSA-N 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 239000004435 Oxo alcohol Substances 0.000 description 1
- WYWZRNAHINYAEF-UHFFFAOYSA-N Padimate O Chemical compound CCCCC(CC)COC(=O)C1=CC=C(N(C)C)C=C1 WYWZRNAHINYAEF-UHFFFAOYSA-N 0.000 description 1
- 235000019482 Palm oil Nutrition 0.000 description 1
- SCKXCAADGDQQCS-UHFFFAOYSA-N Performic acid Chemical compound OOC=O SCKXCAADGDQQCS-UHFFFAOYSA-N 0.000 description 1
- 108700020962 Peroxidase Proteins 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 1
- 241000203722 Pimelobacter Species 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 240000002505 Pogostemon cablin Species 0.000 description 1
- 235000011751 Pogostemon cablin Nutrition 0.000 description 1
- 229920002504 Poly(2-vinylpyridine-N-oxide) Polymers 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920001214 Polysorbate 60 Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000589630 Pseudomonas pseudoalcaligenes Species 0.000 description 1
- 241000205160 Pyrococcus Species 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 241000589180 Rhizobium Species 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 244000182022 Salvia sclarea Species 0.000 description 1
- 235000002911 Salvia sclarea Nutrition 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 241000187392 Streptomyces griseus Species 0.000 description 1
- 241000205101 Sulfolobus Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000223258 Thermomyces lanuginosus Species 0.000 description 1
- 241000589596 Thermus Species 0.000 description 1
- 239000005844 Thymol Substances 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- XEFQLINVKFYRCS-UHFFFAOYSA-N Triclosan Chemical compound OC1=CC(Cl)=CC=C1OC1=CC=C(Cl)C=C1Cl XEFQLINVKFYRCS-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 239000006035 Tryptophane Substances 0.000 description 1
- 239000004904 UV filter Substances 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 description 1
- LMETVDMCIJNNKH-UHFFFAOYSA-N [(3,7-Dimethyl-6-octenyl)oxy]acetaldehyde Chemical compound CC(C)=CCCC(C)CCOCC=O LMETVDMCIJNNKH-UHFFFAOYSA-N 0.000 description 1
- YHGREDQDBYVEOS-UHFFFAOYSA-N [acetyloxy-[2-(diacetyloxyamino)ethyl]amino] acetate Chemical class CC(=O)ON(OC(C)=O)CCN(OC(C)=O)OC(C)=O YHGREDQDBYVEOS-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 150000007960 acetonitrile Chemical class 0.000 description 1
- WFACTXCBWPYESL-UHFFFAOYSA-N acetonitrile;4-methylmorpholine Chemical compound CC#N.CN1CCOCC1 WFACTXCBWPYESL-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 108700014220 acyltransferase activity proteins Proteins 0.000 description 1
- 239000012790 adhesive layer Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000019666 ageusia Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 150000008055 alkyl aryl sulfonates Chemical class 0.000 description 1
- 125000006177 alkyl benzyl group Chemical group 0.000 description 1
- 125000005189 alkyl hydroxy group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000005263 alkylenediamine group Polymers 0.000 description 1
- 108090000637 alpha-Amylases Proteins 0.000 description 1
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 1
- 108010028144 alpha-Glucosidases Proteins 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- BNABBHGYYMZMOA-AHIHXIOASA-N alpha-maltoheptaose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](O[C@@H]2[C@H](O[C@H](O[C@@H]3[C@H](O[C@H](O[C@@H]4[C@H](O[C@H](O[C@@H]5[C@H](O[C@H](O[C@@H]6[C@H](O[C@H](O)[C@H](O)[C@H]6O)CO)[C@H](O)[C@H]5O)CO)[C@H](O)[C@H]4O)CO)[C@H](O)[C@H]3O)CO)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O BNABBHGYYMZMOA-AHIHXIOASA-N 0.000 description 1
- OCIBBXPLUVYKCH-QXVNYKTNSA-N alpha-maltohexaose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](O[C@@H]2[C@H](O[C@H](O[C@@H]3[C@H](O[C@H](O[C@@H]4[C@H](O[C@H](O[C@@H]5[C@H](O[C@H](O)[C@H](O)[C@H]5O)CO)[C@H](O)[C@H]4O)CO)[C@H](O)[C@H]3O)CO)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O OCIBBXPLUVYKCH-QXVNYKTNSA-N 0.000 description 1
- QUMXDOLUJCHOAY-UHFFFAOYSA-N alpha-methylbenzyl acetate Natural products CC(=O)OC(C)C1=CC=CC=C1 QUMXDOLUJCHOAY-UHFFFAOYSA-N 0.000 description 1
- WUOACPNHFRMFPN-UHFFFAOYSA-N alpha-terpineol Chemical compound CC1=CCC(C(C)(C)O)CC1 WUOACPNHFRMFPN-UHFFFAOYSA-N 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- UBNYRXMKIIGMKK-RMKNXTFCSA-N amiloxate Chemical compound COC1=CC=C(\C=C\C(=O)OCCC(C)C)C=C1 UBNYRXMKIIGMKK-RMKNXTFCSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 230000009604 anaerobic growth Effects 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000005571 anion exchange chromatography Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 101150010487 are gene Proteins 0.000 description 1
- 150000001491 aromatic compounds Chemical class 0.000 description 1
- VUEDNLCYHKSELL-UHFFFAOYSA-N arsonium Chemical group [AsH4+] VUEDNLCYHKSELL-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- XNEFYCZVKIDDMS-UHFFFAOYSA-N avobenzone Chemical compound C1=CC(OC)=CC=C1C(=O)CC(=O)C1=CC=C(C(C)(C)C)C=C1 XNEFYCZVKIDDMS-UHFFFAOYSA-N 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 150000003937 benzamidines Chemical class 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 229960003872 benzethonium Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 239000012965 benzophenone Substances 0.000 description 1
- UUSQFLGKGQEVCM-UHFFFAOYSA-M benzoxonium chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+](CCO)(CCO)CC1=CC=CC=C1 UUSQFLGKGQEVCM-UHFFFAOYSA-M 0.000 description 1
- 229960001574 benzoxonium chloride Drugs 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 229940007550 benzyl acetate Drugs 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- JGQFVRIQXUFPAH-UHFFFAOYSA-N beta-citronellol Natural products OCCC(C)CCCC(C)=C JGQFVRIQXUFPAH-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000002306 biochemical method Methods 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 238000011138 biotechnological process Methods 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- OHJMTUPIZMNBFR-UHFFFAOYSA-N biuret Chemical compound NC(=O)NC(N)=O OHJMTUPIZMNBFR-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- FZJUFJKVIYFBSY-UHFFFAOYSA-N bourgeonal Chemical compound CC(C)(C)C1=CC=C(CCC=O)C=C1 FZJUFJKVIYFBSY-UHFFFAOYSA-N 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- WQZQEUCNSUNRRW-UHFFFAOYSA-N butanedioic acid propane-1,2,3-triol Chemical class OCC(O)CO.OC(=O)CCC(O)=O.OC(=O)CCC(O)=O WQZQEUCNSUNRRW-UHFFFAOYSA-N 0.000 description 1
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- KHAVLLBUVKBTBG-UHFFFAOYSA-N caproleic acid Natural products OC(=O)CCCCCCCC=C KHAVLLBUVKBTBG-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001244 carboxylic acid anhydrides Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000005277 cation exchange chromatography Methods 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 229940106157 cellulase Drugs 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- ZMIGMASIKSOYAM-UHFFFAOYSA-N cerium Chemical compound [Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce][Ce] ZMIGMASIKSOYAM-UHFFFAOYSA-N 0.000 description 1
- 229960000800 cetrimonium bromide Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 150000001851 cinnamic acid derivatives Chemical class 0.000 description 1
- 235000017803 cinnamon Nutrition 0.000 description 1
- 229940043350 citral Drugs 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229930003633 citronellal Natural products 0.000 description 1
- 235000000983 citronellal Nutrition 0.000 description 1
- 235000000484 citronellol Nutrition 0.000 description 1
- 239000001524 citrus aurantium oil Substances 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 239000002734 clay mineral Substances 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- KTVIXTQDYHMGHF-UHFFFAOYSA-L cobalt(2+) sulfate Chemical compound [Co+2].[O-]S([O-])(=O)=O KTVIXTQDYHMGHF-UHFFFAOYSA-L 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 150000001896 cresols Chemical class 0.000 description 1
- 230000037029 cross reaction Effects 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 108010005400 cutinase Proteins 0.000 description 1
- 150000001912 cyanamides Chemical class 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229940019836 cyclamen aldehyde Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000002993 cycloalkylene group Chemical group 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- DIOQZVSQGTUSAI-NJFSPNSNSA-N decane Chemical class CCCCCCCCC[14CH3] DIOQZVSQGTUSAI-NJFSPNSNSA-N 0.000 description 1
- UNWDCFHEVIWFCW-UHFFFAOYSA-N decanediperoxoic acid Chemical compound OOC(=O)CCCCCCCCC(=O)OO UNWDCFHEVIWFCW-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- SQIFACVGCPWBQZ-UHFFFAOYSA-N delta-terpineol Natural products CC(C)(O)C1CCC(=C)CC1 SQIFACVGCPWBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000012933 diacyl peroxide Substances 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 1
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 1
- 235000019621 digestibility Nutrition 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 150000004683 dihydrates Chemical class 0.000 description 1
- 229940095104 dimethyl benzyl carbinyl acetate Drugs 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical class Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- GYQBBRRVRKFJRG-UHFFFAOYSA-L disodium pyrophosphate Chemical compound [Na+].[Na+].OP([O-])(=O)OP(O)([O-])=O GYQBBRRVRKFJRG-UHFFFAOYSA-L 0.000 description 1
- VTIIJXUACCWYHX-UHFFFAOYSA-L disodium;carboxylatooxy carbonate Chemical compound [Na+].[Na+].[O-]C(=O)OOC([O-])=O VTIIJXUACCWYHX-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- BRDYCNFHFWUBCZ-UHFFFAOYSA-N dodecaneperoxoic acid Chemical compound CCCCCCCCCCCC(=O)OO BRDYCNFHFWUBCZ-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000002003 electron diffraction Methods 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- UVCJGUGAGLDPAA-UHFFFAOYSA-N ensulizole Chemical compound N1C2=CC(S(=O)(=O)O)=CC=C2N=C1C1=CC=CC=C1 UVCJGUGAGLDPAA-UHFFFAOYSA-N 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- JBKVHLHDHHXQEQ-UHFFFAOYSA-N epsilon-caprolactam Chemical class O=C1CCCCCN1 JBKVHLHDHHXQEQ-UHFFFAOYSA-N 0.000 description 1
- DPUOLQHDNGRHBS-KTKRTIGZSA-N erucic acid Chemical class CCCCCCCC\C=C/CCCCCCCCCCCC(O)=O DPUOLQHDNGRHBS-KTKRTIGZSA-N 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000007046 ethoxylation reaction Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940071087 ethylenediamine disuccinate Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000001148 ferula galbaniflua oil terpeneless Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 150000002222 fluorine compounds Chemical class 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000019990 fruit wine Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- 229930182830 galactose Natural products 0.000 description 1
- 230000004034 genetic regulation Effects 0.000 description 1
- WTEVQBCEXWBHNA-JXMROGBWSA-N geranial Chemical compound CC(C)=CCC\C(C)=C\C=O WTEVQBCEXWBHNA-JXMROGBWSA-N 0.000 description 1
- 235000012209 glucono delta-lactone Nutrition 0.000 description 1
- 229960003681 gluconolactone Drugs 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 125000001046 glycoluril group Chemical group [H]C12N(*)C(=O)N(*)C1([H])N(*)C(=O)N2* 0.000 description 1
- 238000005858 glycosidation reaction Methods 0.000 description 1
- 108700014210 glycosyltransferase activity proteins Proteins 0.000 description 1
- 229940015043 glyoxal Drugs 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 229910052735 hafnium Inorganic materials 0.000 description 1
- VBJZVLUMGGDVMO-UHFFFAOYSA-N hafnium atom Chemical compound [Hf] VBJZVLUMGGDVMO-UHFFFAOYSA-N 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 108010002430 hemicellulase Proteins 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 229920013821 hydroxy alkyl cellulose Polymers 0.000 description 1
- WPFVBOQKRVRMJB-UHFFFAOYSA-N hydroxycitronellal Chemical compound O=CCC(C)CCCC(C)(C)O WPFVBOQKRVRMJB-UHFFFAOYSA-N 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical class OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000003262 industrial enzyme Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- MGFYSGNNHQQTJW-UHFFFAOYSA-N iodonium Chemical compound [IH2+] MGFYSGNNHQQTJW-UHFFFAOYSA-N 0.000 description 1
- 239000001851 juniperus communis l. berry oil Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 150000002596 lactones Chemical group 0.000 description 1
- 229940057428 lactoperoxidase Drugs 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- SDQFDHOLCGWZPU-UHFFFAOYSA-N lilial Chemical compound O=CC(C)CC1=CC=C(C(C)(C)C)C=C1 SDQFDHOLCGWZPU-UHFFFAOYSA-N 0.000 description 1
- 235000001510 limonene Nutrition 0.000 description 1
- 229940087305 limonene Drugs 0.000 description 1
- 229930007744 linalool Natural products 0.000 description 1
- UWKAYLJWKGQEPM-UHFFFAOYSA-N linalool acetate Natural products CC(C)=CCCC(C)(C=C)OC(C)=O UWKAYLJWKGQEPM-UHFFFAOYSA-N 0.000 description 1
- 230000002366 lipolytic effect Effects 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- DJMVHSOAUQHPSN-UHFFFAOYSA-N malto-hexaose Natural products OC1C(O)C(OC(C(O)CO)C(O)C(O)C=O)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(OC4C(C(O)C(O)C(CO)O4)O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 DJMVHSOAUQHPSN-UHFFFAOYSA-N 0.000 description 1
- RUJILUJOOCOSRO-WJMYNTJYSA-N maltooctaose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)O[C@H](O[C@@H]2[C@H](O[C@H](O[C@@H]3[C@H](O[C@H](O[C@@H]4[C@H](O[C@H](O[C@@H]5[C@H](O[C@H](O[C@@H]6[C@H](O[C@H](O[C@@H]7[C@H](O[C@H](O)[C@H](O)[C@H]7O)CO)[C@H](O)[C@H]6O)CO)[C@H](O)[C@H]5O)CO)[C@H](O)[C@H]4O)CO)[C@H](O)[C@H]3O)CO)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O RUJILUJOOCOSRO-WJMYNTJYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- FYGDTMLNYKFZSV-UHFFFAOYSA-N mannotriose Natural products OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(OC2C(OC(O)C(O)C2O)CO)C(O)C1O FYGDTMLNYKFZSV-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 239000001098 melissa officinalis l. leaf oil Substances 0.000 description 1
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
- 108010003855 mesentericopeptidase Proteins 0.000 description 1
- 150000002736 metal compounds Chemical class 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229940050176 methyl chloride Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 229960002285 methylbenzethonium chloride Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- MJVGBKJNTFCUJM-UHFFFAOYSA-N mexenone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=C(C)C=C1 MJVGBKJNTFCUJM-UHFFFAOYSA-N 0.000 description 1
- 239000011325 microbead Substances 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000006011 modification reaction Methods 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000011733 molybdenum Substances 0.000 description 1
- 150000005673 monoalkenes Chemical class 0.000 description 1
- 229940111688 monobasic potassium phosphate Drugs 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 235000011929 mousse Nutrition 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ZNQFZPCFVNOXJQ-UHFFFAOYSA-N n-acetyl-n-methylacetamide Chemical compound CC(=O)N(C)C(C)=O ZNQFZPCFVNOXJQ-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N n-hexadecyl alcohol Natural products CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 230000023837 negative regulation of proteolysis Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- MGFYIUFZLHCRTH-UHFFFAOYSA-N nitrilotriacetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)=O MGFYIUFZLHCRTH-UHFFFAOYSA-N 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- BEADUOQTPMBSBR-UHFFFAOYSA-N octan-2-yl 4-(dimethylamino)benzoate Chemical compound CCCCCCC(C)OC(=O)C1=CC=C(N(C)C)C=C1 BEADUOQTPMBSBR-UHFFFAOYSA-N 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- SMGTYJPMKXNQFY-UHFFFAOYSA-N octenidine dihydrochloride Chemical compound Cl.Cl.C1=CC(=NCCCCCCCC)C=CN1CCCCCCCCCCN1C=CC(=NCCCCCCCC)C=C1 SMGTYJPMKXNQFY-UHFFFAOYSA-N 0.000 description 1
- FMJSMJQBSVNSBF-UHFFFAOYSA-N octocrylene Chemical group C=1C=CC=CC=1C(=C(C#N)C(=O)OCC(CC)CCCC)C1=CC=CC=C1 FMJSMJQBSVNSBF-UHFFFAOYSA-N 0.000 description 1
- 229960000601 octocrylene Drugs 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 235000010292 orthophenyl phenol Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 235000013808 oxidized starch Nutrition 0.000 description 1
- 125000005429 oxyalkyl group Chemical group 0.000 description 1
- DXGLGDHPHMLXJC-UHFFFAOYSA-N oxybenzone Chemical compound OC1=CC(OC)=CC=C1C(=O)C1=CC=CC=C1 DXGLGDHPHMLXJC-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical class [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 description 1
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 1
- 229940070805 p-chloro-m-cresol Drugs 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011087 paperboard Substances 0.000 description 1
- RUVINXPYWBROJD-UHFFFAOYSA-N para-methoxyphenyl Natural products COC1=CC=C(C=CC)C=C1 RUVINXPYWBROJD-UHFFFAOYSA-N 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- SNGREZUHAYWORS-UHFFFAOYSA-N perfluorooctanoic acid Chemical class OC(=O)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F SNGREZUHAYWORS-UHFFFAOYSA-N 0.000 description 1
- 210000001322 periplasm Anatomy 0.000 description 1
- XCRBXWCUXJNEFX-UHFFFAOYSA-N peroxybenzoic acid Chemical compound OOC(=O)C1=CC=CC=C1 XCRBXWCUXJNEFX-UHFFFAOYSA-N 0.000 description 1
- 150000004968 peroxymonosulfuric acids Chemical class 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- XPPWLXNXHSNMKC-UHFFFAOYSA-N phenylboron Chemical class [B]C1=CC=CC=C1 XPPWLXNXHSNMKC-UHFFFAOYSA-N 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical class O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 1
- AQSJGOWTSHOLKH-UHFFFAOYSA-N phosphite(3-) Chemical class [O-]P([O-])[O-] AQSJGOWTSHOLKH-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical class C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002006 poly(N-vinylimidazole) polymer Polymers 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920000151 polyglycol Polymers 0.000 description 1
- 239000010695 polyglycol Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 150000003109 potassium Chemical class 0.000 description 1
- OQZCJRJRGMMSGK-UHFFFAOYSA-M potassium metaphosphate Chemical compound [K+].[O-]P(=O)=O OQZCJRJRGMMSGK-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- 235000011151 potassium sulphates Nutrition 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- POSICDHOUBKJKP-UHFFFAOYSA-N prop-2-enoxybenzene Chemical compound C=CCOC1=CC=CC=C1 POSICDHOUBKJKP-UHFFFAOYSA-N 0.000 description 1
- WZXKPNYMUZGZIA-UHFFFAOYSA-N propyl 3-(4-methoxyphenyl)prop-2-enoate Chemical compound CCCOC(=O)C=CC1=CC=C(OC)C=C1 WZXKPNYMUZGZIA-UHFFFAOYSA-N 0.000 description 1
- PXGPLTODNUVGFL-JZFBHDEDSA-N prostaglandin F2beta Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@@H](O)[C@@H]1C\C=C/CCCC(O)=O PXGPLTODNUVGFL-JZFBHDEDSA-N 0.000 description 1
- 238000000164 protein isolation Methods 0.000 description 1
- 230000002797 proteolythic effect Effects 0.000 description 1
- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 238000005956 quaternization reaction Methods 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000001846 repelling effect Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 230000006965 reversible inhibition Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000010671 sandalwood oil Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000003441 saturated fatty acids Nutrition 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000003352 sequestering agent Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000002893 slag Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 150000003388 sodium compounds Chemical class 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- 229940045872 sodium percarbonate Drugs 0.000 description 1
- 235000019830 sodium polyphosphate Nutrition 0.000 description 1
- 229940048086 sodium pyrophosphate Drugs 0.000 description 1
- PEVPCUFZCODDGN-UHFFFAOYSA-M sodium;2-dodecanoyloxybenzenesulfonate Chemical compound [Na+].CCCCCCCCCCCC(=O)OC1=CC=CC=C1S([O-])(=O)=O PEVPCUFZCODDGN-UHFFFAOYSA-M 0.000 description 1
- QQCFZHDSEJSLKF-UHFFFAOYSA-M sodium;4-octanoyloxybenzenesulfonate Chemical compound [Na+].CCCCCCCC(=O)OC1=CC=C(S([O-])(=O)=O)C=C1 QQCFZHDSEJSLKF-UHFFFAOYSA-M 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical class C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 229940014800 succinic anhydride Drugs 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003470 sulfuric acid monoesters Chemical class 0.000 description 1
- CXVGEDCSTKKODG-UHFFFAOYSA-N sulisobenzone Chemical compound C1=C(S(O)(=O)=O)C(OC)=CC(O)=C1C(=O)C1=CC=CC=C1 CXVGEDCSTKKODG-UHFFFAOYSA-N 0.000 description 1
- 238000004381 surface treatment Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003899 tartaric acid esters Chemical class 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KUCOHFSKRZZVRO-UHFFFAOYSA-N terephthalaldehyde Chemical compound O=CC1=CC=C(C=O)C=C1 KUCOHFSKRZZVRO-UHFFFAOYSA-N 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 229940116411 terpineol Drugs 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 150000003567 thiocyanates Chemical class 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- RUVINXPYWBROJD-ONEGZZNKSA-N trans-anethole Chemical compound COC1=CC=C(\C=C\C)C=C1 RUVINXPYWBROJD-ONEGZZNKSA-N 0.000 description 1
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 1
- LOIYMIARKYCTBW-UHFFFAOYSA-N trans-urocanic acid Natural products OC(=O)C=CC1=CNC=N1 LOIYMIARKYCTBW-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 150000003623 transition metal compounds Chemical class 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
- 150000005691 triesters Chemical class 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- JSPLKZUTYZBBKA-UHFFFAOYSA-N trioxidane Chemical group OOO JSPLKZUTYZBBKA-UHFFFAOYSA-N 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 229960004799 tryptophan Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- ORHBXUUXSCNDEV-UHFFFAOYSA-N umbelliferone Chemical compound C1=CC(=O)OC2=CC(O)=CC=C21 ORHBXUUXSCNDEV-UHFFFAOYSA-N 0.000 description 1
- HFTAFOQKODTIJY-UHFFFAOYSA-N umbelliferone Natural products Cc1cc2C=CC(=O)Oc2cc1OCC=CC(C)(C)O HFTAFOQKODTIJY-UHFFFAOYSA-N 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 241001515965 unidentified phage Species 0.000 description 1
- AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 239000010679 vetiver oil Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- ZFNVDHOSLNRHNN-UHFFFAOYSA-N xi-3-(4-Isopropylphenyl)-2-methylpropanal Chemical compound O=CC(C)CC1=CC=C(C(C)C)C=C1 ZFNVDHOSLNRHNN-UHFFFAOYSA-N 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 239000007211 ypss medium Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- 229910052726 zirconium Inorganic materials 0.000 description 1
- 229910001928 zirconium oxide Inorganic materials 0.000 description 1
- FYGDTMLNYKFZSV-BYLHFPJWSA-N β-1,4-galactotrioside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@H](CO)O[C@@H](O[C@@H]2[C@@H](O[C@@H](O)[C@H](O)[C@H]2O)CO)[C@H](O)[C@H]1O FYGDTMLNYKFZSV-BYLHFPJWSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
- C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
- C12N9/2405—Glucanases
- C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
- C12N9/2411—Amylases
- C12N9/2414—Alpha-amylase (3.2.1.1.)
- C12N9/2417—Alpha-amylase (3.2.1.1.) from microbiological source
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/386—Preparations containing enzymes, e.g. protease or amylase
Description
i AdB03s072 5 @® @ .ooxiosss 1 PCT/EP01/08359
Novel Amylolytic Enzyme Extracted from Bacillus sp. A 7-7(DSM 12368) and Washing and Cleaning Agents Containing this Novel
Amylolytic Enzyme ~~
This invention relates to a new amylolytic enzyme from the microorganism Bacillus sp. A 7-7 (DSM 12368) and sufficiently similar proteins with amylolytic activity, to processes for their production and to various potential applications for these proteins. Over and above the potential applications mentioned, they may be further developed for other, above all industrial purposes. More particularly, the present invention relates to detergents/cleaners containing such amylolytic proteins, to processes for cleaning textiles or hard surfaces in which the amylolytic proteins or corresponding compositions are involved and to their use for cleaning textiles or hard surfaces. a-Amylases (E.C. 3.2.1.1) hydrolyze internal «-1,4-glycosidic bonds of starch and starch-like polymers, such as amylose, amylopectin or glycogen for example, to form dextrins and f-1,6-branched oligosaccharides. They are among the most important industrially used enzymes. There are two reasons for this. First, like many substrate- degrading enzymes, they are released from microorganisms into the surrounding medium so that they can be isolated from the culture medium relatively easily on an industrial scale by fermentation and purification.
Second, amylases are required for a broad range of applications. | One important industrial use of a-amylase is the production of glucose syrup. Other applications are, for example, as active components in detergents/cleaners, the treatment of raw materials in textile manufacture, the production of adhesives and the production of sugar- containing foods or food ingredients.
bo adbo3sore ® [ WO 02/10356 2 PCT/EP01/08359 }
Enzymes such as proteases, amylases, lipases or cellulases have been used as active components in detergents/cleaners for decades. Their particular contribution to the washing/cleaning performance of the particular composition is, in the case of protease, an ability to degrade protein- containing soils, in the case of amylase the degradation of starch- containing soils and, in the case of lipase, its lipolytic activity. Cellulases are preferably used in detergents, above all by virtue of their contribution to the multiple wash-cycle performance of a detergent and for their fiber effect on textiles. The particular hydrolysis products are attacked, dissolved, emulsified or suspended by the other ingredients of the detergent or, by virtue of their relatively high solubility, are floated out with the wash liquor so that synergistic effects occur between the enzymes and the other constituents.
An oa-amylase commonly used in detergents/cleaners is the o-— amylase from Bacillus licheniformis. For example, the corresponding products of Novo Nordisk A/S, Bagsvaerd, Denmark and Genencor Int.,
Rochester, New York, USA are known commercially as Termamyl® and
Purastar®, respectively. The homolog isolated from B. subtilis or B. amyloliquefaciens and disclosed in US patent application US 1,227,374 is marketed by Novo Nordisk A/S under the name of BAN®.
This amylase molecule or its close relatives have been further developed in numerous inventions which addressed the problem of optimizing their enzymatic properties for specific applications through various molecular-biological modifications. Such optimizations can relate, for example, to the substrate specificities, to the stability of the enzyme under various reaction conditions or to the enzymatic activity itself. The following patent applications are mentioned as examples of such optimizations for specific applications: EP 0 410 498 for the sizing of textiles and WO 96/02633 for the liquefaction of starch.
Above all, however, a-amylases have been further developed in
@® @ 00210356 3 PCT/EP01/08359 regard to their use in detergents/cleaners. The following patent applications are mentioned as just some examples of this: the amylases of
WO 99/02702 are more stable at relatively high temperatures than the starting molecule. The enzymes of WO 99/23211 are stable at high pH values, in the presence of calcium ions and at relatively high temperatures.
The a-amylases of WO 97/43424 show a modified binding capacity for calcium ions and hence modified enzymatic properties. The mutagenesis process of WO 99/20768 leads to a-amylase variants which are particularly stable in the presence of detergent ingredients. With modifications of the type in question, a change in individual enzymatic properties almost always has an effect on other properties and on the washing performance of the particular enzyme. One example of an optimization product obtained in this way which is now on the market is Duramyl® (WO 94/02597) with reduced sensitivity to oxidation (Novo Nordisk A/S, Bagsvaerd, Denmark; SOFW-
Journal 123, (1997), pp. 723-731).
Since developments which merely comprise the optimization of only a few known starting enzymes may possibly be limited in the results obtained, there has been a parallel, intensive search for comparable enzymes from other natural sources. This search has identified starch- splitting enzymes, for example from Pimelobacter, Pseudomonas and
Thermus for food production, cosmetic and pharmaceutical products (EP 0 636 693), from Rhizobium, Arthrobacter, Brevibacterium and Micrococcus (EP 0 628 630), from Pyrococcus (WO 94/19454) and Sulfolobus for starch liquefaction at high temperatures or under highly acidic reaction conditions (EP 0 727 485 and WO 96/02633). Amylases from Bacillus sp. have been found (WO 95/26397 and WO 97/00324) for use at alkaline pH values. By virtue of their low sensitivity to detergents, other amylases from various
Bacilli (EP 0 670 367) are suitable for use in detergents/cleaners.
By virtue of their origin, enzymes from newly opened organisms are possibly more suitable than the few established enzymes for further
® ® WO 02/10356 4 PCT/EPO1/08359 development towards specific applications. One example of this is the amylase from Thermoalcalibacter (WO 98/13481) of which the natural activity is largely immune to calcium ions so that, from the outset, it has the right qualifications for use in detergents.
Further optimizations of the enzymes isolated from natural sources for the particular application can be undertaken, for example, by molecular- biological methods (for example according to US 5,171,673 or WO 99/20768) or through chemical modifications (DE 4013142). Patent application WO 99/43793, for example, describes a further development of the known Novamyl® a-amylase. In this document, sequence similarities between Novamyl® and known cyclodextrin glucanotransferases (CGTases) are used to construct a host of related molecules by microbiological techniques. These related molecules are a-amylases with additional CGTase-specific consensus sequences (boxes) and functions or, conversely, CGTases with additional regions and functions typical of a- amylases or chimeras of both molecules. The object of this development is to optimize Novamyl® for these applications.
Patent application WO 99/57250 discloses another method for improving the washing performance of detergent enzymes, such as lipases, cellulases, proteases, amylases or even CGTases. The principle described therein consists in covalently bonding the particular enzymes to cellulose binding domains (CBDs) of bacterial origin via a non-amino acid linker.
These ensure that the enzyme acts on the surface of the textile with greater intensity. WO 99/57252 includes other possible linkers in this concept while WO 99/57254 includes other enzymes such as, for example, glycosyl transferases or acyl transferases which are bound to the CBDs either to form a chimeral protein or via the linkers mentioned in WO 99/567252.
Every amylase used for detergents has its own performance profile which is reflected in the fact that some soils are removed more effectively by one enzyme while other soils are removed more effectively by another
® ® WO 02/10356 5 PCT/EP01/08359 enzyme. This further demonstrates the necessity to enrich the art with other amylolytic enzymes which also have their own performance spectra.
This necessity also arises from the changing habits and demands of the consumer, according to which there is, for example, an increasing demand for detergents for cleaning at low and medium temperatures.
In addition, new enzymes which can be obtained from organisms hitherto undeveloped for this purpose may be used as a starting product for further genetic engineering modifications by “protein engineering”. Their objective is to produce properties which the hitherto known enzymes or the detergent enzymes derived from them do not or cannot possess.
On the other hand, however, natural enzymes which, from the outset, show a certain washing or cleaning performance in conjunction with typical detergent ingredients seem to be particularly suitable candidates for such optimizations. :
Despite all these developments, however, there is still a need to find other amylolytic enzymes, which a priori have a broad application spectrum and may be used as a starting point for specific further developments, in addition to the few natural amylolytic enzymes which are actually used on an industrial scale either as such or in the form of further developments.
Accordingly, the problem addressed by the present invention was to identify a natural a-amylase hitherto undescribed which would be suitable even for industrial applications, more particularly in detergents/cleaners, or which could be used as a basis for application-specific further developments.
A secondary problem was to obtain the nucleic acid coding for such an a-amylase because this would be essential both for the biotechnological production and for the further development of these enzymes.
Another secondary problem was to find an organism which would naturally produce the particular a-amylase.
Another secondary problem was to enable the a-amylase found to
® ® WO 02/10356 6 PCT/EP01/08359 ] be biotechnologically produced.
Another secondary problem was to provide detergents/cleaners of which the washing or cleaning performance would be improved by the a- amylase found, i.e. of which the washing or cleaning performance could be atleast partly attributed to the amylolytic protein according to the invention.
Further secondary problems were to provide corresponding washing/cleaning processes and to point out corresponding potential uses.
Another secondary problem was to define further potential industrial applications for an a-amylase which, primarily, appeared suitable for use in detergents/cleaners.
The solution to the problem stated above and hence a first embodiment of the invention lies in amylolytic proteins of which the amino acid sequence is at least 96%, preferably at least 98% and more preferably 100% identical with the amino acid sequence shown in SEQ ID NO. 2, more particularly over the region which corresponds to amino acids 32 to 516 of SEQ ID NO. 2.
This includes amylolytic proteins derived from a nucleotide sequence which is at least 85%, preferably at least 90% and more preferably 100% identical with the nucleotide sequence shown in SEQ ID
NO. 1, more particularly over the region which corresponds to amino acids 32 to 516 of SEQ ID NO. 2. Also included are proteolytic enzymes which are sufficiently similar to these amyloytic proteins or which can be derived by methods known per se. Preferred representatives can naturally be isolated from microorganisms, more particularly gram-positive bacteria of the genus Bacillus, especially the species Bacillus sp. A 7-7 and more particularly Bacillus sp. A 7-7 (DSM 12368).
A second embodiment of the invention are nucleic acids coding for amylolytic proteins of which the nucleotide sequence is at least 85%, preferably at least 90% and more preferably 100% identical with the nucleotide sequence shown in SEQ ID NO. 1, more particularly over the
® [| WO 02/10356 7 PCT/EP01/08359 region which corresponds to amino acids 32 to 516 of SEQ ID NO. 2.
These preferably include — correspondingly — the nucleic acids which code for the particular proteins of the first embodiment of the invention.
A third embodiment of the invention are the natural organisms which form a protein or derivative of the first embodiment or which contain nucleic acids coding for that protein or derivative. A particularly preferred embodiment is the strain Bacillus sp. A 7-7 which has been lodged under the name DSM (12368).
A fourth embodiment of the invention are vectors with the nucleic acids of the second embodiment, host cells transformed with such vectors and any biotechnological processes for the production of a protein or derivative of the first embodiment of the invention.
A fifth embodiment of the invention are detergents/cleaners which are characterized in that they contain a protein or derivative of the first embodiment. These preferably include detergents/cleaners which contain the amylolytic protein or derivative in quantities of 0.000001% by weight to 5% by weight and more particularly 0.00001 to 3% by weight, which contain other enzymes, which are present in supply forms known per se or in which the amylolytic activity performs a function for the release of the ingredients of the detergent/cleaner or is itself controlled.
A sixth embodiment of the invention are processes for cleaning textiles or hard surfaces which are characterized in that an amylolytic protein or derivative of the first embodiment becomes active in at least one of the process steps. Detergents/cleaners of the fifth embodiment are preferably used for this purpose and the amylolytic protein or derivative is preferably used in a quantity of 0.01 mg to 200 mg per application and more particularly in a quantity of 0.02 mg to 100 mg per application in the particular process step.
A seventh embodiment of the invention are corresponding potential applications of the proteins or derivatives of the first embodiment or the
@® @® ooxiosss 8 PCT/EPO1/08359 detergents/cleaners of the fifth embodiment of the invention for cleaning textiles or hard surfaces or for releasing the ingredients of corresponding detergents/cleaners; preferably in a quantity of 0.01 mg to 200 mg and more particularly 0.02 mg to 100 mg of the amylolytic protein or derivative per application in a dishwasher or washing machine.
An eighth embodiment of the invention are further potential industrial uses for the a-amylases found. These include processes for liquefying starch, more particularly for ethanol production, temporary bonding processes and various potential applications, more particularly for the treatment of raw materials or intermediate products in textile manufacture, more particularly for desizing cotton, for the production of linear and/or short-chain oligosaccharides, for the hydrolysis of cyclodextrins, for the release of low molecular weight compounds from polysaccharide carriers or cyclodextrins, for the production of foods and/or food ingredients, for the production of animal feeds and/or animal feed ingredients and for dissolving starch-containing adhesive bonds.
A protein in the context of the present invention is a substantially linear polymer made up of the natural amino acids which generally assumes a three-dimensional structure for performing its function. In the present specification, the 19 proteinogenic, naturally occurring L-amino acids are designated by the internationally accepted 1- and 3-letter codes.
An enzyme in the context of the present invention is a protein which performs a certain biochemical function. Amylolytic proteins or enzymes with an amylolytic function are understood to be those which hydrolyze a- 1,4-glycosidic bonds of polysaccharides, more particularly those which lie within the polysaccharides. Accordingly, they are also referred to as a-1,4- amylases (E.C. 3.2.1.1).
Many proteins are formed as so-called preproteins, i.e. together with a signal peptide. By this is meant the N-terminal part of the protein of which the function generally is to guarantee the release of the protein
® ® WO 02/10356 9 PCT/EP01/08359 formed from the producing cell into the periplasm or the surrounding medium and/or its correct folding. The signal peptide is then split off from the rest of the protein under natural conditions by a signal peptidase so that it performs its actual catalytic activity without the N-terminus initially present. The native a-amylase from Bacillus sp. A7-7 (DSM 12368), for example, is 516 amino acids long, as shown in SEQ ID NO.2. As shown in
SEQ ID NO. 1, the signal peptide of this enzyme comprises 31 amino acids so that the mature enzyme has a length of 485 amino acids.
By virtue of their enzymatic activity, the mature peptides, i.e. the enzymes processed after their production, are preferred to the preproteins for industrial applications.
Proproteins are inactive precursors of proteins. Their precursors with signal frequency are known as pre-proproteins.
In the context of the present invention, nucleic acids are the molecules naturally made up of nucleotides which serve as information carriers and which code for the linear amino acid sequence in proteins or enzymes. They may be present as a single strand, as a single strand complementary to that single strand or as a double strand. As the naturally more permanent information carrier, the nucleic acid DNA is preferred for molecular biological work. By contrast, for carrying out the invention in a natural environment, for example in an expressing cell, an RNA is formed so that RNA molecules essential to the invention also represent embodiments of the invention.
With DNA, the sequences of both complementary strands in all three reading frames have to be considered. Another factor to be considered is that different codon triplets can code for the same amino acids, so that a certain amino acid sequence can be derived from several different nucleotide sequences possibly having only minimal identity (degenerateness of the genetic code). In addition, different organisms show differences in the use of this codon. For these reasons, both amino
@® ® WO 02/10356 10 PCT/EP01/08359 ] acid sequences and nucleotide sequences have to be included in the consideration of the scope of protection and disclosed nucleotide sequences should only be regarded as an exemplary coding for a certain amino acid sequence.
The unit of information corresponding to a protein is also referred to as a gene in the present specification.
With the help of methods now generally known, such as for example chemical synthesis or the polymerase chain reaction (PCR), in conjunction with molecular-biological and/or protein-chemical standard methods, the expert is able to produce the corresponding nucleic acids up to and including complete genes on the basis of known DNA and/or amino acid sequences. Such methods are known, for example, from the “Lexikon der
Biochemie”, Spektrum Akademischer Verlag, Berlin, 1999, Vol. 1, pp. 267-271 and Vol. 2., pp.227-229.
Changes in the nucleotide sequence, which can be produced for example by molecular-biological methods known per se, are referred to as mutations. Depending on the type of change, mutations are known, for example, as deletion, insertion or substitution mutations or mutations where various genes or parts of genes are fused together (“shuffling”); these are gene mutations. The associated organisms are known as mutants. The proteins derived from mutated nucleic acids are referred to as variants. For example, deletion, insertion or substitution mutations or fusions lead to deletion-, insertion-, substitution-mutated or fusion genes and, at the protein level, to corresponding deletion, insertion or substitution variants or fusion proteins.
Fragments are understood to be any proteins or peptides which are smaller than natural proteins or those which correspond to completely translated genes and which, for example, can also be synthetically obtained. On the basis of their amino acid sequences, they can be assigned to the particular complete proteins. For example, they may
@® ® WO 02/10356 11 PCT/EP01/08359 assume identical structures or may perform proteolytic activities or partial activities such as, for example, the complexing of a substrate. Fragments and deletion variants of starting proteins are basically the same. Whereas fragments are relatively small pieces, deletion mutants lack only short regions and hence only individual partial functions.
In the context of the present invention, chimeral or hybrid proteins are proteins made up of elements which naturally emanate from different polypeptide chains from the same organism or from different organisms.
This procedure is also known as shuffling or fusion mutagenesis. The object of such a fusion can be, for example, to produce or modify a certain enzymatic function with the aid of the fused-on part of the protein.
Proteins obtained by insertion mutation are understood to be variants which have been obtained by methods known per se by insertion of a nucleic acid or protein fragment into the starting sequences. Because they are basically the same, they may be assigned to the chimeral proteins from which they differ solely in the size ratio of the unchanged part of the protein to the size of the entire protein. In insertion-mutated proteins, the proportion of foreign protein is lower than in chimeral proteins.
Inversion mutagenesis, i.e. partial sequence inversion, may be regarded as a special form of both deletion and insertion. The same applies to a regrouping of various parts of the molecule which differs from the original amino acid sequence. They maybe regarded as a deletion variant, as an insertion variant and as a shuffling variant of the original protein.
Derivatives in the context of the present invention are proteins of which the pure amino acid chain has been chemically modified. Such derivatizations can be carried out, for example, biologically in connection with protein biosynthesis by the host organism. Molecular-biological methods may be used for this purpose. They may also be carried out chemically, for example by the chemical conversion of a side chain of an
® ® WO 02/10356 12 PCT/EP01/08359 ] amino acid or by covalent bonding of another compound to the protein.
This compound may be, for example, another protein which is bound to proteins according to the invention, for example by bifunctional chemical compounds. Derivatization is also understood to include covalent bonding to a macromolecular carrier.
In the context of the invention, all enzymes, proteins, fragments and derivatives come under the collective heading of proteins unless they need to be explicitly referred to as such.
Vectors in the context of the invention are understood to be elements consisting of nucleic acids which contain an interesting gene as a characteristic nucleic acid region. They are able to establish this in a species or a cell line over several generations or cell divisions as a stable genetic element which replicates independently of the rest of the genome.
Vectors are special plasmids, i.e. circular genetic elements, particularly where they are used in bacteria. In genetic engineering, a distinction is drawn between, on the one hand, vectors which are used for storage hence also for genetic work so to speak (the so-called cloning vectors) and, on the other hand, vectors which perform the function of producing the interesting gene in the host cell, i.e. facilitating the expression of the particular protein.
These vectors are known as expression vectors.
By comparison with known enzymes, which are lodged for example in generally accessible data banks, characteristic molecule parts such as structural elements, for example, or the enzymatic activity of a studied enzyme can be deduced from the amino acid or nucleotide sequence.
Such a comparison is made by assigning similar sequences in the nucleotide or amino acid sequences of the studied proteins to one another.
This is known as homologizing. A tabular assignment of the particular positions is known as alignment. In the analysis of nucleotide sequences, both complementary strands and all three possible reading frames have to be taken into consideration, as do the degenerateness of the genetic code
@® ® WO 02/10356 13 PCT/EPO1/08359 and the organism-specific codon usage. Alignments are now produced by computer programs, for example by the FASTA or BLAST algorithms; this procedure is described, for example, by D.J. Lipman and W.R. Pearson (1985) in Science, Vol. 227, pp. 1435-1441. A compilation of all positions in accord in the compared sequences is known as a consensus sequence.
Such a comparison also provides information on the similarity or homology of the compared sequences to one another. This is expressed in percent identity, i.e. the proportion of identical nucleotides or amino acid residues at the same positions. A more broadly defined notion of homology includes the conserved amino acid exchanges in this value. Percent identity then becomes percent similarity. Such assertions can be made about whole proteins or genes or only about individual regions.
Homologous regions of different proteins are generally those with the same structural elements and/or functions which can be recognized by accordances in the primary amino acid sequence. It extends to complete identities in very small regions, so-called boxes, which comprise only a few amino acids and which generally perform essential functions for the overall activity. By functions of the homologous regions are meant very small partial functions of the function performed by the protein as a whole, such as for example the formation of individual hydrogen bridge bonds for complexing a substrate or transition complex.
The enzymatic activity can be qualitatively or quantitatively modified by other regions of the protein which do not take part in the actual reaction.
This concerns, for example, the enzyme stability, activity, reaction conditions or substrate specificity.
Accordingly, the definition of an amylolytic protein according to the invention does not apply just to one with the pure function of carrying out the hydrolysis of a-1,4-glycosidic bonds which are attributable to the few amino acid residues of a probable catalytically active center. It also encompasses all the functions supporting the hydrolysis of an o-1,4-
® [ WO 02/10356 14 PCT/EP01/08359 ] glycosidic bond. Such functions can be performed, for example, by individual peptides and by one or more individual parts of a protein by acting on the actual catalytically active regions. The definition of the amylolytic function also encompasses such modifying functions alone. This is because, on the one hand, it is not known exactly which amino acid residues of the protein according to the invention actually catalyze the hydrolysis and, on the other hand, certain individual functions cannot be definitively excluded from the outset from participation in the catalysis. The auxiliary functions or partial activities include, for example, the binding of a substrate, an intermediate or end product, the activation or the inhibition or imparting of a controlling effect on the hydrolytic activity. This can also involve, for example, the formation of a structural element which lies far from the active center or a signal peptide of which the function concerns the release of the protein formed from the cell and/or its correct folding and without which no enzyme capable of functioning is generally formed in vivo.
Overall, however, a-1,4-glycosidic bonds of starch or starch-like polymers must be hydrolyzed.
The performance of an enzyme is understood to be its effectiveness in the technical field under consideration. This is based on the actual enzymatic activity, but is also dependent on other factors relevant to the particular process. These include, for example, stability, substrate binding, interaction with the material carrying the substrate or interactions with other ingredients, more particularly synergisms. For example, consideration of whether an enzyme is suitable for use in detergents will also include an assessment of its contribution to the washing or cleaning performance of a detergent or cleaner formulated with other constituents. An enzyme can be further developed and optimized for various technical applications using molecular-biological techniques known per se, more particularly those mentioned in the foregoing.
Under the Budapest Treaty over the international recognition of the
@® @® WO 02/10356 15 PCT/EP01/08359 lodging of microorganisms of 28th April, 1977, the following microorganism was lodged for the present invention in the Deutsche Sammlung von
Mikroorganismen und Zellkulturen GmbH (German Collection of
Microorganisms and Cell Cultures GmbH) in Braunschweig (DSMZ):
Bacillus sp. A 7-7. lt carries the registration number DSM 12368 (DSM 98- 587). The key data relating to the features of this biological material, as determined by the DSMZ on the lodgement date, are set out in Table 1 below.
Table 1.
Microbiological properties of Bacillus sp. A 7-7 (DSM 12368) (as determined by the DSMZ on the 9.10.1998)
Property ~~ [Result ~~]
Cell form Rodlets width [um] 3.0-45 length [um 08-10
Positive/oval
Slight swollen
Anaerobic growth pH in VP medium
Growth at 40°C Positive/weak
Growth at 50°C Negative
Growth in medium pH 7.0 Negative
NaCl 2% Positive :
NaCl 5% Positive
NaCl 7% Positive
NaCl 10% Positive
NaCl 12% Negative
NaCl 16% Negative lysozyme medium Positive
Acid from
D-glucose Negative
L-arabinose Negative
D-xylose Negative
D-mannitol Positive
® ® WO 02/10356 16 PCT/EP01/08359 ]
Hydrolysis of starch Positive gelatin Positive casein Positive tyrosine Weak
Tween 80 Positive
Tween 60 Positive
Tween 40 Positive
Tween 20 Negative
Utilization of
Propionate Positive
Remarks The physiological test results point to the species B. alcalophilus or B. horikoshii, but cannot clearly identify any of the species mentioned. The strain showed 2 colony forms which were determined as variants of one and the same species by fatty acid analysis.
Partial sequencing of the 16S rDNA produced 94.8% accordance with B. alcalophilus.
Strain A 7-7 is probably the representative of a new species.
Now, as has been surprisingly found over and above this characterization, the amylolytic enzyme produced by this strain has properties which predestine it for use in a number of industrial processes.
In addition, the strain has properties which favorably affect cultivatability.
As shown in detail in Example 2, the amylolytic enzyme according to
® ® WO 02/10356 17 PCT/EPO1/08359 the invention of the strain Bacillus sp. A 7-7 (DSM 12368) may be biochemically characterized as follows: as a mature protein, it has an apparent molecular weight of 58 kD in denaturing SDS polyacrylate gel electrophoresis whereas a molecular weight of around 59 kD can be derived from the protein sequence of 516 amino acids (SEQ ID NO. 2) and one of 55.5 kD after removal of the signal peptide comprising 31 amino acids. According to isoelectric focussing, the isoelectric point of the mature protein is 6.0. It has amylolytic activity. It is stable to incubation for 10 mins. at pH 10/50°C. 50% residual activity is observed at 60°C. The enzyme is largely stable to incubation for 10 minutes at 40°C/pH 5-12, the best stability being observed at pH 9. In the presence of 0.1% SDS, the enzyme shows 98% residual activity after incubation for 15 minutes at pH 10/50°C. In the presence of an additional 10 HPE/ml protease activity and after incubation for 15 mins. at pH 10/50°C, the enzyme still has 74% residual activity.
Accordingly, the present invention provides a naturally occurring enzyme which must be regarded as a-amylase on the strength of its sequence homologies to the hitherto known enzymes and its enzymatic activity. In principle, it may be used for any applications which require an amylolytic function. It is particularly suitable for applications involving alkaline pH values and medium temperature ranges, more particularly pH values above 9 and/or temperatures above 40°C. The application spectrum is extended by the comparatively high stability of the enzyme to detergents and proteases. Accordingly, it appears to be particularly suitable for use in detergents/cleaners.
The nucleotide sequence of this enzyme is shown in the sequence protocol under the heading SEQ ID NO. 1. Accordingly, it is available, for example, for further developments using molecular-biological methods known per se. The amino acid sequence of the enzyme is shown in the sequence protocol under the heading SEQ ID NO. 2.
® ® WO 02/10356 18 PCT/EP01/08359 ]
Comparable amylolytic proteins are also embodiments of the present invention and are claimed insofar as they have protein or DNA sequences which lie within the range of similarity to the sequences shown in SEQ ID NO. 1 and/or SEQ ID NO. 2. This similarity range encompasses all proteins of which the amino acid sequence is at least 96%, 96.5%, 97%, 97.5%, 98%, 98.5%, 99%, 99.5% or 100% identical with the amino acid sequence shown in SEQ ID NO. 2. The similarity range also encompasses all proteins of which the nucleotide sequence is at least 85%, 87.5%, 90%, 92.5%, 95%, 96%, 97%, 98%, 99% or 100% identical with the nucleotide sequence shown in SEQ ID NO. 1. This applies in particular to those partial ranges of the protein which relate to amino acids 32 to 516.
The nearest similar protein known at 17.03.2000 is the a-amylase from Baciflus alcalophilus with the registration number P 19571 in the
Swiss-Prot data bank (Geneva Bioinformatics (GeneBio) S.A., Geneva,
Switzerland; http://www.genebio.com/sprot.html). This protein has a sequence homology of 93.4% identity at protein level to the amylolytic enzyme according to the invention from Bacillus sp. A 7-7 (DSM 12368).
The protein according to the invention is clearly characterized as o- amylase through the homologous regions. Representative related proteins are presented in the alignment in Fig. 1.
On the basis of this alignment, largely the same secondary and tertiary structures may be assumed for proteins according to the invention as for the proteins used for homologizing. Their structural elements may be retrieved from generally accessible data banks such as, for example, the EMBL European Bioinformatics Institute (EB!) in Cambridge, UK (http://www. .ebi.ac.uk), Swiss-Prot or GenBank (National Center for
Biotechnology Information NCBI, National Institutes of Health, Bethesda,
MD, USA). If differing structures should appear or if it should turn out that there are various folding variants with varying amylolytic properties, for example so far as the optimal reaction conditions or the substrate
® ® WO 02/10356 19 PCT/EP01/08359 specificity is concerned, these are all included in the scope of protection of the present invention. This is because, firstly, the folding can depend upon the production conditions, for example in the presence or absence of the leader peptide. Secondly, these variants can turn out to be particularly suitable for various potential applications, for example for the quantitative liquefaction of starch, for the hydrolysis of cyclodextrins or for use in detergents/cleaners.
Particular interest attaches to the partial sequence corresponding to amino acids 32 to 516 from the sequence shown in SEQ ID NO.2. This is because, as can be concluded from the amino acid sequence, the first 31 amino acids represent a signal peptide which, in the case of production in corresponding microorganisms, probably initiates the release of the protein from the cell interior into the medium surrounding the cells. After the release, this signal peptide is split off in vivo so that the actual amylolytic activity is developed by the remaining part of the protein.
Accordingly, for the actual amylolytic function, amino acids 1 to 31 are probably of little significance, but are of importance for production and particularly for the required folding. Because of this, they cannot be excluded from the scope of protection of the present invention.
Should it turn out that there are deviations in the length of the signal peptide and/or the mature protein during production, for example by one or other bacterial strain, the claims relating to positions 1 to 31 or 32 to 516 according to SEQ ID NO. 2 apply accordingly to the corresponding variants.
For example, the transition of the protein from Bacillus sp. A 7-7 (DSM 12368) could use as many as six nucleotides before the nucleotide sequence shown in SEQ ID NO. 1. Before this probable beginning lie the six nucleotides ATG ACG. These could be translated as Met-Thr so that the signal peptide is N-terminally lengthened by two amino acids and a certain similarity to the amylase from Bacillus sp. # 707 shown in Fig. 1 under number 2 is obtained. The splitting off the signal peptide also lends
® ® WO 02/10356 20 PCT/EP01/08359 ] itself to variation.
Of the variants falling within the similarity range mentioned above, those which have optimized properties for the potential applications envisaged are particularly preferred. As explained at the beginning, such variants can be produced by methods, preferably molecular-biological methods, known per se. For example, it would also be possible to delete methionine, tryptophane, cysteine and/or tyrosine residues of proteins according to the invention and/or to replace them with less readily oxidizable amino acid residues in accordance with the teaching of WO 94/18314. Oxidation stability, the pH activity profile and/or thermal stability can be improved in this way. Further developments through point mutagenesis may also be carried, for example, in accordance with WO 99/09183 and WO 99/23211.
Fragments according to the invention are understood to be any proteins or peptides that are smaller than the proteins which correspond to those of SEQ ID NO. 1 or SEQ ID NO. 2, but are sufficiently homologous to them in the corresponding partial sequences. If they develop an amylolytic function or at least a function that supports the hydrolysis of an «-1,4- glycosidic bond, they are regarded as amylolytically active fragments and represent embodiments of the present invention. This applies, for example, to fragments which contribute to the complexing of a substrate or to the formation of a structural element necessary for the hydrolysis. The fragments may be, for example, individual domains or fragments which do not accord with the domains. Such fragments can be produced relatively inexpensively, no longer have certain possibly unfavorable characteristics of the starting molecule, such as possibly an activity-reducing regulating mechanism, or may develop a more favorable activity profile. Such protein fragments can also be produced, for example, chemically rather than biosynthetically. Chemical synthesis can be advantageous, for example, when chemical modifications are to be made after the synthesis.
® ® WO 02/10356 21 PCT/EP01/08359
By virtue of their basic similarity, proteins obtainable by deletion mutation may also be assigned to the fragments. Such proteins may largely correspond biochemically to the starting molecules or no longer have individual functions. This appears particularly appropriate, for example, in the deletion of inhibiting regions. In the final analysis, the deletions may be used both for specialization and for extending the range of application of the protein. If an amylolytic function in the broadest sense is maintained, modified, specified or even achieved in the first place in this way, the deletion variants and the fragments are proteins according to the invention. The only additional requirement in this regard is that — over and above the homologous partial sequence still present - they should lie within the above-mentioned similarity range to the sequences SEQ ID NO. 1 and
SEQ ID NO. 2.
For example, it is possible in accordance with WO 99/57250 to provide a protein according to the invention or parts thereof with binding domains from other proteins via peptidic or nonpeptidic linkers and thus to make hydrolysis of the substrate more effective. Such constructs fall within the scope of protection of the present invention when they develop amylolytic activities and those parts of the construct which perform this function are sufficiently similar to the stated sequences according to the invention. Equally, amylolytic proteins according to the invention may also be linked, for example, to proteases in order to perform a double function.
The proteins and signal peptides obtainable from preproteins by splitting off the N-terminal amino acids may also be regarded as naturally formed fragments or deletion-mutated proteins. A splitting mechanism such as this may also be used to predetermine specific cleavage sites in recombinant proteins with the aid of certain sequence regions that are recognized by signal peptidases. Proteins according to the invention can thus be activated and/or deactivated in vitro. The scope of protection of the present invention encompasses each of these proteins providing it fails
® ® WO 02/10356 22 PCT/EP01/08359 ] within the claimed scope of protection and imparts amylolytic activity.
Chimeral or hybrid proteins according to the invention are understood to be proteins which are made up of elements emanating naturally from various polypeptide chains. This procedure is also known as shuffling or fusion mutagenesis. Proteins are chimeral proteins according to the invention when the proteins obtained by fusion have amylolytic activity in the broadest sense. This may be developed or modified by a part of the molecule which derives from a protein according to the invention and lies within the claimed similarity range. The object of such a fusion can be, for example, to produce or modify an amylolytic function or a function supporting the hydrolysis of a-1,4-glycosidic bonds with the aid of the fused-on part of the protein according to the invention. In the context of the invention, it does not matter whether such a chimeral protein consists of a single polypeptide chain or of several subunits among which various functions can be distributed. In order to realize the second alternative, it is possible, for example, to split a single chimeral polypeptide chain into several by controlled proteolytic cleavage either post-translationally or after a purification step. The present invention also relates to chimeral proteins which, by virtue of their construction, have an optionally lower identity over their entire amino acid and/or nucleotide sequence than defined above for the similarity range according to the invention, but may be assigned to it in at least one of the regions introduced by fusion and perform the same functions in this part as in an amylase which falls within the above- mentioned homology range over its entire length.
Proteins according to the invention obtainable by insertion mutation are variants of the proteins which fall over their entire sequence length into the designated range of protection of the SEQ ID NO. 1 or SEQ ID NO. 2 sequences and which have been obtained by insertion of a nucleic acid or protein fragment into the respective sequences. As with hybrid formation, the object of insertion mutagenesis can be to combine individual properties
® @® WO 02/10356 23 PCT/EP01/08359 of proteins according to the invention with those of other proteins. Proteins are proteins according to the invention obtained by insertion mutation or chimeral proteins when the regions to be attributed through their homology to the SEQ ID NO. 1 or SEQ ID NO. 2 sequences have corresponding homology values and the protein has an amylolytic function in the broadest . sense by virtue of those regions.
Accordingly, proteins obtained by inversion mutagenesis and those with a regrouping of various parts of the molecule which differs from the original amino acid sequence are included in the scope of protection of the present invention. It may be regarded as a deletion variant, an insertion variant or as a shuffling variant of the original protein.
Amylolytically active derivatives according to the invention are understood to be amylolytic proteins which have been modified, for example in connection with protein biosynthesis through processing by the host organism or chemically, for example by the transformation of a side chain of an amino acid or by covalent bonding of another compound to the protein. This compound may consist, for example, of other proteins which are bound to proteins according to the invention, for example by bifunctional chemical compounds. Such modifications can influence, for example, the substrate specificity or the strength of the bond to the substrate or can temporarily block the enzymatic activity where the coupled substance is an inhibitor. This may be appropriate, for example, for the duration of storage. Another embodiment are derivatives which have been obtained by covalent bonding to a macromolecular carrier such as, for example, polyethylene glycol or a polysaccharide.
Other solutions to the problem addressed by the invention are amylolytic proteins or derivatives which have at least one antigenic determinant in common with one of the above-mentioned proteins or derivatives.
This is because the development of enzymatic activities is critically
@® WO 02/10356 24 PCT/EP01/08359 ] determined not just by the pure amino acid sequence of a protein, but also by its secondary structural elements and its three-dimensional folding.
Thus, domains differing clearly from one another in their primary structure can form spatially substantially corresponding structures and can thus provide for the same enzymatic behavior. Such common features in the secondary structure are normally recognized as corresponding antigenic determinants of antisera or pure or monoclonal antibodies. Structurally similar proteins or derivatives can therefore be detected and assigned through immunochemical cross reactions.
Accordingly, the scope of protection of the present invention also encompasses proteins or derivatives which have amylolytic activity and which can possibly be assigned to the above-defined proteins according to the invention or derivatives through their immunochemical relationship, but not through their homology values in the primary structure.
Proteins according to the invention which emanate from natural sources are preferred embodiments of the present invention, particularly where they originate from such microorganisms as single-cell fungi or bacteria. This is because such microorganisms are easier to handle than multicell organisms or cell cultures derived from them. These represent appropriate options for special embodiments.
Proteins or derivatives according to the invention from gram-positive bacteria are particularly preferred because they do not have an external membrane and therefore directly release secreted proteins into the surrounding medium.
Proteins or derivatives according to the invention from gram-positive bacteria of the genus Bacillus are most particularly preferred because they are established as production organisms with a particularly high production performance in industrial processes.
Of the proteins or derivatives according to the invention from
Bacillus species, those from alcaliphilic bacilli are preferred, those from
® ® WO 02/10356 25 PCT/EP01/08359
Bacillus sp. A 7-7 being particularly preferred and those from the strain
Bacillus sp. A 7-7 (DSM 12368) most particularly preferred. This is because the embodiment of the enzyme according to the invention of which the associated sequences are shown .in the sequence protocol and of which the enzymatic characteristics are described in the Examples was originally obtained from that strain.
Strains which release the amylolytic protein formed into the medium surrounding them are preferred for production reasons.
It is possible that, although naturally occurring producers can produce an amylolytic enzyme according to the invention, they only express it and/or release it into the surrounding medium to a minimal extent under the conditions initially determined. They still fall within the scope of protection of the present invention as long as it is possible experimentally to determine suitable environmental conditions or low molecular weight or other factors under whose influence they can be stimulated to produce the protein according to the invention on a level which makes economic utilization appear appropriate. A regulating mechanism such as this can be purposefully used for biotechnological production, for example for regulating the responsible promoters.
Depending on its isolation, working up or preparation, a protein can be associated with various other substances, particularly if it has been recovered from natural producers of the protein. Certain other substances may then — or even independently - have been purposefully added to it, for example to increase its stability in storage. Accordingly, the definition of the protein according to the invention also encompasses all preparations of the actual protein essential to the invention. This is also independent of whether or not it actually develops this enzymatic activity in a certain preparation because it can be desirable for the protein to have little or no activity in storage and only to develop its amylolytic activity at the time of use. This can depend, for example, on the folding status of the protein or
® WO 02/10356 26 PCT/EP01/08359 ) can result from the reversible binding of one or more companion substances from the preparation or from another control mechanism.
Proteins according to the invention, particularly in storage, can be protected by stabilizers, for example against denaturing, disintegration or inactivation, for example by physical influences, oxidation or proteolytic cleavage. In the case of proteins obtained from microorganisms, inhibition of proteolysis is particularly critical because most microorganisms secrete various proteases as digestive enzymes into the surrounding media. Such enzymes can seriously damage the interesting proteins during the subsequent purification steps.
One group of stabilizers are reversible protease inhibitors such as, for example, benzamidine hydrochloride and leupeptin, borax, boric acids, boron acids, salts or esters thereof, peptide aldehydes or pure peptidic inhibitors, such as ovomucoid or specific subtilisin inhibitors. Other common enzyme stabilizers are aminoalcohols, such as mono-, di-, tri- ethanolamine and —propanolamine, aliphatic carboxylic acids up to Cig, dicarboxylic acids, lower aliphatic alcohols, but above all polyols such as, for example, glycerol, ethylene glycol, propylene glycol or sorbitol. Calcium salts such as, for example, calcium acetate or calcium formate, magnesium salts, various polymers, such as for example lignin, cellulose ethers, polyamides or water-soluble vinyl copolymers, are also used to stabilize the enzyme preparation, above all against physical influences or pH variations.
Reducing agents and antioxidants, such as sodium sulfite or reducing sugars for example, increase the stability of the proteins against oxidative disintegration.
The present invention is also embodied in corresponding nucleic acids providing the nucleic acids in question code for an amylolytic protein in the broadest sense and show sufficient similarity — as defined above — to the SEQ ID NO. 1 sequence, more particularly in nucleic acids which code for a protein that corresponds to the partial range of amino acids 32 to 516
@® @ 000356 27 PCT/EP01/08359 of the amino acid sequence shown in SEQ ID NO.1.
Particularly preferred embodiments are nucleic acids which code for one of the above-described amylolytic proteins according to the invention.
This also includes variants which do not fall within the similarity range defined in SEQ ID NO. 1 over their entire sequence length, but do so in individual regions. These include, for example, the nucleotide sequences which, as explained above, have been obtained by insertion or deletion mutation, chimeral proteins or protein fragments. However, so-called antisense constructs, for example through individual partial sections, also represent embodiments of the present invention because they can be used to regulate the amylolytic activity.
Nucleic acids form the starting point for molecular-biological investigations and further developments. Such methods are described, for example, in the manual by Fritsch, Sambrook and Maniatis “Molecular cloning: a laboratory manual”, Cold Spring Harbour Laboratory Press,
New York, 1989. All the genetic engineering and protein-biochemical methods which come under the heading of protein engineering in the prior art are also based on the gene, particularly the cloned gene. Proteins according to the invention can be further optimized for various uses by such methods, for example by point mutagenesis or by fusion with sequences from other genes.
The variants according to the invention of a protein obtainable by molecular-biological methods known per se include in particular those with individual, specific amino acid exchanges or randomized point mutations, deletions of individual amino acids or of partial sequences, fusions with other fragments or other enzymes, insertions or inversions, i.e. partial sequence inversions. Such mutations or modifications can represent preferred embodiments for specific applications. Such a mutagenesis can be carried out purposefully or by random methods. It can be combined, for example, with a subsequent activity-directed screening and selection
@® [ WO 02/10356 28 PCT/EP01/08359 } process on the cloned genes. The genes obtained by mutation fall within the scope of protection of the present invention providing they code for amylolytic proteins in the broadest sense and fall within the similarity range defined above, at least in the homologous and functionally relevant regions.
Another solution to the problem addressed by the invention and hence another embodiment of the invention are the organisms which naturally form a protein according to the invention or derivative or contain nucleic acids which code for a protein according to the invention or derivative. This is because their discovery enables the inventive concept to be put into practice. Such organisms are obtainable by generally known techniques, for example by isolating strains from a natural habitat or by screening of gene banks. The nucleotide sequence shown in SEQ ID NO.1 may be used, for example, as a screening probe or as an original for the construction of corresponding PCR primers. Analogously, short-chain or complete peptides with amino acid sequences according to SEQ ID NO. 2 may be used to form corresponding antisera with which corresponding organisms or the proteins released from them can be identified.
In accordance with the foregoing observations, microorganisms, preferably bacteria, especially gram-positive bacteria including those of the genus Bacillus, more particularly Bacillus sp. A 7-7 and most particularly
Bacillus sp. A 7- 7(DSM 12368), are preferred above all by virtue of their cultivatability.
Another embodiment of the invention are vectors which contain one of the nucleic acid regions of the second embodiment.
This is because, to use nucleic acids, the DNA is suitably cloned in a vector. Such vectors include, for example, those which are derived from bacterial plasmids, from viruses or from bacteriophages or predominantly synthetic vectors or plasmids with elements of various origins. With the other genetic elements present, vectors are able to establish themselves as stable units in the respective host cells over several generations. In the
® ® WO 02/10356 29 PCT/EP01/08359 context of the invention, it does not matter whether they establish themselves extrachromosomally as independent units or are integrated into a chromosome. Which of the many systems known from the prior art is selected will depend upon the particular individual case. Critical factors in this regard include, for example, the number of copies which can be made, the selection systems available, including above all resistances to antibiotics, and the cultivatability of the host cells capable of accommodating the vectors.
The vectors form suitable starting points for molecular-biological and biochemical investigations of the particular gene or associated protein and for further developments according to the invention and ultimately for the amplification and production of proteins according to the invention. They represent embodiments of the present invention insofar as the sequences of the nucleic acid regions according to the invention present lie within the homology range defined in detail in the foregoing.
Preferred embodiments of the present invention are cloning vectors.
Besides storage, biological amplification and selection of the interesting gene, cloning vectors are suitable for the characterization of the particular gene, for example through the drawing up of a restriction map or sequencing. Cloning vectors are also preferred embodiments of the present invention because they represent a transportable and storable form of the claimed DNA. They are also preferred starting points for molecular- biological techniques which are not restricted to cells, such as the polymerase chain reaction for example.
Expression vectors have partial sequences which are capable of replicating in the host organisms optimized for the production of proteins and of expressing the gene present in the host organism. Preferred embodiments are expression vectors which themselves carry the genetic elements necessary for expression. Expression is influenced, for example, by promoters which regulate the transcription of the gene. Thus,
® ® WO 02/10356 30 PCT/EP01/08359 expression can take place through the natural promoter originally located before the gene and also after genetically engineered fusion both through a promoter of the host cell provided on the expression vector and also through a modified promoter or a totally different promoter of another organism.
Preferred embodiments of the invention are expression vectors which can be regulated through changes in the culture conditions or by addition of certain compounds, such as for example the cell density or special factors. Expression vectors enable the associated protein to be heterologously produced, i.e. in an organism other than that from which it can naturally be obtained. Homologous protein production from a host organism naturally expressing the gene via a suitable vector also lies within the scope of protection of the present invention. This can have the advantage that natural modification reactions associated with the translation can be carried out as well on the protein formed as they would take place naturally.
Other embodiments of the present invention can be cell-free expression enzymes where protein biosynthesis is completed in vitro.
Expression systems such as these are also established in the prior art.
Another embodiment of the present invention are cells which contain one of the above-defined vectors, more particularly a cloning or expression vector. This is because, in the course of molecular-biological works as required, for example, for mutagenesis, sequencing or storage of the vectors, they are transformed into corresponding cells. Depending on the method, gram-positive bacteria for example, but especially gram-negative bacteria, can be suitable for this purpose.
Another embodiment are host cells which express a protein or derivative of the first embodiment or can be stimulated to express that protein or derivative, preferably using an expression vector of the type defined above.
® ® WO 02/10356 31 PCT/EP01/08359
This is because the preferred in vivo synthesis of an amylolytic enzyme according to the invention requires the transfer of the associated gene into a host cell. Suitable host cells are, in principle, any organisms, i.e. prokaryotes, eukaryotes or cyanophyta. Preferred host cells are those which are easy to handle genetically, for example as far as transformation with the expression vector and its stable establishment are concerned, for example single-cell fungi or bacteria. In addition, preferred host cells are distinguished by easy microbiological and biotechnological handling. This includes, for example, easy cultivation, high growth rates, minimal fermentation media requirements and good production and secretion rates for foreign proteins. The optimal expression systems for the particular individual case often have to be experimentally determined from the large number of different systems available in the prior art. In this way, each protein according to the invention can be obtained from a large number of host organisms.
Preferred embodiments are host cells which can be regulated in their activity through genetic regulation elements which are available, for example, on the expression vector but which can also be present from the outset in these cells. The host cells in question can be stimulated to express, for example by controlled addition of chemical compounds serving as activators, by changing the cultivation conditions or on reaching a certain cell density. This provides for very economical production of the interesting proteins.
A variant of this experimental principle are expression systems where additional genes, for example those made available on other vectors, influence the production of proteins according to the invention. They may be modifying gene products or those which are to be purified together with the protein according to the invention, for example to influence its amylolytic function. These may be, for example, other proteins or enzymes, inhibitors or elements which influence the interaction with various
® ® WO 02/10356 32 PCT/EPQ1/08359 } substrates.
Preferred host cells are prokaryotic or bacterial cells. Bacteria are generally distinguished from eucaryotes by shorter generation times and less demanding cultivation conditions. Inexpensive processes for the production of proteins according to the invention can thus be established.
Host cells and particularly bacteria which secrete the protein or derivative formed into the surrounding medium, so that the expressed proteins according to the invention can be directly purified, are particularly preferred.
One embodiment of the present invention uses Bacillus sp. A 7-7 (DSM 12368) itself for homologously expressing proteins according to the invention. This can be done, for example, via an introduced vector which introduces the already endogenously present gene or modifications thereof according to the invention into these cells, for example in a multiple number of copies. This can be particularly advantageous if, after its synthesis, the protein is to be subjected to modifications which are suitably carried out by the cells in question themselves.
By contrast, heterologous expression is preferred. Gram-positive bacteria, such as actinomycetes or bacilli for example, have no outer membrane so that they release secreted proteins directly into the medium surrounding them. Accordingly, bacteria preferred for heterologous expression include those of the genus Bacillus, more particularly those of the species Bacillus licheniformis, Bacillus amyloliquefaciens, Bacillus subtilis or Bacillus alcalophilus.
Gram-negative bacteria may also be used for heterologous expression. In their case, a large number of proteins are secreted into the periplasmatic space, i.e. into the compartment between the two membranes surrounding the cells. This can be advantageous for special applications. Gram-negative bacteria include, for example, those of the genus Kiebsiella or Escherichia, preferably the species Escherichia coil and
® ® WO 02/10356 33 PCT/EP01/08359 more preferably the strains E. coli JM 109, E. coli DH 100B or E. coli DH 12S.
Eukaryotic cells are also suitable for the production of amylolytic proteins according to the invention. Examples include yeasts, such as
Saccharomyces or Kluyveromyces. This can be particularly advantageous, for example, when the proteins are to be subjected in connection with their synthesis to modifications which such systems allow. These include, for example, the binding of low molecular weight compounds, such as membrane anchors or oligosaccharides.
All the elements discussed above may be combined into processes for producing proteins according to the invention. For each protein according to the invention, there are a number of possible combinations of process steps. They are all practical embodiments of the idea on which the present invention is based, namely quantitatively producing representatives of a protein type - defined through the amylolytic function and, at the same time, through the high homology to the sequences shown in the sequence protocols - with the aid of the associated genetic information. The optimal process has to be experimentally determined for each actual individual case.
In principle, the following procedure is adopted: nucleic acids according to the invention, i.e. those which fall within the above-defined similarity range to the SEQ ID NO. 1 sequence, are suitably ligated in the form of the DNA in a suitable expression vector. This is transformed into the host cell, for example into cells of an easy-to-cultivate bacterial strain, which releases the proteins, of which the genes are under the control of corresponding genetic elements, into the surrounding nutrient medium; regulating elements for this can be made available, for example, by the expression vector. The protein according to the invention can be purified from the surrounding medium by several purification steps such as, for example, precipitation or chromatography. The expert is able to scale up a
_ ® WO 02/10356 34 PCT/EP01/08359 } system that has been experimentally optimized in the laboratory to industrial-scale production.
The most important industrial applications for proteins according to the invention are listed in the following. Many established industrial applications for amylolytic enzymes are described in manuals, such as for example the book by H. Uhlig entitied “Industrial enzymes and their applications”, Wiley, New York, 1998. The following list is by no means complete and merely represents a selection of the many theoretically possible applications. If it should turn out that individual proteins according to the invention are suitable for additional applications not expressly claimed herein, those applications are hereby included in the scope of protection of the present invention.
An important application for amylolytic enzymes is their use as active components in detergents/cleaners for cleaning textiles or hard surfaces. In such applications, the amylolytic activity is used for hydrolytically dissolving carbohydrate-containing, more especially starch- like, soils and/or removing them from the substrate. To this end, the enzymes may be used on their own, in suitable media or even in detergents/cleaners. These compositions are distinguished by the fact that the amylolytic enzymes and the other components synergistically effect the elimination of the soils, for example by the hydrolysis products of the amylolytic proteins being solubilized by other ingredients of the compositions, such as surfactants for example. A protein according to the invention can be used both in compositions for institutional or industrial users and in products for the domestic consumer.
Accordingly, another embodiment of the invention are any detergents/cleaners which are characterized in that they contain an amylolytic protein according to the invention or derivative thereof.
By this is meant all possible types of cleaning compositions, both concentrates and compositions to be used without dilution; for use on a
® WO 02/10356 35 PCT/EP01/08359 commercial scale, in washing machines or in hand washing or cleaning.
Such compositions include, for example, detergents for textiles, carpets or natural fibers for which the term detergent is used in the present specification. They also include, for example detergents for dishwashers or manual dishwashing or cleaners for hard surfaces, such as metals, glass china, ceramic, tiles, stone, painted surfaces, plastics, wood or leather; for these, the term cleaner is used in the present specification. Any type of cleaning composition represents an embodiment of the present invention providing it is enriched by a protein according to the invention.
Embodiments of the present invention encompass all supply forms of the compositions according to the invention established in the prior art and/or all appropriate supply forms of the compositions according to the invention. These include, for example, solid, powder-form, liquid, gel-form or paste-form compositions, optionally consisting of several phases, compressed or non-compressed. The supply forms also include extrudates, granules, tablets and pouches packed both in large containers and in portions.
Besides an enzyme essential to the invention, the composition according to the invention optionally contains other ingredients, such as surfactants, for example nonionic, anionic and/or amphoteric surfactants, and/or bleaching agents and/or builders and optionally other typical ingredients.
Preferred nonionic surfactants are alkoxylated, advantageously ethoxylated, more particularly primary alcohols preferably containing 8 to 18 carbon atoms and an average of 1 to 12 mol ethylene oxide (EO) per mol alcohol, in which the alcohol residue may be linear or, preferably, 2- methyl-branched or may contain linear and methyl-branched residues in the form of the mixtures typically present in oxoalcohol residues. However, alcohol ethoxylates containing linear residues of alcohols of native origin with 12 to 18 carbon atoms, for example coconut oil alcohol, palm oil
® WO 02/10356 36 PCT/EP01/08359 ) alcohol, tallow alcohol or oleyl alcohol, and an average of 2 to 8 EO per mol alcohol are particularly preferred. Preferred ethoxylated alcohols include, for example, Ciz.14 alcohols containing 3 EO or 4 EO, Cg41 alcohol containing 7 EO, C43.15 alcohols containing 3 EO, 5 EO, 7 EO or 8 EO, Ciz2-18 alcohols containing 3 EO, 5 EO or 7 EO and mixtures thereof, such as mixtures of C42.44 alcohol containing 3 EO and Cs2.4g alcohol containing 5 EO. The degrees of ethoxylation mentioned are statistical mean values which, for a special product, may be either a whole number or a broken number. Preferred alcohol ethoxylates have a narrow homolog distribution (narrow range ethoxylates, NRE). In addition to these nonionic surfactants, fatty alcohols containing more than 12 EO may also be used. Examples of such fatty alcohols are tallow alcohols containing 14 EO, 25 EO, 30 EO or 40 EO.
Another class of preferred nonionic surfactants which are used either as sole nonionic surfactant or in combination with other nonionic surfactants are alkoxylated, preferably ethoxylated or ethoxylated and propoxylated, fatty acid alkyl esters preferably containing 1 to 4 carbon atoms in the alkyl chain, more particularly fatty acid methyl esters.
Another class of nonionic surfactants which may be used with advantage are the alkyl polyglycosides (APGs). Suitable alkyl polyglycosides correspond to the general formula RO(G), where R is a linear or branched, more particularly 2-methyl-branched, saturated or unsaturated aliphatic radical containing 8 to 22 and preferably 12 to 18 carbon atoms, G is a glycose unit containing 5 or 6 carbon atoms, preferably glucose. The degree of glycosidation z is between 1.0 and 4.0, preferably between 1.0 and 2.0 and more preferably between 1.1 and 1.4.
Linear alkyl polyglucosides, i.e. alkyl polyglycosides in which the polyglycosyl moiety is a glucose unit and the alkyl moiety is an n-alkyl group, are preferably used.
Nonionic surfactants of the amine oxide type, for example N-
® ® WO 02/10356 37 PCT/EP01/08359 cocoalkyl-N,N-dimethylamine oxide and N-tallowalkyl-N,N-dihydroxyethyl amine oxide, and the fatty acid alkanolamide type are also suitable. The quantity in which these nonionic surfactants are used is preferably no more, in particular no more than half, the quantity of ethoxylated fatty alcohols used.
Other suitable surfactants are polyhydroxyfatty acid amides cor- responding to formula (ll):
R’
R-CO-N-[Z] (1) in which RCO is an aliphatic acyl radical containing 6 to 22 carbon atoms,
R' is hydrogen, an alkyl or hydroxyalkyl radical containing 1 to 4 carbon atoms and [Z] is a linear or branched polyhydroxyalkyl radical containing 3 to 10 carbon atoms and 3 to 10 hydroxyl groups. The polyhydroxyfatty acid amides are known substances which may normally be obtained by reductive amination of a reducing sugar with ammonia, an alkylamine or an alkanolamine and subsequent acylation with a fatty acid, a fatty acid alkyl ester or a fatty acid chloride.
The group of polyhydroxyfatty acid amides also includes compounds corresponding to formula (111):
R'-0-R?
R-CO-N-[Z] (1) in which R is a linear or branched alkyl or alkenyl group containing 7 to 12 carbon atoms, R'is a linear, branched or cyclic alkyl group or an aryl group containing 2 to 8 carbon atoms and R? is a linear, branched or cyclic alkyl group or an ary! group or an oxyalkyl group containing 1 to 8 carbon atoms,
C14 alkyl or phenyl groups being preferred, and [Z] is a linear polyhydroxy- alkyl group, of which the alkyl chain is substituted by at least two hydroxyl
® ® WO 02/10356 38 PCT/EP01/08359 ] groups, or alkoxylated, preferably ethoxylated or propoxylated, derivatives of that group. [£] is preferably obtained by reductive amination of a reduced sugar, for example glucose, fructose, maltose, lactose, galactose, mannose or xylose. The N-alkoxy- or N-aryloxy-substituted compounds may then be converted into the required polyhydroxyfatty acid amides by, for example, reaction with fatty acid methyl esters in the presence of an alkoxide as catalyst.
Suitable anionic surfactants are, for example, those of the sulfonate and sulfate type. Suitable surfactants of the sulfonate type are preferably
Cg.13 alkyl benzenesulfonates, olefin sulfonates, i.e. mixtures of alkene and hydroxyalkane sulfonates, and the disulfonates obtained, for example, from
C12.18 monoolefins with an internal or terminal double bond by sulfonation with gaseous sulfur trioxide and subsequent alkaline or acidic hydrolysis of the sulfonation products. Other suitable surfactants of the sulfonate type are the alkane sulfonates obtained from Ci,.15 alkanes, for example by sulfochlorination or sulfoxidation and subsequent hydrolysis or neutralization. The esters of «-sulfofatty acids (ester sulfonates), for example the a-sulfonated methyl esters of hydrogenated coconut oil, palm kernel oil or tallow fatty acids, are also suitable.
Other suitable anionic surfactants are sulfonated fatty acid glycerol esters. Fatty acid glycerol esters in the context of the present invention are the monoesters, diesters and triesters and mixtures thereof which are obtained where production is carried out by esterification of a monoglycerol with 1 to 3 mol fatty acid or in the transesterification of triglycerides with 0.3 to 2 mol glycerol. Preferred sulfonated fatty acid glycerol esters are the sulfonation products of saturated fatty acids containing 6 to 22 carbon atoms, for example caproic acid, caprylic acid, capric acid, myristic acid, lauric acid, palmitic acid, stearic acid or behenic acid.
Preferred alk(en)yl sulfates are the alkali metal salts and, in
® WO 02/10356 39 PCT/EPQ01/08359 particular, the sodium salts of the sulfuric acid semiesters of Ci,.15 fatty alcohols, for example cocofatty alcohol, tallow fatty alcohol, lauryl, myristyl, cetyl or stearyl alcohol, or Cq.20 Oxoalcohols and the corresponding semiesters of secondary alcohols with the same chain length. Other preferred alk(en)yl sulfates are those with the chain length mentioned which contain a synthetic, linear alkyl chain based on a petrochemical and which are similar in their degradation behavior to the corresponding compounds based on oleochemical raw materials. Ci2.16 alkyl sulfates,
C12-15 alkyl sulfates and Ci4.15 alkyl sulfates are preferred from the point of view of washing technology. Other suitable anionic surfactants are 2,3- alkyl sulfates.
The sulfuric acid monoesters of linear or branched C;.,¢ alcohols ethoxylated with 1 to 6 mol ethylene oxide, such as 2-methyl-branched
Co-11 alcohols containing on average 3.5 mol ethylene oxide (EQ) or Cqz.18 fatty alcohols containing 1 to 4 EO, are also suitable. In view of their high foaming capacity, they are only used in relatively small quantities, for example in quantities of 1 to 5% by weight, in cleaners.
Other suitable anionic surfactants are the salts of alkyl sulfosuccinic acid which are also known as sulfosuccinates or as sulfosuccinic acid esters and which represent monoesters and/or diesters of sulfosuccinic acid with alcohols, preferably fatty alcohols and, more particularly, ethoxylated fatty alcohols. Preferred sulfosuccinates contain Cg g fatty alcohol residues or mixtures thereof. Particularly preferred sulfosuccinates contain a fatty alcohol moiety derived from ethoxylated fatty alcohols which, considered in isolation, represent nonionic surfactants (for a description, see below). Of these sulfosuccinates, those of which the fatty alcohol moieties are derived from narrow-range ethoxylated fatty alcohols are particularly preferred. Alk(en)yl succinic acid preferably containing 8 to 18 carbon atoms in the alk(en)y! chain or salts thereof may also be used.
Other suitable anionic surfactants are, in particular, soaps. Suitable
® [ WO 02/10356 40 PCT/EP01/08359 soaps are saturated fatty acid soaps, such as the salts of lauric acid, myristic acid, palmitic acid, stearic acid, hydrogenated erucic acid and behenic acid, and soap mixtures derived in particular from natural fatty acids, for example coconut oil, palm kernel oil or tallow fatty acids.
The anionic surfactants, including the soaps, may be present in the form of their sodium, potassium or ammonium salts and as soluble salts of organic bases, such as mono-, di- or triethanolamine. The anionic surfactants are preferably present in the form of their sodium or potassium salts and, more preferably, in the form of their sodium salts.
The surfactants may be present in the detergents according to the invention in a total quantity of preferably 5% by weight to 50% by weight and more particularly 8% by weight to 30% by weight, based on the final detergent.
Bleaching agents may be present in accordance with the invention.
Among the compounds yielding H,O; in water which serve as bleaching agents, sodium percarbonate, sodium perborate tetrahydrate and sodium perborate monohydrate and are particularly important. Other useful bleaching agents are, for example, peroxopyrophosphates, citrate perhy- drates and H,O,-yielding peracidic salts or peracids, such as persulfates or persulfuric acid. The urea peroxohydrate percarbamide, which may be described by the formula H,N—CO-—NH;'H,O,, may also be used. |f desired, the compositions may also contain bleaching agents from the group of organic bleaches, particularly where they are used for cleaning hard surfaces, for example in dishwashing machines, although in principle organic bleaches may also be used in laundry detergents. Typical organic bleaching agents are diacyl peroxides, such as dibenzoyl peroxide for example. Other typical organic bleaching agents are the peroxy acids, of which alkyl peroxy acids and aryl peroxy acids are particularly mentioned as examples. Preferred representatives are peroxybenzoic acid and ring- substituted derivatives thereof, such as alkyl peroxybenzoic acids, but also
® WO 02/10356 41 PCT/EP0O1/08359 peroxy-a-naphthoic acid and magnesium monoperphthalate, aliphatic or substituted aliphatic peroxy acids, such as peroxylauric acid, peroxystearic acid, e-phthalimidoperoxycaproic acid [phthaloiminoperoxyhexanoic acid (PAP)], o-carboxybenzamidoperoxycaproic acid, N-nonenylamidoperadipic acid and N-nonenylamidopersuccinates and aliphatic and araliphatic peroxydicarboxylic acids, such as 1,12-diperoxycarboxylic acid, 1,9- diperoxyazelaic acid, diperoxysebacic acid, diperoxybrassylic acid, diperoxyphthalic acids, 2-decyldiperoxybutane-1,4-dioic acid, N,N- terephthaloyl-di(6-aminopercaproic acid).
The content of bleaching agents can be from 1 to 40% by weight and, in a particular embodiment, is from 10 to 20% by weight, perborate monohydrate or percarbonate advantageously being used. A synergistic use of amylase with percarbonate or amylase with percarboxylic acid is disclosed in WO 99/63036 and WO 99/63037.
In order to obtain an improved bleaching effect where washing is carried out at temperatures of 60°C or lower and particularly in the pretreatment of laundry, the compositions may also contain bleach activators. Suitable bleach activators are compounds which form aliphatic peroxocarboxylic acids containing preferably 1 to 10 carbon atoms and more preferably 2 to 4 carbon atoms and/or optionally substituted perbenzoic acid under perhydrolysis conditions. Substances bearing O- and/or N-acyl groups with the number of carbon atoms mentioned and/or optionally substituted benzoyl groups are suitable. Preferred bleach activators are polyacylated alkylenediamines, more particularly tetraacetyl ethylenediamine (TAED), acylated triazine derivatives, more particularly 1,5-diacetyl-2,4-dioxohexahydro-1,3,5-triazine (DADHT), acylated glycol- urils, more particularly 1,3,4,6-tetraacety! glycolurit (TAGU), N-acylimides, more particularly N-nonanoyl succinimide (NOSI), acylated phenol sulfonates, more particularly n-nonanoyl or isononanoyloxybenzene- sulfonate (n- or iso-NOBS), acylated hydrocarboxylic acids, such as
® ® WO 02/10356 42 PCT/EP01/08359 ] triethyl-O-acetyl citrate (TEOC), carboxylic anhydrides, more particularly phthalic anhydride, isatoic anhydride and/or succinic anhydride, carboxylic acid amides, such as N-methyl diacetamide, glycolide, acylated polyhydric alcohols, more particularly triacetin, ethylene glycol diacetate, isopropenyl acetate, 2,5-diacetoxy-2,5-dihydrofuran and the enol esters known from
German patent applications DE 196 16 693 and DE 196 16 767, acetylated sorbitol and mannitol and the mixtures thereof (SORMAN) described in
European patent application EP 0 525 239, acylated sugar derivatives, more particularly pentaacetyl glucose (PAG), pentaacetyl fructose, tetraacetyl xylose and octaacetyl lactose, and acetylated, optionally N- alkylated glucamine and gluconolactone, triazole or triazole derivatives and/or particulate caprolactams and/or caprolactam derivatives, preferably
N-acylated lactams, for example N-benzoyl caprolactam and N-acetyl caprolactam, which are known from International patent applications WO- A-94/27970, WO-A-94/28102, WO-A-94/28103, WO-A-95/00626, WO-A- 95/14759 and WO-A-95/17498. The substituted hydrophilic acyl acetals known from German patent application DE-A-196 16 769 and the acyl lactams described in German patent application DE-A-196 16 770 and in
International patent application WO-A-95/14075 are also preferably used.
The combinations of conventional bleach activators known from German patent application DE-A-44 43 177 may also be used. Nitrile derivatives, such as cyanopyridines, nitrile quats, for example N-alkyl ammonium acetonitriles, and/or cyanamide derivatives may also be used. Preferred bleach activators are sodium-4-(octanoyloxy)-benzene sulfonate, n- nonanoyl or isononanoyloxybenzenesulfonate (n- or iso-NOBS), undecenoyloxybenzenesulfonate (UDOBS), sodium dodecanoyl- oxybenzenesulfonate (DOBS), decanoyloxybenzoic acid (DOBA, OBC 10) and/or dodecanoyloxybenzenesulfonate (OBS 12) and N-methyl morpholiium acetonitrile (MMA). Bleach activators such as these are present in the usual quantities of 0.01 to 20% by weight, preferably in
® [ WO 02/10356 43 PCT/EPO1/08359 quantities of 0.1% by weight to 15% by weight and more preferably in quantities of 1% by weight to 10% by weight, based on the composition as a whole.
In addition to or instead of the conventional bleach activators mentioned above, so-called bleach catalysts may also be incorporated.
Bleach catalysts are bleach-boosting transition metal salts or transition metal complexes such as, for example, manganese-, iron-, cobalt-, ruthenium- or molybdenum-salen complexes or carbonyl complexes.
Manganese, iron, cobalt, ruthenium, molybdenum, titanium, vanadium and copper complexes with nitrogen-containing tripod ligands and cobalt-, iron-, copper- and ruthenium-ammine complexes may also be used as bleach catalysts, the compounds described in DE 197 09 284 A1 preferably being used. According to WO 99/63038, acetonitrile derivatives and, according to
WO 99/63041, bleach-activating transition metal compounds are also capable of developing a bleach-activating effect in combination with amylases.
Compositions according to the invention generally contain one or more builders, more particularly zeolites, silicates, carbonates, organic co- buildes and - providing there are no objections to their use on ecological grounds - the phosphates. Phosphates are particularly preferred builders in dishwasher detergents.
Suitable crystalline layered sodium silicates correspond to the general formula NaMSixOxx+1 - Y H20, where M is sodium or hydrogen, x is a number of 1.6 to 4 and y is a number of 0 to 20, preferred values for x being 2, 3 or 4. Crystalline layered silicates such as these are described, for example, in European patent application EP-A-0 164 514. Preferred crystalline layered silicates corresponding to the above formula are those in which M is sodium and x assumes the value 2 or 3. Both B- and §-sodium disilicates NaySi,Os -y HO are particularly preferred. Such compounds are commercially available, for example, as SKS® (Clariant). Thus SKS-
@® @® ooiosss 44 PCT/EP01/08359 6® is mainly a 5-sodium disilicate with the formula Na;Si;Os - y H20 while
SKS-7® is mainly the B-sodium disilicate. By reaction with acids (for example citric acid or carbonic acid), the 6-sodium disilicate gives kanemite
NaHSi,Os - H,O which is marketed as SKS-9® and SKS-10® (Clariant). It can also be of advantage to use chemical modifications of these layered silicates. For example, the alkalinity of the layered silicates can be suitab ly influenced. Compared with the &-sodium disilicate, phosphate- or carbonate-doped layered silicates have modified crystal morphologies, dissolve more quickly and show increased an calcium binding capacity in relation to 8-sodium disilicate. Layered silicates with the general empirical formula x NaO - y HO - z P,0s, in which the ratio of x to y corresponds to a number of 0.35 to 0.6, the ratio of x to z corresponds to a number of 1.75 to 1200 and the ratio of y to z corresponds to a number of 4 to 2,800, are described in patent application DE 19601063. The solubility of the layered silicates can also be increased by using particularly fine-particle layered silicates. Compounds of the crystalline layered silicates with other ingredients may also be used. Particular mention is made of compounds with cellulose derivatives, which have advantages in the disintegrating effect and are used in particular in detergent tablets, and compounds with polycarboxylates, for example citric acid, or polymeric polycarboxylates, for example copolymers of acrylic acid.
Other useful builders are amorphous sodium silicates with a modulus (NaO:SiO, ratio) of 1:2 to 1:3.3, preferably 1:2 to 1:2.8 and more preferably 1:2 to 1:2.6 which dissolve with delay and exhibit multiple wash cycle properties. The delay in dissolution in relation to conventional amorphous sodium silicates can have been obtained in various ways, for example by surface treatment, compounding/compacting or by overdrying.
In the context of the invention, the term "amorphous" is also understood to encompass "X-ray amorphous". In other words, the silicates do not produce any of the sharp X-ray reflexes typical of crystalline substances in
® ® WO 02/10356 45 PCT/EP01/08359
X-ray diffraction experiments, but at best one or more maxima of the scattered X-radiation which have a width of several degrees of the diffraction angle. However, particularly good builder properties may even be achieved where the silicate particles produce crooked or even sharp diffraction maxima in electron diffraction experiments. This may be interpreted to mean that the products have microcrystalline regions between 10 and a few hundred nm in size, values of up to at most 50 nm and, more particularly, up to at most 20 nm being preferred. Compacted amorphous silicates, compounded amorphous silicates and overdried X- ray-amorphous silicates are particularly preferred.
The finely crystalline, synthetic zeolite containing bound water used in accordance with the invention is preferably zeolite A and/or zeolite P.
Zeolite MAP® (Crosfield) is a particularly preferred P-type zeolite.
However, zeolite X and mixtures of A, X and/or P are also suitable.
According to the invention, it is preferred to use, for example, a commercially obtainable co-crystallizate of zeolite X and zeolite A (ca. 80% by weight zeolite X) which is marketed by CONDEA Augusta S.p.A. under the name of VEGOBOND AX® and which may be described by the following formula: nNa,O - (1-n)K20 - Al,03 - (2 — 2.5)SiO; - (3.5 — 5.5) H20.
Suitable zeolites have a mean particle size of less than 10 um (volume distribution, as measured by the Coulter Counter Method) and contain preferably 18 to 22% by weight and more preferably 20 to 22% by weight of bound water.
The generally known phosphates may of course also be used as builders providing their use should not be avoided on ecological grounds.
Among the large number of commercially available phosphates, alkali metal phosphates have the greatest importance in the detergent industry,
® ® WO 02/10356 46 PCT/EP01/08359 } pentasodium triphosphate and pentapotassium triphosphate (sodium and potassium tripolyphosphate) being particularly preferred. “Alkali metal phosphates” is the collective term for the alkali metal (more particularly sodium and potassium) salts of the various phosphoric acids, including metaphosphoric acids (HPO3), and orthophosphoric acid (H3PO4) and representatives of higher molecular weight. The phosphates combine several advantages: they act as alkalinity sources, prevent lime deposits on machine parts and lime incrustations in fabrics and, in addition, contribute towards the cleaning effect.
Sodium dihydrogen phosphate (NaH;PO,) exists as the dihydrate (density 1.91 gcm™, melting point 60°) and as the monohydrate (density 2.04 gem). Both salts are white readily water-soluble powders which, on heating, lose the water of crystallization and, at 200°C, are converted into the weakly acidic diphosphate (disodium hydrogen diphosphate,
NasH.P-0;) and, at higher temperatures, into sodium trimetaphosphate (NasP30g) and Maddrell's salt (see below). NaHPOs shows an acidic reaction. It is formed by adjusting phosphoric acid with sodium hydroxide to a pH value of 4.5 and spraying the resulting "mash". Potassium dihydrogen phosphate (primary or monobasic potassium phosphate, potassium biphosphate, KDP), KH,PO4, is a white salt with a density of 2.33 gcm®, has a melting point of 253° [decomposition with formation of potassium polyphosphate (KPO3),] and is readily soluble in water.
Disodium hydrogen phosphate (secondary sodium phosphate),
Na,HPQ,, is a colorless, readily water-soluble crystalline salt. It exists in water-free form and with 2 mol (density 2.066 gcm™, water loss at 95°), 7 mol (density 1.68 gcm™, melting point 48° with loss of 5 H,0) and 12 mol of water (density 1.52 gcm™, melting point 35° with loss of 5 HO), becomes water-free at 100° and, on fairly intensive heating, is converted into the diphosphate Na,P,0;. Disodium hydrogen phosphate is prepared by neutralization of phosphoric acid with soda solution using phenolphthalein
® ® WO 02/10356 47 PCT/EP01/08359 as indicator. Dipotassium hydrogen phosphate (secondary or dibasic potassium phosphate), K;HPO,, is an amorphous white salt which is readily soluble in water.
Trisodium phosphate, tertiary sodium phosphate, NasPQO4, consists of colorless crystals which have a density of 1.62 gcm™ and a melting point of 73-76°C (decomposition) as the dodecahydrate, a melting point of 100°C as the decahydrate (corresponding to 19-20% P,0s) and a density of 2.536 gem? in water-free form (corresponding to 39-40% P,0s). Trisodium phosphate is readily soluble in water through an alkaline reaction and is prepared by concentrating a solution of exactly 1 mole of disodium phosphate and 1 mole of NaOH by evaporation. Tripotassium phosphate (tertiary or tribasic potassium phosphate), KsPOy, is a white deliquescent granular powder with a density of 2.56 gcm™, has a melting point of 1340° and is readily soluble in water through an alkaline reaction. It is formed, for example, when Thomas slag is heated with coal and potassium sulfate.
Despite their higher price, the more readily soluble and therefore highly effective potassium phosphates are often preferred to corresponding sodium compounds in the detergent industry.
Tetrasodium diphosphate (sodium pyrophosphate), NasP.0, exists in water-free form (density 2.534 gcm™, melting point 988°, a figure of 880° has also been mentioned) and as the decahydrate (density 1.815 - 1.836 gcm’3, melting point 94° with loss of water). Both substances are colorless crystals which dissolve in water through an alkaline reaction. NasP,O7 is formed when disodium phosphate is heated to >200° or by reacting phosphoric acid with soda in a stoichiometric ratio and spray-drying the solution. The decahydrate complexes heavy metal salts and hardness salts and, hence, reduces the hardness of water. Potassium diphosphate (potassium pyrophosphate), K4sP,07, exists in the form of the trihydrate and is a colorless hygroscopic powder with a density of 2.33 gcm™ which is soluble in water, the pH value of a 1% solution at 25° being 10.4.
® WO 02/10356 48 PCT/EP0O1/08359 )
Relatively high molecular weight sodium and potassium phosphates are formed by condensation of NaH,PO4 or KH,PO4. They may be divided into cyclic types, namely the sodium and potassium metaphosphates, and chain types, the sodium and potassium polyphosphates. The chain types in particular are known by various different names: fused or calcined phosphates, Graham's salt, Kurrol's salt and Maddrell's salt. All higher sodium and potassium phosphates are known collectively as condensed phosphates.
The industrially important pentasodium triphosphate, NasP3O1o (sodium tripolyphosphate), is a non-hygroscopic white water-soluble salt which crystallizes without water or with 6 H,O and which has the general formula NaO-[P(O)(ONa)-O].-Na where n = 3. Around 17 g of the salt free from water of crystallization dissolve in 100 g of water at room temperature, around 20 g at 60° and around 32 g at 100°. After heating of the solution for 2 hours to 100°, around 8% orthophosphate and 15% diphosphate are formed by hydrolysis. In the preparation of pentasodium triphosphate, phosphoric acid is reacted with soda solution or sodium hydroxide in a stoichiometric ratio and the solution is spray-dried. Similarly to Graham's salt and sodium diphosphate, pentasodium triphosphate dissolves many insoluble metal compounds (including lime soaps, etc.). Pentapotassium triphosphate, KsP3049 (potassium tripolyphosphate), is marketed for example in the form of a 50% by weight solution (> 23% P20s, 25% KO).
The potassium polyphosphates are widely used in the detergent industry.
Sodium potassium tripolyphosphates, which may also be used in accordance with the invention, also exist. They are formed for example when sodium trimetaphosphate is hydrolyzed with KOH: (NaPQj3)3 + 2 KOH — NazK,P3010 + HO
According to the invention, they may be used in exactly the same
® ® WO 02/10356 49 PCT/EP01/08359 way as sodium tripolyphosphate, potassium tripolyphosphate or mixtures thereof. Mixtures of sodium tripolyphosphate and sodium potassium tripolyphosphate or mixtures of potassium tripolyphosphate and sodium potassium tripolyphosphate or mixtures of sodium tripolyphosphate and potassium tripolyphosphate and sodium potassium tripolyphosphate may also be used in accordance with the invention.
Organic cobuilders which may be used in the detergents/cleaners according to the invention include, in particular, polycarboxylates or poly- carboxylic acids, polymeric polycarboxylates, polyaspartic acid, polyacetals, optionally oxidized dextrins, other organic cobuilders (see below) and phosphonates. These classes of substances are described in the following.
Useful organic builders are, for example, the polycarboxylic acids usable in the form of their sodium salts, polycarboxylic acids in this context being understood to be carboxylic acids which carry more than one acid function. These include, for example, citric acid, adipic acid, succinic acid, glutaric acid, malic acid, tartaric acid, maleic acid, fumaric acid, sugar acids, aminocarboxylic acids, nitrilotriacetic acid (NTA), providing its use is not ecologically unsafe, and mixtures thereof. Preferred salts are the salts of the polycarboxylic acids, such as citric acid, adipic acid, succinic acid, glutaric acid, tartaric acid, sugar acids and mixtures thereof.
The acids per se may also be used. Besides their building effect, the acids also typically have the property of an acidifying component and, hence, also serve to establish a relatively low and mild pH value in detergents or cleaners unless the pH value obtained by mixing of the other components is required. System-compatible and environmentally safe acids, such as citric acid, acetic acid, tartaric, maleic acid, lactic acid, glycolic acid, succinic acid, glutaric acid, adipic acid, gluconic acid and mixtures thereof, are particularly mentioned in this regard. However, mineral acids, particularly sulfuric acid, or bases, particularly ammonium or
® ® WO 02/10356 50 PCT/EP01/08359 alkali metal hydroxides, may also be used as pH adjusters. Such adjusters are present in the compositions according to the invention in quantities of not more than 20% by weight and more particularly in quantities of 1.2% by weight to 17% by weight.
Other suitable builders are polymeric polycarboxylates, i.e. for example the alkali metal salts of polyacrylic or polymethacrylic acid, for example those with a relative molecular weight of 500 to 70,000 g/mol.
The molecular weights mentioned in this specification for polymeric polycarboxylates are weight-average molecular weights M,, of the particular acid form which, basically, were determined by gel permeation chromatography (GPC) using a UV detector. The measurement was carried out against an external polyacrylic acid standard which provides realistic molecular weight values by virtue of its structural similarity to the polymers investigated. These values differ distinctly from the molecular weights measured against polystyrene sulfonic acids as standard. The molecular weights measured against polystyrene sulfonic acids are generally higher than the molecular weights mentioned in this specification.
Particularly suitable polymers are polyacrylates which preferably have a molecular weight of 2,000 to 20,000 g/mol. By virtue of their superior solubility, preferred representatives of this group are the short- chain polyacrylates which have molecular weights of 2,000 to 10,000 g/mol and, more particularly, 3,000 to 5,000 g/mol.
Also suitable are copolymeric polycarboxylates, particularly those of acrylic acid with methacrylic acid and those of acrylic acid or methacrylic acid with maleic acid. Acrylic acid/maleic acid copolymers containing 50 to 90% by weight of acrylic acid and 50 to 10% by weight of maleic acid have proved to be particularly suitable. Their relative molecular weights, based on the free acids, are generally in the range from 2,000 to 70,000 g/mol, preferably in the range from 20,000 to 50,000 g/mol and more preferably in the range from 30,000 to 40,000 g/mol. The (co)polymeric poly-
® ® WO 02/10356 51 PCT/EP01/08359 carboxylates may be used either in powder form or in the form of an aqueous solution. The content of (co)polymeric polycarboxylates in the detergents can be from 0.5 to 20% by weight and, more particularly, is from 1 to 10% by weight.
In order to improve solubility in water, the polymers may also contain allyl sulfonic acids such as, for example, allyloxybenzene sulfonic acid and methallyl sulfonic acid as monomer.
Other particularly preferred polymers are biodegradable polymers of more than two different monomer units, for example those which contain salts of acrylic acid and maleic acid and vinyl alcohol or vinyl alcohol derivatives as monomers or those which contain salts of acrylic acid and 2- alkylallyl sulfonic acid and sugar derivatives as monomers.
Other preferred copolymers are those which preferably contain acrolein and acrylic acid/acrylic acid salts or acrolein and vinyl acetate as monomers.
Other preferred builders are polymeric aminodicarboxylic acids, salts or precursors thereof. Polyaspartic acids or salts and derivatives thereof which have a bleach-stabilizing effect besides their cobuilder properties are particularly preferred.
Other suitable builders are polyacetals which may be obtained by reaction of dialdehydes with polyol carboxylic acids containing 5 to 7 carbon atoms and at least three hydroxyl groups. Preferred polyacetals are obtained from dialdehydes, such as glyoxal, glutaraldehyde, terephthal- aldehyde and mixtures thereof and from polyol carboxylic acids, such as gluconic acid and/or glucoheptonic acid.
Other suitable organic builders are dextrins, for example oligomers or polymers of carbohydrates which may be obtained by partial hydrolysis of starches. The hydrolysis may be carried out by standard methods, for example acid- or enzyme-catalyzed methods. The end products are preferably hydrolysis products with average molecular weights of 400 to
® ® WO 02/10356 52 PCT/EP01/08359 } 500,000 g/mol. A polysaccharide with a dextrose equivalent (DE) of 0.5 to 40 and, more particularly, 2 to 30 is preferred, the DE being an accepted measure of the reducing effect of a polysaccharide by comparison with dextrose which has a DE of 100. Both maltodextrins with a DE of 3 to 20 and dry glucose sirups with a DE of 20 to 37 and also so-called yellow dextrins and white dextrins with relatively high molecular weights of 2,000 to 30,000 g/mol may be used.
The oxidized derivatives of such dextrins are their reaction products with oxidizing agents which are capable of oxidizing at least one alcohol function of the saccharide ring to the carboxylic acid function. Particularly preferred organic builders for compositions according to the invention are oxidized starches or derivatives thereof according to EP 472 042, WO 97/25399 and EP 755 944. : Other suitable co-builders are oxydisuccinates and other derivatives of disuccinates, preferably ethylenediamine disuccinate. Ethylenediamine-
N,N’-disuccinate (EDDS) is preferably used in the form of its sodium or magnesium salts. Glycerol disuccinates and glycerol trisuccinates are also preferred in this connection. The quantities used in zeolite-containing and/or silicate-containing formulations are from 3 to 15% by weight.
Other useful organic co-builders are, for example, acetylated hydroxycarboxylic acids and salts thereof which may optionally be present in lactone form and which contain at least 4 carbon atoms, at least one hydroxy group and at most two acid groups.
Another class of substances with co-builder properties are the phosphonates, more particularly hydroxyalkane and aminoalkane phos- phonates. Among the hydroxyalkane phosphonates, 1-hydroxyethane-1,1- diphosphonate (HEDP) is particularly important as a co-builder. It is preferably used in the form of the sodium salt, the disodium salt showing a neutral reaction and the tetrasodium salt an alkaline reaction (pH 9).
Preferred aminoalkane phosphonates are ethylenediamine tetramethylene
_ ® WO 02/10356 53 PCT/EP01/08359 phosphonate (EDTMP), diethylenetriamine pentamethylenephosphonate (DTPMP) and higher homologs thereof. They are preferably used in the form of the neutrally reacting sodium salts, for example as the hexasodium salt of EDTMP or as the hepta- and octasodium salts of DTPMP. Of the phosphonates, HEDP is preferably used as a builder. In addition, the aminoalkane phosphonates have a pronounced heavy metal binding capacity. Accordingly, it can be of advantage, particularly where the foams also contain bleach, to use aminoalkane phosphonates, more particularly
DTPMP, or mixtures of the phosphonates mentioned. in addition, any compounds capable of forming complexes with alkaline earth metal ions may be used as co-builders.
The compositions according to the invention may optionally contain builders in quantities of up to 90% by weight and preferably in quantities of up to 75% by weight. Detergents according to the invention have builder contents of in particular 5% by weight to 50% by weight. In hard surface cleaners according to the invention, particularly dishwasher detergents, the builder content is in particular from 5% by weight to 88% by weight. In a preferred embodiment, such compositions are free from water-soluble builders. In another preferred embodiment, compositions according to the invention, particularly dishwasher detergents, contain 20% by weight to 40% by weight water-soluble organic builders, more particularly alkali metal citrate, 5% by weight to 15% by weight alkali metal carbonate and 20% by weight to 40% by weight alkali metal disilicate.
Solvents which may be used in the liquid or gel-form compositions of detergents/cleaners belong, for example, to the group of monohydric or polyhydric alcohols, alkanolamines or glycolethers providing they are miscible with water in the concentration range indicated. The solvents are preferably selected from ethanol, n- or i-propanol, butanols, ethylene glycol methyl ether, ethylene glycol ethyl ether, ethylene glycol propyl ether, ethylene glycol moo-n-butyl ether, diethylene glycol methyl ether,
® ® WO 02/10356 54 PCT/EPO1/08359 ) diethylene glycol diethyl ether, propylene glycol methyl, ethyl or propyl ether, dipropylene glycol monomethyl or monoethyl ether, diisopropylene glycol monomethyl or monoethyl ether, methoxy, ethoxy or butoxy triglycol, 1-butoxyethoxy-2-propanol, 3-methyl-3-methoxybutanol, propylene glycol t- butyl ether and mixtures of these solvents.
Solvents may be present in the liquid or gel-form detergents/cleaners according to the invention in quantities of 0.1 to 20% by weight, preferably in quantities below 15% by weight and more particularly in quantities below 10% by weight.
One or more thickeners, for example thickening systems, may be added to the composition according to the invention in order to adjust its viscosity. These high molecular weight substances, which are also known as swelling agents, generally absorb the liquids and swell in the process before finally changing into viscous, true or colloidal solutions.
Suitable thickeners are inorganic or polymeric organic compounds.
The inorganic thickeners include, for example, polysilicic acids, clay minerals, such as montmorillonites, zeolites, silicas and bentonites. The organic thickeners belong to the groups of natural polymers, modified natural polymers and fully synthetic polymers. Examples of naturally occurring polymers are agar agar, carrageen, tragacanth, gum arabic, alginates, pectins, polyoses, guar gum, locust bean gum, starch, dextrins, gelatin and casein. Modified natural substances which may be used as thickeners belong, above all, to the group of modified starches and celluloses and include, for example, carboxymethyl cellulose and other cellulose ethers, hydroxyethyl and hydroxypropyl cellulose and gum ethers.
Fully synthetic thickeners include polymers, such as polyacrylic and polymethacrylic compounds, vinyl polymers, polycarboxylic acids, polyethers, polyimines, polyamides and polyurethanes.
The thickeners may be used in a quantity of up to 5% by weight, preferably in a quantity of 0.05 to 2% by weight and more particularly in a
® @ WO 02/10356 95 PCT/EP01/08359 quantity of 0.1 to 1.5% by weight, based on the final composition.
The detergents/cleaners according to the invention may optionally contains sequestering agents, electrolytes and other auxiliaries, such as optical brighteners, redeposition inhibitors, silver corrosion inhibitors, dye transfer inhibitors, foam inhibitors, abrasives, dyes and/or perfumes, and microbial agents and/or UV absorbers as further ingredients.
Laundry detergents according to the invention may contain derivatives of diaminostilbenedisulfonic acid or alkali metal salts thereof as optical brighteners. Suitable optical brighteners are, for example, salts of 4,4'-bis-(2-anilino-4-morpholino-1,3,5-triazinyl-6-amino)-stilbene-2,2'- disulfonic acid or compounds of similar composition which contain a diethanolamino group, a methylamino group, an anilino group or a 2- methoxyethylamino group instead of the morpholino group. Brighteners of the substituted diphenyl styryl type, for example alkali metal salts of 4,4'- bis-(2-sulfostyryl)-diphenyl, 4,4'-bis-(4-chloro-3-sulfostyryl)-diphenyl or 4-(4- chlorostyryl)-4'-(2-sulfostyryl)-diphenyl, may also be present. Mixtures of the brighteners mentioned above may also be used.
The function of redeposition inhibitors is to keep the soil detached from the fibers suspended in the wash liquor. Suitable redeposition inhibitors are water-soluble, generally organic colloids, for example starch, glue, gelatin, salts of ether carboxylic acids or ether sulfonic acids of starch or cellulose or salts of acidic sulfuric acid esters of cellulose or starch.
Water-soluble polyamides containing acidic groups are also suitable for this purpose. Starch derivatives other than those mentioned above, for example aldehyde starches, etc., may also be used. Cellulose ethers, such as carboxymethyl cellulose (sodium salt), methyl cellulose, hydroxyalkyl cellulose, and mixed ethers, such as methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, methyl carboxymethyl cellulose and mixtures thereof, are preferably used, for example in quantities of 0.1 to 5% by weight, based on the composition.
® @® ooo 56 PCT/EP01/08359
In order to protect silverware against corrosion, silver corrosion inhibitors may be used in dishwashing detergents according to the invention. Silver corrosion inhibitors are known from the prior art and include, for example, benzotriazoles, iron(lll) chloride and CoSO4. As known from European patent EP 0 736 084 B1, for example, silver corrosion inhibitors particularly suitable for use together with enzymes are manganese, titanium, zirconium, hafnium, vanadium, cobalt or cerium salts and/or complexes in which the metals mentioned are present in one of the oxidation numbers Il, II, IV, V or VI. Examples of such compounds are MnSOQq, V20s, V204, VO,, TiIOSO,, K,TiFs, KoZrFe, Co(NO3)2, Co(NO3)s and mixtures thereof.
Soil release agents or soil repellents are generally polymers which, when used in a laundry detergent, provide the laundry fibers with soil- repelling properties and/or support the soil suspending capacity of the other ingredients of the detergent. A comparable effect can also be observed where they are used in hard surface cleaners.
Particularly effective and long-established soil release agents are copolyesters containing dicarboxylic acid, alklene glycol and polyalylene glycol units. Examples are copolymers or copolymers of polyethylene terephthalate and polyoxyethylene glycol (DT 16 17 141 or DT 22 00 911).
DE-OS 2253063 mentions acidic compositions containing inter alia a copolymer of a dibasic carboxylic acid and an alkylene or cycloalkylene polyglycol. Polymers of ethylene terephthalate and polyethylene oxide terephthalate and their use in detergents is described in DE-PS 28 57 292 and DE-PS 33 24 258 and in EP 0 253 567. European patent EP 066 944 relates to compositions containing a copolyester of ethylene glycol, polyethylene glycol, aromatic dicarboxylic acid and sulfonated aromatic dicarboxylic acid in certain molar ratios. European patent EP 0 185 427 describes methyl- or ethyl-terminated polyesters containing ethylene and/or propylene terephthalate units and polyethylene oxide terephthalate units
® ® WO 02/10356 57 PCT/EP01/08359 and detergents which contain such a soil-release polymer. European patent EP 0 241 984 relates to a polyester which, besides oxyethylene groups and terephthalic acid units, also contains substituted ethylene units and glycerol units. European patent EP 0 241 985 describes polyesters which, besides oxyethylene groups and terephthalic acid units, contain 1,2- propylene, 1,2-butylene and/or 3-methoxy-1,2-propylene groups and glycerol units and which are terminated by Ci4 alkyl groups. European patent application EP 0 272 033 describes at least partly C14 alkyl- or acyl- terminated polyesters containing polypropylene terephthalate and polyoxyethylene terephthalate units. European patent EP 0 274 907 describes sulfoethyl-terminated terephthalate-containing soil-release polyesters. According to European patent application EP 0 357 280, soil- release polyesters containing terephthalate, alkylene glycol and poly-Caz.4- glycol units are produced by sulfonation of unsaturated terminal groups.
International patent application WO 95/32232 relates to acidic aromatic soil-release polyesters. International patent application WO 97/31085 describes soil repellents for cotton fabrics which contain several functional units: a first unit, which may be cationic for example, is capable of adsorption onto the cotton surface by electrostatic interaction, and a second unit which is hydrophobic is responsible for the active substance remaining at the water/cotton interface.
Dye transfer inhibitors suitable for use in laundry detergents according to the invention include, in particular, polyvinyl pyrrolidones, polyvinyl imidazoles, polymeric N-oxides, such as poly-(vinylpyridine-N- oxide) and copolymers of vinyl pyrrolidone with viyl imidazole.
Where the compositions are used in machine cleaning processes, it can be of advantage to add typical foam inhibitors to them. Suitable foam inhibitors are, for example, soaps of natural or synthetic origin which have a high percentage content of Cis4 fatty acids. Suitable non-surface-active foam inhibitors are, for example, organopolysiloxanes and mixtures thereof
® ® WO 02/10356 58 PCT/EP01/08359 ] with microfine, optionally silanized, silica and also paraffins, waxes, microcrystalline waxes and mixtures thereof with silanized silica or bis- stearyl ethylenediamide. Mixtures of different foam inhibitors, for example mixtures of silicones, paraffins and waxes, may aiso be used with advantage. The foam inhibitors, more particularly silicone- and/or paraffin- containing foam inhibitors, are preferably fixed to a granular water-soluble or water-dispersible support. Mixtures of paraffins and bis-stearyl ethylenediamides are particularly preferred.
In addition, a hard surface cleaner according to the invention may contain abrasive constituents, more particularly from the group consisting of silica flours, wood flours, plastic powders, chalks and glass microbeads and mixtures thereof. Abrasives are present in the cleaners according to the invention is quantity of preferably not more than 20% by weight and more particularly in quantities of 5% to 15% by weight.
Dyes and perfumes are added to the detergents/cleaners according to the invention to improve the aesthetic impression created by the products and to provide the consumer not only with the required washing and cleaning performance but also with a visually and sensorially "typical and unmistakable" product. Suitable perfume oils or fragrances include individual perfume compounds, for example synthetic products of the ester, ether, aldehyde, ketone, alcohol and hydrocarbon type. Perfume compounds of the ester type are, for example, benzyl acetate, phenoxyethyl isobutyrate, p-tert.butyl cyclohexyl acetate, linalyl acetate, dimethyl benzyl carbinyl acetate, phenyl ethyl acetate, linalyl benzoate, benzyl formate, ethyl methyl phenyl glycinate, allyl cyclohexyl propionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether; the aldehydes include, for example, the linear alkanals containing 8 to 18 carbon atoms, citral, citronellal, citronellyl- oxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal; the ketones include, for example, the ionones, a-isomethyl
® ® WO 02/10356 59 PCT/EP01/08359 ionone and methyl cedryl ketone; the alcohols include anethol, citronellol, eugenol, geraniol, linalool, phenyl ethyl alcohol and terpineol and the hydrocarbons include, above all, the terpenes, such as limonene and pinene. However, mixtures of various perfumes which together produce an attractive perfume note are preferably used. Perfume oils such as these may also contain natural pefume mixtures obtainable from vegetable sources, for example pine, citrus, jasmine, patchouli, rose or ylang-ylang oil. Also suitable are clary oil, camomile oil, clove oil, melissa oil, mint oil, cinnamon leaf oil, lime blossom oil, juniper berry oil, vetiver oil, olibanum oil, galbanum oil and ladanum oil and orange blossom oil, neroli oil, orange peel oil and sandalwood oil. The dye content of detergents/cleaners is usually below 0.01% by weight while perfumes can make up as much as 2% by weight of the formulation as a whole.
The perfumes may be directly incorporated in the detergents/cleaners, although it can also be of advantage to apply the fragrances to supports which strengthen the adherence of the perfume to the articles being washed/cleaned and which provide treated textiles in particular with a long-lasting fragrance through a slower release of the perfume. Suitable support materials are, for example, cyclodextrins, the cyclodextrin/perfume complexes optionally being coated with other auxiliaries. Another preferred support for perfumes is the described zeolite
X which is also capable of absorbing perfumes instead of or in admixture with surfactants. Accordingly, detergents/cleaners containing the described zeolite X and perfumes preferably absorbed at least partly on the zeolite are preferred.
Preferred dyes which the expert will find no difficulty in selecting have high stability in storage, are unaffected by the other ingredients of the composition and by light and do not show pronounced substantivity towards textile fibers so as not to color them.
To control microorganisms, detergents/cleaners may contain
® ® WO 02/10356 60 PCT/EP01/08359 antimicrobial agents. Depending on the antimicrobial spectrum and the action mechanism, antimicrobial agents are classified as bacteriostatic agents and bactericides, fungistatic agents and fungicides, etc. Important representatives of these groups are, for example, benzalkonium chlorides, alkylaryl sulfonates, halophenols and phenol mercuriacetate. In the context of the teaching according to the invention, the expressions “antimicrobial activity” and “antimicrobial agent” have the usual meanings as defined, for example, by K.H. WallhduRer in " Praxis der Sterilisation, Desinfektion -
Konservierung : Keimidentifizierung - Betriebshygiene" (5th Edition, Stuttgart/New York: Thieme, 1995), any of the substances with antimicrobial activity described therein being usable. Suitable antimicrobial agents are preferably selected from the groups of alcohols, amines, aldehydes, antimicrobial acids and salts thereof, carboxylic acid esters, acid amides, phenols, phenol derivatives, diphenyls, diphenylalkanes, urea derivatives, oxygen and nitrogen acetals and formals, benzamidines, isothiazolines, phthalimide derivatives, pyridine derivatives, antimicrobial surface-active compounds, guanidines, antimicrobial amphoteric compounds, quinolines, 1,2-dibromo-2,4-dicyanobutane, iodo-2-propyl butyl carbamate, iodine, iodophores, peroxo compounds, halogen compounds and mixtures of the above.
The antimicrobial agent may be selected from ethanol, n-propanol, i- propanol, butane-1,3-diol, phenoxyethanol, 1,2-propylene glycol, glycerol, undecylenic acid, benzoic acid, salicylic acid, dihydracetic acid, o- phenylphenol, N-methyl morpholine acetonitrile (MMA), 2-benzyl-4- chlorophenol, 2,2'-methylene-bis-(6-bromo-4-chlorophenol), 4,4'-dichloro- 2'-hydroxydiphenyl ether (Dichlosan), 2,4,4'-trichloro-2'-hydroxydiphenyl ether (Trichlosan), chlorohexidine, N-(4-chlorophenyl)-N-3,4- dichlorophenyl)-urea, N,N'-(1,10-decanediyldi-1-pyridinyl-4-ylidene)-bis-(1- octanamine)-dihydrochloride, N,N'-bis-(4-chlorophenyt)-3,12-diimino- 2,4,11,13-tetraazatetradecane diimidoamide, glucoprotamines, antimicro-
® ® WO 02/10356 61 PCT/EP01/08359 bial surface-active quaternary compounds, guanidines, including the bi- and polyguanidines such as, for example, 1,6-bis-(2-ethylhexylbi- guanidohexane)-dihydrochloride, 1,6-di-(N1,N+'-phenyldiguanido-Ns,Ns')- hexane tetrahydrochloride, 1,6-di-(N1,N4-phenyl-N1,Ns-methyldiguanido-
Ns,Ns')-hexane dihydrochloride, 1,6-di-(N4,N{-o-chlorophenyldiguanido-
Ns,Ns')-hexane dihydrochloride, 1,6-di-(N4,N4'-2,6-dichlorophenyldiguanido-
Ns,Ns')-hexane dihydrochloride, 1,6-di-[N4N+'-B-(p-methoxyphenyl)-diguan- ido-Ns,Ns']-hexane dihydrochloride, 1,6-di-(N4N'-a-methyl-B-phenyldiguan- ido-Ns,Ns')-hexane dihydrochloride, 1,6-di-(N4,N'-p-nitrophenyldiguanido- Ns,Ns')-hexane dihydrochloride, ®:®-di-(N4,N4-phenyldiguanido-Ns,Ns')-di- n-propyl ether dihydrochloride, ®:w'-di-(N4,N4'-p-chlorophenyldiguanido-
Ns,Ns')-di-n-propyl ether tetrahydrochloride, 1,6-di-(N1,N4-2,4-dichloro- phenyldiguanido-Ns,Ns')-hexane tetrahydrochloride, 1,6-di-(N4,N4-p-methyl- phenyldiguanido-Ns,Ns')-hexanedihydrochloride, 1,6-di-(N1,N¢"-2,4,5-tri- chlorophenyldiguanido-Ns,Ns')-hexane tetrahydrochloride, 1,6-di-[N4,N1"-a- (p-chlorophenyl)-ethyldiguanido-Ns,Ns'l-hexane dihydrochloride, o:o-di- (N+,N+'-p-chlorophenyldiguanido-Ns,Ns')-m-xylene dihydrochloride, 1,12-di- (N1,N4'-p-chlorophenyldiguanido-Ns,Ns')-dodecane dihydrdochloride, 1,10- di-(N1,N¢'-phenyldiguanido-Ns,Ns')-decane tetrahydrochloride, 1,12-di- (N4,N+-phenyldiguanido-Ns,Ns')-dodecane tetrahydrochloride, 1,6-di- (N1,N4'-o-chlorophenyldiguanido-Ns,Ns')-hexane dihydrochloride, 1,6-di- (N1,N+'-o-chlorophenyldiguanido-Ns,Ns')-hexane tetrahydrochloride, ethylene-bis-(1-tolylbiguanide), ethylene-bis-(p-tolylbiguanide), ethylene- bis-(3,5-dimethylphenylbiguanide), ethylene-bis-(p-tert.amylphenyl- biguanide), ethylene-bis-(nonylphenylbiguanide), ethylene-bis-(phenyl- biguanide), ethylene-bis-(N-butylphenylbiguanide), ethylene-bis-(2,5- diethoxyphenylbiguanide), ethylene-bis-(2,4-dimethylphenylbiguanide), ethylene-bis-(o-diphenylbiguanide), ethylene-bis-(mixed-amylnaphthyl- biguanide), N-butylethylene-bis-(phenylbiguanide), trimethylene-bis-(o- tolylbiguanide), N-butyltrimethylene-bis-(phenylbiguanide) and the
® ® WO 02/10356 62 PCT/EP01/08359 corresponding salts, such as acetates, gluconates, hydrochlorides, hydrobromides, citrates, bisulifites, fluorides, polymaleates, N-cocoalkyl sarcosinates, phosphites, hypophosphites, perfluorooctanoates, silicates, sorbates, salicylates, maleates, tartrates, fumarates, ethylenediamine tetraacetates, iminodiacetates, cinnamates, thiocyanates, arginates, pyromellitates, tetracarboxybutyrates, benzoates, glutarates, monofluorophosphates, perfluoropropionates and mixtures thereof.
Halogenated xylene and cresol derivatives, such as p-chloro-m-cresol or p- chloro-m-xylene, and natural antimicrobial agents of vegetable origin (for example from spices or herbs), animal and microbial origin are also suitable. Preferred antimicrobial agents are antimicrobial surface-active quaternary compounds, a natural antimicrobial agent of vegetable origin and/or a natural antimicrobial agent of animal origin and, most preferably, at least one natural antimicrobial agent of vegetable origin from the group comprising caffeine, theobromine and theophylline and essential oils, such as eugenol, thymol and geraniol, and/or at least one natural antimicrobial agent of animal origin from the group comprising enzymes, such as protein from milk, lysozyme and lactoperoxidase and/or at least one antimicrobial surface-active quaternary compound containing an ammonium, sulfonium, phosphonium, iodonium or arsonium group, peroxo compounds and chlorine compounds. Substances of microbial origin, so-called bacterio- zines, may also be used.
The quaternary ammonium compounds (QUATS) suitable as antimicrobial agents have the general formula (R")R*)(R®*(R*N*X, in which R' to R* may be the same or different and represent Ci; alkyl groups, Cr.2 aralkyl groups or heterocyclic groups, two or - in the case of an aromatic compound, such as pyridine - even three groups together with the nitrogen atom forming the heterocycle, for example a pyridinium or imidazolinium compound, and X represents halide ions, sulfate ions, hydroxide ions or similar anions. In the interests of optimal antimicrobial
® ® WO 02/10356 63 PCT/EPO01/08359 activity, at least one of the substituents preferably has a chain length of 8 to 18 and, more preferably, 12 to 16 carbon atoms.
QUATS can be obtained by reaction of tertiary amines with alkylating agents such as, for example, methyl chloride, benzyl chloride, dimethyl sulfate, dodecyl bromide and also ethylene oxide. The alkylation of tertiary amines with one long alkyl chain and two methyl groups is particularly simple. The quaternization of tertiary amines containing two long chains and one methyl group can also be carried out under mild conditions using methyl chloride. Amines containing three long alkyl chains or hydroxy-substituted alkyl chains lack reactivity and are preferably quaternized with dimethyl sulfate.
Suitable QUATS are, for example, benzalkonium chloride (N-alkyl-
N,N-dimethylbenzyl ammonium chloride, CAS No. 8001-54-5), benzalkon B (m,p-dichiorobenzyl dimethyl-C4,-alkyl ammonium chloride, CAS No. 58390-78-6), benzoxonium chloride (benzyldodecyl-bis-(2-hydroxyethyl)- ammonium chloride), cetrimonium bromide (N-hexadecyl-N,N-trimethyl ammonium bromide, CAS No. 57-09-0), benzetonium chloride (N,N-di- methyl-N-[2-[2-[p-(1,1,3,3-tetramethylbutyl)}-phenoxy]-ethoxy]-ethyl]-benzyl ammonium chloride, CAS No. 121-54-0), dialkyl dimethyl ammonium chlorides, such as di-n-decyldimethyl ammonium chloride (CAS No. 7173- 51-5-5), didecyldimethyl ammonium bromide (CAS No. 2390-68-3), dioctyl dimethyl ammonium chloride, 1-cetylpyridinium chloride (CAS No. 123-03- 5) and thiazoline iodide (CAS No. 15764-48-1) and mixtures thereof.
Particularly preferred QUATS are the benzalkonium chlorides containing
Css alkyl groups, more particularly C12.14 alkyl benzyl dimethyl ammonium chloride.
Benzalkonium halides and/or substituted benzalkonium halides are commercially obtainable, for example, as Barquat® from Lonza, Marquat® from Mason, Variquat® from Witco/Sherex and Hyamine® from Lonza and as Bardac® from Lonza. Other commercially obtainable antimicrobial
® ® WO 02/10356 64 PCT/EP01/08359 agents are N-(3-chloroallyl)-hexaminium chioride, such as Dowicide® and
Dowicil® from Dow, benzethonium chloride, such as Hyamine® 1622 from
Rohm & Haas, methyl benzethonium chloride, such as Hyamine® 10X from
Rohm & Haas, cetyl pyridinium chloride, such as cepacolchloride from
Merrell Labs.
The antimicrobial agents are used in quantities of 0.0001% by weight to 1% by weight, preferably in quantities of 0.001% by weight to 0.8% by weight, more preferably in quantities of 0.005 to 0.3% by weight and most preferably in quantities of 0.01 to 0.2% by weight.
In addition, the compositions may optionally contain UV absorbers which are absorbed onto the treated textiles and improve the light stability of the fibers and/or the light stability of the other formulation ingredients.
UV absorbers are organic substances (light filters) which are capable of absorbing ultraviolet rays and of releasing the energy absorbed in the form of longer-wave radiation, for example heat.
Compounds which possess these desired properties are, for example, the compounds which act by radiationless deactivation and derivatives of benzophenone with substituents in the 2- and/or 4-position.
Other suitable UV absorbers are substituted benzotriazoles, 3-phenyl- substituted acrylates (cinnamic acid derivatives, optionally with cyano groups in the 2-position), salicylates, organic Ni complexes and natural substances, such as umbelliferone and the body’s own urocanic acid.
Particular significance attaches to the biphenyl and, above all, stilbene derivatives described, for example, in EP 0728749 A which are commercially available as Tinosorb® FD and Tinosorb® FR ex Ciba.
Suitable UV-B absorbers include 3-benzylidene camphor or 3-benzylidene norcamphor and derivatives thereof, for example 3-(4-methylbenzylidene)- camphor as described in EP-B1 0693471; 4-aminobenzoic acid derivatives, preferably 4-(dimethylamino)-benzoic acid-2-ethylhexyl ester, 4- (dimethylamino)-benzoic acid-2-octyl ester and 4-(dimethylamino)-benzoic
® ® WO 02/10356 65 PCT/EP01/08359 acid amyl ester; esters of cinnamic acid, preferably 4-methoxycinnamic acid-2-ethylhexyl ester, 4-methoxycinnamic acid propyl ester, 4- methoxycinnamic acid isoamyl ester, 2-cyano-3,3-phenylcinnamic acid-2- ethylhexyl ester (Octocrylene); esters of salicylic acid, preferably salicylic acid-2-ethylhexyl ester, salicylic acid-4-isopropylbenzyl ester, salicylic acid homomenthyl ester; derivatives of benzophenone, preferably 2-hydroxy-4- methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone; esters of benzalmalonic acid, preferably 4-methoxybenzmalonic acid di-2-ethylhexyl ester; triazine derivatives such as, for example, 2.4,6-trianilino-(p-carbo-2'-ethyl-1'- hexyloxy)-1,3,5-triazine and Octyl Triazone as described in EP 0818450 A1 or Dioctyl Butamido Triazone (Uvasorb® HEB); propane-1,3-diones such as, for example, 1-(4-tert.butylphenyl)-3-(4'-methoxyphenyl)-propane-1,3- dione; ketotricyclo(5.2.1.0)decane derivatives as described in EP 0694521
B1. Other suitable UV-B absorbers are 2-phenylbenzimidazole-5-sulfonic acid and alkali metal, alkaline earth metal, ammonium, alkylammonium, alkanolammonium and glucammonium salts thereof; sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzo- phenone-5-sulfonic acid and salts thereof; sulfonic acid derivatives of 3- benzylidene camphor such as, for example, 4-(2-oxo0-3-bornylidenemethyl)- benzene sulfonic acid and 2-methyl-5-(2-oxo-3-bornylidene)-sulfonic acid and salts thereof.
Typical UV-A filters are, in particular, derivatives of benzoyl methane such as, for example, 1-(4'-tert.butylphenyl)-3-(4'-methoxyphenyl)-propane- 1,3-dione, 4-tert.butyl-4'-methoxydibenzoyl methane (Parsol 1789), 1- phenyl-3-(4'-isopropylphenyl)-propane-1,3-dione and the enamine com- pounds described in DE 19712033 A1 (BASF). The UV-A and UV-B filters may of course also be used in the form of mixtures. Besides the soluble substances mentioned, insoluble light-blocking pigments, i.e. finely dispersed, preferably “nanoized” metal oxides or salts, may also be used
® ® WO 02/10356 66 PCT/EP01/08359 for this purpose. Examples of suitable metal oxides are, in particular, zinc oxide and titanium dioxide and also oxides of iron, zirconium oxide, silicon, manganese, aluminium and cerium and mixtures thereof. Silicates (talcum), barium sulfate and zinc stearate may be used as salts. The oxides and salts are used in the form of the pigments for skin-care and skin-protecting emulsions and decorative cosmetics. The particles should have a mean diameter of less than 100 nm, preferably between 5 and 50 nm and more preferably between 15 and 30 nm. They may be spherical in shape although ellipsoidal particles or other non-spherical particles may also be used. The pigments may also be surface-treated, i.e. hydrophilicized or hydrophobicized. Typical examples are coated titanium dioxides, for example Titandioxid T 805 (Degussa) and Eusolex® T2000 (Merck). Suitable hydrophobic coating materials are, above all, silicones and, among these, especially trialkoxyoctylsilanes or simethicones. Micronized zinc oxide is preferably used. Other suitable UV filters can be found in P. Finkel's review in SOFW-Journal 122, 543 (1996).
The UV absorbers are normally used in quantities of 0.01% by weight to 5% by weight and preferably 0.03% by weight to 1% by weight.
Proteins according to the invention and/or other proteins may also require special protection in detergents and cleaners. Compositions according to the invention may contain stabilizers for this purpose.
One group of stabilizers are reversible protease inhibitors which dissociate off on dilution of the composition in the wash liquor.
Benzamidine hydrochloride and leupeptin are established for this purpose.
Borax, boric acids, boron acids or salts or esters thereof, including above all phenylboron acids orthosubstituted by aromatic groups, for example in accordance with WO 95/12655, metasubstituted by aromatic groups in accordance with WO 92/19707 and parasubstituted by aromatic groups in accordance with US 5,972,873 or salts or esters thereof, are often used for this purpose. WO 98/13460 and EP 583 534 disclose peptide aldehydes,
_ | WO 02/10356 67 PCT/EP0O1/08359 i.e. oligopeptides with a reduced C-terminus, especially those of 2 — 50 monomers, for the reversible inhibition of detergent proteases. The peptidic reversible protease inhibitors include inter alia ovomucoid (WO 93/00418). WO 00/01826, for example, discloses specific reversible peptide inhibitors for the protease subtilisin for use in protease-containing compositions while WO 00/01831 discloses corresponding fusion proteins of protease and inhibitor.
Other enzyme stabilizers are aminoalcohols, such as mono-, di-, triethanol- and —propanolamine and mixtures thereof, aliphatic carboxylic acids up to C42 as known, for example, from EP 0 378 261 and WO 97/05227, such as succinic acid, other dicarboxylic acids or salts of the acids mentioned. End-capped fatty acid amide alkoxylates are disclosed for this purpose in German patent application DE 19650537. Certain organic acids used as builders are additionally capable of stabilizing an enzyme present, as disclosed in WO 97/18287.
Lower aliphatic alcohols, but above all polyols such as, for example, glycerol, ethylene glycol, propylene glycol or sorbitol are other frequently used enzyme stabilizers. According to a more recent application (EP 0 965 268), diglycerophosphate also stabilizes against denaturing by physical influences. Calcium salts, for example calcium acetate or the calcium formate disclosed for this purpose in EP 0 028 865, and magnesium salts, for example according to European patent application EP 0 378 262, are also used.
Polyamide oligomers (WO 99/43780) or polymeric compounds, such as lignin (WO 97/00932), water-soluble vinyl copolymers (EP 828 762) or, as disclosed in EP 702 712, cellulose ethers, acrylic polymers and/or polyamides stabilize the enzyme preparation inter alia against physical influences or pH variations. Polymers containing polyamine-N-oxide (EP 587 550 and EP 581 751) simultaneously act as enzyme stabilizers and as dye transfer inhibitors. Other polymer stabilizers are the linear Cg.1s
® ® WO 02/10356 68 PCT/EP01/08359 polyoxyalkylene disclosed besides other constituents in WO 97/05227.
Alkyl polyglycosides could stabilize the enzymatic components of the composition according to the invention and even enhance their performance, as disclosed in WO 97/43377 and WO 98/45396.
Crosslinked N-containing compounds, as disclosed in WO 98/17764, perform a dual role as soil release agents and as enzyme stabilizers.
Hydrophobic nonionic polymer in admixture with other stabilizers according to WO 97/32958 has a stabilizing effect on a cellulase so that these or similar constituents could also be suitable for the enzyme essential to the invention.
Reducing agents and antioxidants, as disclosed inter alia in EP 780 466, increase the stability of the enzymes to oxidative disintegration.
Sulfur-containing reducing agents are known, for example, from EP 0 080 748 and EP 0 080 223. Other examples are sodium sulfite (EP 533 239) and reducing sugars (EP 656 058).
In many cases, combinations of stabilizers are also used, for example the combination of polyols, boric acid and/or borax in WO 96/31589, the combination of boric acid or borate, reducing salts and succinic acid or other dicarboxylic acids in EP 126 505 or the combination of boric acid or borate with polyols or polyamino compounds and with reducing salts as disclosed in EP 080 223. According to WO 98/13462, the effect of peptide/aldehyde stabilizers is enhanced by combination with boric acid and/or boric acid derivatives and polyols and, according to WO 98/13459 is further enhanced by the additional use of calcium ions.
Compositions with stabilized enzyme activities represents preferred embodiments of the present invention. Compositions containing enzymes stabilized in several of the ways mentioned are particularly preferred.
Compositions according to the invention contain proteins or derivatives essential to the invention in quantities of preferably 0.000001% by weight to 5% by weight and, with increasing preference, in quantities of
® ® WO 02/10356 69 PCT/EP01/08359 0.00005 to 4% by weight, 0.00001 to 3% by weight, 0.0001 to 2% by weight and, in a most particularly preferred embodiment, in quantities of 0.001 to 1% by weight. The protein concentration can be determined by known methods, for example the BCA method (bicinchonic acid; 2,2’-biquinolyl- 4,4'-dicarboxylic acid) or the biuret method (A.G. Gornall, C.S. Bardawill and M.M. David, J. Biol. Chem. 177, (1948), pp. 751-766).
Besides the protein essential to the invention, compositions according to the invention may contain other amylolytic enzymes, more particularly a-amylases. These may also include the enzymes established for use in detergents/cleaners which were mentioned at the beginning.
Examples of commercially available amylases are BAN®, Termamyi®,
Purastar®, Amylase-LT®, Maxamyl®, Duramyl® and/or Purafect® Ox-Am.
This is advisable when the various enzymes are capable of complementing one another. Such complementing may occur, for example, in a regulatory sense, for example through mutual activation or inactivation. It may arise, for example, through at least a part of the enzyme essential to the invention, which is not homologous to the known a-amylases, having an influence on the amylolytic activities not essential to the invention.
However, the joint use can also be appropriate in view of differing substrate specificities. Both are embodiments of the present invention.
It can be of advantage, particularly with chemically diverse soils, to use amylolytic enzymes in detergents/cleaners together with other detersive enzymes and/or enzymes with cleaning activity. Accordingly, detergents/cleaners characterized by other enzymes besides a protein according to the invention represent preferred embodiments of the present invention.
Besides other amylases, for example proteases, these other enzymes include, for example, lipases, cutinases, esterases, pullulanases, cellulases, hemicellulases and/or xylanases and mixtures thereof.
Proteases, lipases, B-glucanases and/or cellulases are particularly
® ® WO 02/10356 70 PCT/EPO1/08359 preferred. Other enzymes add to the cleaning performance of corresponding compositions through their particular specific enzymatic activity. These include, for example, oxidoreductases or peroxidases as components of enzymatic bleaching systems, laccases (WO 00/39306), 3- glucanases (WO 99/06515 and WO 99/06516) or pectin-dissolving enzymes (WO 00/42145) which are used in particular in specialty detergents.
Examples of commercially obtainable enzymes for use in compositions according to the invention are proteases, such as subtilisin
BPN’, Properase®, BLAP®, Optimase®, Opticlean®, Maxatase®,
Maxacal®, Maxapem®, Alcalase®, Esperase®, Savinase®, Durazym®,
Everlase® and/or Purafect®G or Purafect®OxP, and lipases, such as
Lipolase®, Lipomax®, Lumafast® and/or Lipozym®.
The protease activity in such compositions may be determined by the method described in Tenside, Vol. 7 (1970), pp. 125-132. it is expressed accordingly, in PU (protease units). The protease activity of preferred compositions can be as high as 1,500,000 protase units per gram preparation (PU, as determined by the method described in Tenside, Vol. 7 (1970), pp. 125-132).
So far as their isolation is concerned, suitable enzymes are, above all, those obtained from microorganisms, such as bacteria or fungi, for example from Bacillus subtilis, Bacillus licheniformis, Streptomyces griseus,
Humicola lanuginosa, Humicola insolens, Pseudomonas pseudoalcaligenes or Pseudomonas cepacia, more particularly the enzyme mixtures formed naturally by these strains or mixtures with other strains.
They are isolated in known manner by fermentation processes from suitable microorganisms which are described, for example, in German
Offenlegungsschrifts DE 1940488 and DE 2121397, in US patents US 3,623,957 and US 4,264,738, in European patent application EP 006 638 and in International patent application WO 91/02792.
® ® WO 02/10356 71 PCT/EP01/08359
These optional additional enzymes may also be adsorbed onto carriers and/or encapsulated in membrane materials to protect them against premature inactivation, as described for example in Eurpean patent
EP 0 564 476 or in International patent application WO 94/23005. They are present in detergents in quantities of preferably up to 10% by weight and more particularly from 0.2% by weight to 2% by weight, enzymes stabilized against oxidative degradation - as known, for example, from International patent application WO 94/18314 - being particularly preferred.
Compositions according to the invention may consist of several phases, for example in order to release the active ingredients present separately from one another in time or space. The phases may be in various aggregate states but, in a particular embodiment, are two phases in the same aggregate state.
Compositions according to the invention which are made up of several solid components may readily be produced by mixing various powders or granules having various ingredients and/or different release behavior with one another in an overall loose form. The production of solid, single-phase or multi-phase compositions according to the invention can be carried out in known manner, for example by spray drying or granulation, the enzymes and optionally other heat-sensitive ingredients, such as bleaching agents for example, optionally being separately added at a later stage. Compositions according to the invention with a high bulk density, more particularly in the range from 650 to 950 g/l, are preferably produced by a process involving an extrusion step kown from EP 0 486 592. Another preferred production process based on granulation is described in
European patent EP 0 642 576.
Proteins can be used, for example, in dried, granulated, or encapsulated form or in encapsulated and additionally dried form for solid detergents/cleaners. They may be added separately, i.e. as a separate phase, or together with other constituents in the same phase without or
® ® WO 02/10356 72 PCT/EP01/08359 } without compacting. If microencapsulated enzymes are to be processed in solid form, the water can be removed from the aqueous solutions resulting from working up, for example by spray drying, centrifuging or resolubilization. The particles obtained in this way normally have a particle size of 50 to 200 pm.
The encapsulated form is appropriate for protecting the enzymes from other constituents, such as bleaching agents for example, or for facilitating controlled release. Depending on their size, the capsules are millicapsules, microcapsules or nanocapsules, microcapsules being particularly preferred for enzymes. Microcapsules are disclosed, for example, in patent applications WO 97/24177 and DE 19918267. In another possible encapsulation process which starts out from a mixture of the enzyme solution with a solution or suspension of starch or a starch derivative, the enzymes suitable for use in detergents or cleaners are encapsulated in starch or the starch derivative. One such encapsulation process is described in German application DE 19956382 “A process for the production of microencapsulated enzymes”.
Another method of producing a solid composition according to the invention is tabletting or compacting. The tablets produced may be single- phase or multi-phase tablets. Accordingly, this supply form also enables a solid composition according to the invention to be produced with two solid phases. To produce compositions according to the invention in the form of single-phase or multi-phase, single-color or multi-color tablets which may consist of several layers, all the constituents — optionally per layer — may be mixed together in a mixer and the resulting mixture may be tabletted in conventional tablet presses, for example eccentric presses or rotary presses, under applied pressures of about 50 to 100 kN.cm? and preferably 60 to 70 kN/cm? With multilayer tablets in particular, it can be of advantage for at least one layer to be pre-compressed. This is preferably done by applying pressures of 5 to 20 kN/cm? and more particularly 10 to
® ® WO 02/10356 73 PCT/EPO1/08359 15 kN/cm?. A tablet produced in this way preferably has a weight of 10 g to 50 g and more particularly 15 g to 40 g. The tablets The tablets may be of any shape, including round, oval or angular and variations thereof.
The enzymes and even a protein essential to the invention - starting from a conventionally performed protein isolation and preparation in concentrated aqueous or nonaqueous solution - may be added to liquid, gel-form or paste-form compositions according to the invention, for example, in liquid form, i.e. as a solution, suspension or emulsion, but also in gel form or in encapsulated form or as a dried powder. Such detergents or cleaners according to the invention in the form of solutions in typical solvents are generally prepared by simple mixing of the ingredients which may be introduced into an automatic mixer as such or in the form of a solution.
An embodiment of the invention are liquid, gel-form or paste-form compositions to which a protein essential to the invention and/or one of the other proteins present and/or one of the other ingredients present have been added in the form of microcapsules. Corresponding compositions containing capsules of amylase-sensitive material are particularly preferred.
The use of amylase-sensitive materials and the amylolytic enzyme essential to the invention together in a detergent or cleaner can have synergistic effects, for example such that the starch-splitting enzyme supports the splitting of microcapsules and hence the release of the encapsulated ingredients so that they are only released at a certain time and not during storage and/or not at the beginning of the cleaning process.
This mechanism can form the basis of complex detergent or cleaning systems containing various ingredients and various types of capsules which represent preferred embodiments of the present invention.
A comparable effect is observed when the ingredients of the detergent or cleaner are distributed among at least two different phases, for example two or more solid, joined-together phases of a tablet-form
® ® WO 02/10356 74 PCT/EP01/08359 detergent or cleaner or various granules within the same powder-form detergent/cleaner. Two-phase or multi-phase cleaners for use both in dishwashers and in detergents are already known. The activity of an amylolytic enzyme in a previously activated phase is essential for the activation of a later phase where it is surrounded by an amylase-sensitive membrane or coating or the amylase-sensitive material is an integral part of the solid phase during whose partial or complete hydrolysis the phase in question disintegrates. Accordingly, the use of the enzyme essential to the invention for this purpose is a preferred embodiment of the present invention.
The ingredients of detergents/cleaners are able suitably to support one another in their performance. The synergistic use of amylase and dye transfer inhibitors for increasing cleaning performance is disclosed, for example, in patent application WO 99/63035. it is also known that polymers which can simultaneously be used as co-builders, such as alkyl polyglycosides for example, can stabilize and increase the activity and the stability of enzymes present, cf. patent application WO 98/45396. An amylolytic activity essential to the invention can also be modified, more particularly stabilized and/or increased, by one of the other constituents mentioned above. Accordingly, correspondingly adapted formulations for compositions according to the invention represent particularly preferred embodiments of the present invention. This applies in particular when the washing or cleaning performance of the composition is increased in this way.
The basic concept of the present invention is also embodied in processes for cleaning textiles or hard surfaces which are characterized in that an amylolytic protein or derivative according to the invention becomes active in at least one of the process steps.
Machine cleaning processes are distinguished by multistage cleaning programs, i.e. by the fact that various components with cleaning
® ® WO 02/10356 75 PCT/EP01/08359 activity are applied to the articles to be cleaned at different times from one another. Such processes are applied, for example, in the cleaning of institutional food preparation units. On the other hand, proteins essential to the invention, by virtue of their enzymatic activity, are themselves capable o> of attacking carbohydrate-containing soils, even in the partial or complete absence of detergents or other ingredients characteristic of detergents or cleaners. Accordingly, in one embodiment of the present invention, a machine cleaning process for textiles or hard surfaces may also be selected in which a protein essential to the invention acts on the soils for a certain period without other cleaning-active components.
Preferred embodiments of the present invention are any cleaning processes, including manual, but especially machine cleaning processes, which are characterized in that an amylolytic protein or derivative essential to the invention becomes active in at least one of the process steps. Such processes may be both process for cleaning textiles or comparable materials and processes for cleaning hard surfaces.
As shown in the Examples, the a-amylase from Bacillus sp. A 7-7 (DSM 12368) essential to the invention is suitable, when incorporated in appropriate detergents or cleaners, both for increasing the washing performance of machine detergents for textiles and for increasing the cleaning performance of dishwasher detergents.
Accordingly, other preferred embodiments of the present invention are any cleaning processes, including manual, but especially machine cleaning processes, which are characterized in that a composition according to the invention is used in at least one of the process steps.
Such processes may be both processes for cleaning textiles or comparable materials and processes for cleaning hard surfaces.
Quantities of protein or fragment according to the invention particularly suitable for use in cleaning processes, for example in conventional domestic dishwashers or domestic washing machines, are
® ® WO 02/10356 76 PCT/EP01/08359 0.02 mg to 400 mg of the amylolytic protein or fragment, preferably 0.01 mg to 200 mg and more particularly 0.02 mg to 100 mg of the amylolytic enzyme or fragment per application.
In one possible embodiment of machine cleaning processes for textiles or hard surfaces, active concentrations of 0.0005 mg to 10 mg per liter wash liquid and preferably 0.005 mg to 8 mg per liter wash liquor have proved to be particularly suitable for a protein essential to the invention.
Accordingly, they represent preferred embodiments of the present invention. In other suitable embodiments, the corresponding values may differ significantly from the above figures, particularly when it is taken into account that machines consuming between 5 and 50 liters of wash liquor for virtually the same quantity of detergent are used for machine cleaning processes.
The use of a protein according to the invention or a composition according to the invention represents another embodiment of the present invention. This use may take place by machine or in any other, more particularly manual, way. This concerns the cleaning of all kinds of materials, more particularly textiles or hard surfaces. The protein essential to the invention may be embedded in a formulation of other detersive substances or, depending on its nature, may even be largely unaccompanied by such compounds.
Another corresponding embodiment is the use of a protein according to the invention on its own for cleaning textiles or hard surfaces, more particularly in a multistage cleaning process.
A preferred embodiment are any potential applications where compositions according to the invention for cleaning textiles or hard surfaces are used.
An important use is characterized in that the amylolytic protein or fragment is used in a quantity of 0.02 mg to 400 mg, preferably 0.01 mg to 200 mg and more particularly 0.02 mg to 100 mg per application in a
® ® WO 02/10356 77 PCT/EPO1/08359 dishwasher or washing machine.
The use of proteins or derivatives according to the invention for completely or partly dissolving protective layers around constituents of solid detergents or cleaners or disintegrating solid phases with amylase- sensitive materials present in, or surrounding, them is another embodiment : of the present invention. The same also applies to the embodiments where amylolytic proteins are present in one of these phases either on their own or together with at least one other detersive substance or an active substance which supports the cleaning effect. To this extent, the amylolytic protein is intended to activate the relevant phases or other phases in a detergent or cleaner consisting of more than one phase. The release of the ingredients to produce a cleaning effect of the ingredients on hard surfaces or a textile-like material is particularly preferred from this perspective also.
The use of the enzyme according to the invention to achieve the partial or complete dissolution of carbohydrate-containing capsules, more especially nanocapsules, microcapsules or millicapsules, in liquid, gel-form or paste-form compositions is an embodiment of the present invention of which the significance for the controlled release of the encapsulated ingredients of the compositions has already been discussed in the foregoing. This embodiment is a particularly preferred embodiment of the invention when the ingredients are released to produce a cleaning effect on a hard surface or a textile-like material.
Another embodiment is the use of a protein or derivative according to the invention for the treatment of raw materials or intermediate products in textile manufacture, more particularly for desizing cotton.
Raw materials and intermediate products for textile production, for example those based on cotton, are finished with starch during their production and further processing in order to facilitate better processing.
This process, which is applied both to yarns and intermediate products and to textiles, is known as sizing. Amylolytic proteins according to the
® ® WO 02/10356 78 PCT/EPO1/08359 ] invention are suitable for removing the size, i.e. the starch-containing protective layer (desizing).
Another embodiment of the invention are processes for liquefying starch, more particularly for producing ethanol, which are characterized in that they use a protein or derivative according to the invention.
For liquefying starch, starch swollen in water or buffer is incubated with amylolytic enzymes so that the polysaccharide is split into smaller constituents, ultimately mainly into maltose. Enzymes according to the invention are preferably used for such a process or for one of the steps it involves where their biochemical properties allow them to be readily integrated into a corresponding production process. This may the case, for example, when they are to be introduced into a process step in addition to other enzymes which require the same reaction conditions. Amylolytic proteins according to the invention are particularly preferred where the products which they themselves form are the focus of interest. The liquefaction of starch may also represent one step in a multistage process for producing ethanol or derivatives thereof, for example acetic acid.
Another embodiment of the invention is the use of a protein or derivative according to the invention for the production of linear and/or short-chain oligosaccharides.
By virtue of their enzymatic activity, amylolytic proteins according to the invention mainly form relatively high molecular weight oligosaccharides, such as maltohexaose, maltoheptaose or maltooctaose for example, from starch-like polymers after a relatively short incubation period. After a relatively long incubation period, there is an increase in the proportion of lower oligosaccharides, such as maltose or maltotriose for example, among the reaction products. Where there is a particular interest in certain reaction products, corresponding variants of proteins according to the invention and/or the reaction conditions may be modified accordingly. This is particularly attractive when pure compounds are not the main concern,
® ® WO 02/10356 79 PCT/EP01/08359 but rather mixtures of similar compounds as, for example, in the formation of solutions, suspensions or gels having only certain physical properties.
Another embodiment is the use of a protein or derivative according to the invention for the hydrolysis of cyclodextrins.
Cyclodextrins are «-1,4-glycosidic cyclic oligosaccharides among which those of 6, 7 or 8 glucose monomers, the a-, B- and y-cyclodextrins (or cyclohexa-, -hepta- or —octa-amyloses), have the greatest economic importance. With hydrophobic guest molecules, such as perfumes, flavors or pharmaceutical active principles for example, they are capable of forming inclusion compounds from which the guest molecules can be released as required. Depending on the field of application of the ingredients, such inclusion compounds are of importance, for example, for the production of foods, pharmaceutical or cosmetic products, for example in corresponding products for the end consumer. Accordingly, the release of ingredients from cyclodextrins is a practical application for proteins according to the invention.
Another embodiment is the use of a protein or derivative according to the invention for the release of low molecular weight compounds from polysaccharide carriers or cyclodextrins.
By virtue of their enzymatic activity, amylolytic proteins according to the invention are also capable of releasing low molecular weight compounds from other a-1,4-glycosidic polysaccharides. As with the cyclodextrins, this can take place at the molecular level and even on larger systems such as, for example, ingredients encapsulated in the form of microcapsules. Starch, for example, is an established material for encapsulating such compounds as, for example, enzymes - which are to be introduced into reaction mixtures in defined quantities — during storage.
The controlled release process from such capsules can be supported by amylolytic enzymes according to the invention.
Another embodiment is the use of a protein or derivative according
® ® WO 02/10356 80 PCT/EP01/08359 to the invention for the production of foods and/or food ingredients.
The use of a protein or derivative for the production of animal feed and/or animal feed ingredients is another embodiment of the present invention.
Wherever starch or starch-derived carbohydrates play a role as ingredients of foods or animal feeds, an amylolytic activity may be used for the production of these articles. It increases the proportion of mono- or oligomers in relation to the polymeric sugar which can be to the benefit of the taste, digestibility or consistency of the food. This may be necessary for the production of certain animal feeds and also, for example, in the production of fruit juices, wine or other foods if the level of polymeric sugars is to be reduced and the level of sweet and/or more readily soluble sugars increased. The above-mentioned application for liquefying starch and/or producing ethanol may be regarded as an industrial variant of this principle.
In addition, amylases also counteract the loss of taste from bread and confectionery through staleness (anti-staling effect). To this end, they are suitably added to the dough before baking. Accordingly, preferred embodiments of the present invention are those in which proteins according to the invention are used for the production of bread and confectionery.
Another embodiment is the use of a protein or derivative according to the invention for dissolving starch-containing adhesive bonds.
Temporary bonding processes which are characterized in that they use a protein or derivative according to the invention represent another embodiment of the present invention
Besides other natural materials, starch has been used for centuries as a binder in paper manufacture and in the bonding of different papers and paperboards. This applies, for example, to graphics and books. Over long periods, such papers can become wavy or can break under "30 unfavorable influences, such as moisture for example, resulting in their
® ® WO 02/10356 81 PCT/EP01/08359 complete destruction. To restore such papers and boards, it may be necessary to dissolve the adhesive layers which is made very much easier by the use of an amylolytic protein according to the invention. Vegetable polymers, such as starch or cellulose and water-soluble derivatives thereof, are used as adhesives or pastes. To this end, they first have to be swollen in water and then dried after application to the surface to be glued so that it is fixed to the substrate. The enzyme according to the invention may be added to such an aqueous suspension in order to influence the adhesive properties of the paste formed. However, instead of or in addition to this function, it may also be added to the paste in order to stay inactive on the surface for a long time after drying, for example for a few years. Controlled changes in the ambient conditions, for example through moistening, can be used to activate the enzyme at a later date and hence to induce dissolving of the paste. In this way, the glued surface is easier to separate from the substrate. In this process, the enzyme according to the invention, through its amylolytic activity, acts as a separating agent in a temporary bonding process or as a so-called “switch” for separating the glued article. . Examples
Example 1 :
The candidates for a microbiological screening for amylase-forming microorganisms with the selection criterion growth and halo formation on agar plates with starch as sole carbon source included the Bacillus strain
Bacillus sp. (RNA group VI, alcaliphilic) A 7-7 which has been lodged at the
DSMZ (DSM ID 98-587, lodgement DSM 12368).
The culture medium used was YPSS medium containing 15 g/l soluble starch, 4 g/l yeast extract, 1 g/l K;HPO4 and 0.5 g/l MgSOq4 x 7 H20.
After autoclaving, the pH was adjusted to 10.3 with 20% sodium carbonate solution. Quantities of 25 ml medium were introduced into sterile 100 mi
® ® WO 02/10356 82 PCT/EPQO1/08359
Erlenmeyer flasks with chicane and inoculated with a culture of Bacillus sp.
A 7-7 (DSM 12368) which had been grown on a YPSS agar plate.
Cultivation was carried out with shaking over 48 h at 30°C/200 r.p.m.
Example 2
A singular enzyme was obtained from the culture medium through the following purification steps: precipitation of the culture supernatant with ethanol; taking up the protein pellet in 50 mM tris/HCI buffer, pH 8.5; dialysis against 50 mM tris/HCl buffer, pH 8.5; cation exchange chromatography on Fast-flow-S-Sepharose® (Pharmacia-Amersham
Biotech, Freiburg) with 50 mM tris/HCI buffer, pH 8.5 as eluent; rebuffering of the amylase-containing break-through against 20 mM glycine/NaOH buffer, pH 10, in PD10® columns (Pharmacia-Amersham Biotech); anion exchange chromatography on Mono-Q® (Pharmacia-Amersham Biotech) using the same buffer as eluent with an increasing salt gradient of 0 to 1 M
NaCl. The amylase eluted at ca. 0.25 M NaCl. 2.6 mg of a protein were obtained in this way from 250 ml of culture medium, as determined by the BCA method (bicinchonic acid; 2,2'- biquinolyl-4,4’-dicarboxylic acid). The protein was shown to be pure by
SDS gel electrophoresis and coloring with silver.
In denaturing SDS polyacrylic gel electrophoresis in an 8-25% gel in the PHAST® system (Pharmacia-Amersham) and in comparisons with relevant size markers, the amylolytic enzyme from Bacillus sp. A 7-7 (DSM 12368) has a molecular weight of 58 kD.
According to isoelectric focussing from pH 3 to 9 in the PHAST® system (Pharmacia-Amersham), its isoelectric point lies at 6.0.
The amylolytic activity of the purified enzyme was determined by the so-called DNS method, i.e. using dinitrosalicylic acid. To this end, the oligosaccharides, disaccharides and glucose units released by the enzyme in the hydrolysis of starch are detected by oxidation of the reducing ends
® ® WO 02/10356 83 PCT/EP01/08359 with dinitrosalicylic acid (DNS). The intensity of color development is proportional to the number of cleavage products formed. This test is carried out as follows: after incubation of 50 pl enzyme solution with 100 pl 1% soluble starch in tris/maleate buffer, pH 6.5 (12.11 g tris + 11.61 g maleic acid to 1 liter, pH adjusted with 0.2 N NaOH) for 15 mins. at 50°C, the reduced saccharides are oxidized for 20 mins. at 100°C with 300 pl
DNS solution (8.8 g dinitrosalicylic acid, 915 ml distilled water, 250 g K-Na tartrate, 334 ml 4.5% NaOH, 6.3 g sodium disulfite). After cooling in an ice bath, absorption is photometrically detected at 540 nm against a blank value. The assay is calibrated via a maltose concentration series. The activity is expressed in pmol reducing sugars (based on maltose) per min. and ml.
According to this test, the protein of the Examples clearly has amylolytic activity. In the following, the activity determined in this way serves as a parameter for the stability of the enzyme under various conditions.
The temperature stability of the enzyme was measured in 10-minute incubations at a pH of 10. At room temperature, 30°C, 40°C and 50°C, the activity is at least 85%. At 40°C, the amylase has its maximum of 90% residual activity. At 60°C, the enzyme has 50% activity. At temperatures above 60°C, it undergoes a serious loss of activity, but still has 10% residual activity at 80-90°C.
The amylolytic enzyme from Bacillus sp. A 7-7 (DSM 12368) is largely stable at pH values of 5 to 12 when incubated for 10 mins. at 40°C.
At pH values of 8 to 9, the amylase is up to 100% stable. At higher and lower pH values, its activity slowly decreases although the enzyme still has more than 65% residual activity at pH 5 and pH 12.
For further characterization, the adverse effect on enzymatic activity of possibly disturbing factors, such as protease or detergents, is investigated. After exposure to 10 HPE/ml of the protease Savinase®
® ® WO 02/10356 84 PCT/EP01/08359 (Novo Nordisk A/S, Bagsvaerd, Denmark; the HPE units can be determined by the method reported in Tenside 7 (1970), pp. 125-132) and 0.1% SDS for 15 minutes at pH 10/50°C, the enzyme shows 74% residual activity.
After exposure to 0.1% SDS under the same conditions (pH 10, 15 minutes, 50°C), the enzyme has 98% residual activity. Still under these conditions, it has 10% residual activity in the presence of 3 mM EDTA and 65% residual activity in the presence of 1 mM EDTA.
Example 3
All molecular-biological process steps follow standard methods which are described, for example, in manuals such as the manual by
Fritsch, Sambrook and Maniatis entitled “Molecular cloning: a laboratory manual”, Cold Spring Harbour Laboratory Press, New York, 1989.
In order to determine internal amino acid sequences, the protein obtained in accordance with Example 1 and purified in accordance with
Example 2 was first precipitated with ethanol and then separated by denaturing SDS polyacrylic gel electrophoresis. After the corresponding bands had been cut out from the SDS polyacrylamide gel, digestion was carried out tryptically in situ, the resulting peptides were separated by
HPLC and analyzed by Edman degradation and MELDI-TOF analysis. The following two fragments (D1 and D6) were selected from the many tryptic fragments obtained in this way:
D1: GITAVWIPPAWK 5-GTN TGG ATH CCN CCN CGN TGG- 3
D6: QGYPSVFYGDYYGIPTH 5-CGD ATN CCN TAN TAR TCN CC-3'
The corresponding degenerated PCR primers were constructed from their amino acid sequences (shown on the left). Their nucleotide sequences are shown on the right (N stands for any bases; H stands for A
® @® WO 02/10356 85 PCT/EPO1/08359 or C or T; R stands for A or G; D stands for A, G or T).
From normally prepared chromosomal DNA of Bacillus sp. A 7-7 (DSM 12368) as matrix, a ca. 1,000 bp large fragment was amplified with this primer pair in a standard PCR. For storage, this PCR fragment was cloned in the vector pGEM-Teasy® (Promega, Madison, Wisconsin, USA).
Example 4
Using the nonradioactive DIG-High-Prime® labeling kit of
Boehringer Mannheim (Germany: product No. 1245832), the purified PCR fragment was labeled as directed as a DNA probe. For subsequent hybridization, chromosomal DNA of the strain Bacillus sp. A 7-7 (DSM 12368) was split with the restriction enzyme Xba 1 and separated via a 0.9% agarose gel. The DNA was transferred by a vacuum blotter to a positively charged nylon membrane (Roche, Mannheim). DNA hybridizdation and immunological detection of the PCR fragment used as probe were carried out according to the directions of the DIG-High-Prime®
Labeling-and-Detection Starter Kits I® of Boehringer Mannheim. It was found that the target gene is present in an apparently ca. 3,000-4,000 large
DNA section. The fragments of this size were purified via a 0.9% agarose gel and then ligated in the vector pCB56C (from B. Subtilis DB 104; described in application WO 91/02792) cut with the restriction enzymes
Xba | and Nhe |. After transformation in an amylase-negative Bacillus subtilis strain, amylase-positive clones were identified through halo formation on starch-containing agar plates. A representative isolate carried the required insert.
Example 5
The sequencing of the plasmid obtained was carried out by standard chain termination methods. The plasmid contained an insert with a size of 2,015 bp. On top lies the 1,545 bp large gene for the interesting enzyme
® ® WO 02/10356 86 PCT/EPQ1/08359 which is shown under SEQ ID NO. 1 in the sequence protocol of the present application. To this corresponds a polypeptide of 516 amino acids of which the sequence is shown in SEQ ID NO. 2 in the sequence protocol.
The molecular weight derived from this amino acid sequence is 59 kD or — for the mature protein obtained by splitting off the signal peptide with 31 amino acids — 55.5 kD.
Sequence comparisons by the BLAST method (S.F. Altschul et al.,
Nucl. Acids Res., 25 (1997), pp. 3389-3402) carried out on 17.03.2000 characterize the enzyme as a-amylase. At the protein level, the homology of this protein to known proteins is between 71 and 95% identity, as shown in Table 2 below.
Table 2
Homology of the enzyme according to the invention from Bacillus sp. A 7-7 (DSM 12368) to the most similar and other representative proteins; expressed in % identity at protein level. ID stands for the entries at the
Swiss Prot Data Bank (Geneva, Switzerland). “Organism ID Identity[%] "B. alcalophilus ~~ P19571 95
B. alcalophilus WO 96/23873 91
B. licheniformis P 06278 72
B. amyloliquefaciens P 00692 72
B. stearothermophilus P 06297 71
An alignment with representative proteins is shown in Fig. 1. All the proteins are a-amylases so that, on the basis of the substantial accords, it must be assumed that the enzyme according to the invention is also an a- amylase. This is in line with the original isolation of the gene from a starch- degrading microorganism (Example 1) and the discovery of the amylolytic activity of a transformant with the insert-carrying plasmid (Example 4). The
® ® WO 02/10356 87 PCT/EP01/08359 properties of the amylolytic protein obtainable from this production strain correspond with those of the wild type strain (Example 2). Such a production strain can be produced in accordance with Example 4.
Example 6
Cotton fabrics were treated under standardized conditions with the four different soils A (chocolate mousse), B (oat flakes with cocoa), C (oat flakes with cocoa and a little milk) and D (potato starch) and, using the material thus prepared, various detergent formulations were launderometer-tested for washing performance. For the tests, a liquor ratio of 1:12 was adjusted and the fabrics were washed for 30 mins. at 30°C.
The dosage was 5.88 g of the particular detergent per liter wash liquor.
The water hardness was 16° German hardness.
The control detergent for A, B and C was a basic detergent with the following composition (in % by weight): 4% linear alkyl benzenesulfonate (sodium salt), 4% C12.4s fatty alcohol sulfate (sodium salt), 5.5% C12.1s fatty alcohol x 7 EO, 1% sodium soap, 11% sodium carbonate, 2,5% amorphous sodium disilicate, 20% sodium perborate tetrahydrate, 5.5% TAED, 25% zeolite A, 4.5% polycarboxylate, 0.5% phosphonate, 2.5% granular foam inhibitor, 5% sodium sulfate, 1% protease granules, rest: water, optical brightener, perfume, salts. For the various test series, various amylases were added to the control detergent so that the final concentration was 44
TAU of amylolytic activity per liter wash liquor.
The amylolytic activity in TAU was determined using a modified p- nitrophenyl maltoheptaoside of which the terminal glucose unit is blocked by a benzylidene group which is split by amylase to free p-nitrophenyl : oligosaccharide which in turn is reacted with the auxiliary enzymes glucoamylase and alpha-glucosidase to form glucose and p-nitrophenol.
The quantity of p-nitrophenol released is thus proportional to the amylase activity. The measurement is carried out, for example, with an Abott Quick-
® ® WO 02/10356 88 PCT/EP01/08359
Start® Testkit (Abott Park, Illinois, USA). The increase in absorption (405 nm) in the test mixture is detected over 3 mins. at 37°C against a blank value using a photometer. An enzyme standard of known activity is used for calibration (for example Maxamyl®/Purastar® of Genencor with an activity of 2,900 TAU/g). Evaluation is carried out by plotting the absorption difference dE (40 5nm) per min. against the enzyme concentration of the standard.
The amylolytic enzyme according to the invention from Bacillus sp. A 7-7 (DSM 12368) was compared with Termamyl®, Duramyl® and BAN® (manufacturer: Novo Nordisk A/S, Bagsvaerd, Denmark). The detergent used for soil D was the same basic formulation, but without protease, used as control for A-C or with added amylases.
In the present Example, the whiteness of the fabrics in the CIELAB system was measured before and after washing with a Minolta CR 310 in comparison with a standard which was standardized to 100%. The differences in the results obtained are set out in Table 3 below for the respective tests. The average values of 5 measurements are shown. They are a direct indication of the contribution of the enzyme present to the washing performance of the detergent used.
Table 3. a TR LS LR LA LA oo
Amylase essential to the invention | essential to the invention EE
Sendarddeviaton [18 [06 [14 [22
® ® WO 02/10356 89 PCT/EPO1/08359 it can be seen that the a-amylase from Bacillus sp. A 7-7 (DSM 12368) produces distinctly better washing performances against soil B than any of the three reference enzymes. Against the other soils, it shows slightly improved washing performance (within the limit of error) although this is still well above the comparison values without amylolytic enzyme.
This result is all the more conclusive insofar as all the detergent formulations tested contain a bleaching agent to which wild type enzymes are generally very sensitive.
Example 7
Cotton fabrics were treated under standardized conditions with soils :
B (oat flakes with cocoa) and C (oat flakes with cocoa and a little miik).
Launderometer testing was carried out as in Example 1 using another detergent formulation, namely (in % by weight): 14% Na alkyl benzenesulfonate, 6% Na fatty alcohol sulfate, 6% 7x-ethoxylated Cis.1s fatty alcohol, 1% soap, 25% zeolite NaA, 10% Na carbonate, 5% polymeric polycarboxylate (Sokalan® CP5), 11% trisodium citrate dihydrate, 4% citric acid, 1% particulate foam inhibitor, 1% protease granules, 5% sodium sulfate, rest: water and salts. For the various test series, various amylases were added to this basic formation so that the final concentration was 33.5
TAU of amylolytic activity per liter of wash liquor, as determined by the method described in Example 1. The amylolytic enzyme essential to the invention from Bacillus sp. A 7-7 (DSM 12368) was compared with
Termamyl®, Duramyl® and BAN® (manufacturer: Novo Nordisk A/S,
Bagsvaerd, Denmark). The dosage was 4.45 g of the particular detergent per liter wash liquor.
After washing, the whiteness of the washed fabrics was determined in the same way as in the preceding Example. The differences obtained are set out in Table 4 and represent the average values of 5 measurements which, again, are a direct indication of the contribution of the particular
® ® WO 02/10356 90 PCT/EPO1/08359 enzyme to the washing performance of the detergent.
Table 4.
Basic detergentcontaining | B | ©
Seddon | a8 | 12
It can be seen that the a-amylase from Bacillus sp. A 7-7 (DSM 12368) in this bleach-free detergent formulation produces better washing performance against soils B and C than any of the reference enzymes.
Example 8
Cotton fabrics were soiled under standardized conditions with two different types of commercially available milk cocoa (E and F).
Launderometer testing was then carried out as described in Example 1.
The control detergent used was the basic detergent formulation of Example 2, but without protease. For the various test series, the various amylases were added in the same way as in Example 2. The detergent was used in the same dosage.
After washing, the whiteness of the washed fabrics was measured in comparison with that of barium sulfate which was standardized to 100%.
The measurement was carried out using a Datacolor SF500-2 spectrometer at 460 nm (UV blocking filter), 30 mm orifice, without gloss, light type D65, 10°, d/8°. The results obtained are set out as % reflectance, i.e. as percentages in comparison with barium sulfate, in Table 4 below
® ® WO 02/10356 91 PCT/EP01/08359 which also shows the particular starting value. The values shown are the averages of 5 measurements and are a direct indication of the contribution of the amylolytic enzyme present to the washing performance of the detergent used.
Table 5.
Basic detergent containing | BE | F
It can be seen that the a-amylase from Bacillus sp. A 7-7 (DSM 12368) in this formulation produces distinctly better washing performance in the case of E than any of the reference systems tested and, in the case of F, comparable washing performance.
Example 9
For application-oriented cleaning tests, vessels with hard smooth surfaces were provided with the following soils under standardized conditions: A (DIN oat flakes), B (oat flakes swollen in water) and C (mixed starch), and were washed at 45°C with the normal program of a domestic dishwasher (Miele® G 575). The detergent dosage was 20 g per cleaning cycle and the water hardness was 16° German hardness.
The following basic formulation was used as the detergent (all quantities in % by weight): 55% sodium tripolyphosphate (expressed as
® ® WO 02/10356 92 PCT/EP01/08359 water-free), 4% amorphous sodium disilicate (expressed as water-free), 22% sodium carbonate, 9% sodium perborate, 2% TAED, 2% nonionic surfactant, 1.4% protease granules, rest: water, dyes, perfume. For the various tests, various amylases, namely Termamyl®, Duramyl®, BAN® (manufacturer: Novo Nordisk A/S, Bagsvaerd, Denmark), or the amylolytic enzyme from Bacillus sp. A 7-7 (DSM 12368) were added to the basic formulation in effective quantities of 150 TAU of amylolytic activity per cleaning cycle, as determined by the method described in Example 1.
After washing, the removal of soil A was evaluated after coloring with iodine by the iodine/starch reaction, evaluation being carried out visually on a scale of 0 (= unchanged, i.e. very pronounced soil) to 10 (=no soil discernible). The removal of soils B and C was determined gravimetrically in %. To this end, the difference between the weight of the soiled and then cleaned vessel and the starting weight of the vessel was related to the difference in weight between the uncleaned vessel and its starting weight. This relation may be regarded as percentage removal.
The results obtained are set out in Table 6 below where they are shown as the averages of 9 measurements for A and B and 18 measurements for C. They are a direct indication of the contribution of the enzyme present to the cleaning performance of the detergent used.
Table 6. (Boskc eorgortcortaig | A] ® | © _ [a [wena a cS LI NLA
® ® WO 02/10356 93 PCT/EP01/08359
These results show that the a-amylase from Bacillus sp. A 7-7 (DSM 12368) is superior to all the other amylases tested in its cleaning performance against all three soils in dishwasher detergents at 45°C.
Example 10
Vessels with hard smooth surfaces were provided with the same soils as in the preceding Example and washed at 55°C. The cleaning conditions and the formulation of the detergents used also corresponded to those of the preceding Example.
After washing, the removal of soil A was visually evaluated as in
Example 4 on a scale of 0 to 10 using the iodine/starch reaction. The removal of soils B and C was determined gravimetrically in %, again as in
Example 4. The results obtained are set out in Table 6 below where they are shown as the averages of 9 measurements for A, 10 measurements for
B and 18 measurements for C. They are a direct indication of the contribution of the enzyme present to the cleaning performance of the detergent used.
Table 6. bis SN NE LAN NL [Sw [wea
Rill) IC A
LC IC HE
3 I
These results show that the a-amylase from Bacillus sp. A 7-7 (DSM 12368) is superior to all the other amylases tested in its cleaning
® @® WO 02/10356 94 PCT/EP01/08359 performance against all three soils in dishwasher detergents, even at a dishwashing temperature of 55°C.
Figure 1:
Alignment of the amylolytic enzyme according to the invention from Bacillus sp. A 7-7 (DSM 12368) with the three most similar amylases.
In Fig. 1, 1 = amylase from Bacillus sp. A7-7 (DSM 12368) 2 = mature amylase from Bacillus sp. # 707 according to: Tsukamoto,
Kimura, Ishii, Takano and Yamane, Biochem. Biophys. Res.
Common. 151 (1988), pp.25-31 3 = amylase of SEQ ID NO. 1 from WO 96/23873 4 = amylase of SEQ ID NO. 2 from WO 96/23873
Claims (1)
- ® ® WO 02/10356 95 PCT/EP01/08359 CLAIMS1. Amylolytic protein with an amino acid sequence which is at least 96% identical with the amino acid sequence shown in SEQ ID NO. 2.2. Amylolytic protein with an amino acid sequence which is at least 98% identical with the amino acid sequence shown in SEQ ID NO. 2.3. Amylolytic protein with an amino acid sequence which is at least 96% identical with the amino acid sequence shown in SEQ ID NO. 2 in positions 32 to 516.4. Amylolytic protein with an amino acid sequence which is at least 98% identical with the amino acid sequence shown in SEQ ID NO. 2 in positions 32 to 516.5. Amylolytic protein derived from a nucleotide sequence which is at least 85% identical with the nucleotide sequence shown in SEQ [ID NO. 1, more particularly over the partial region which corresponds to amino acids 321to 516 in SEQ ID NO. 2.6. Amylolytic protein derived from a nucleotide sequence which is at least 90% identical with the nucleotide sequence shown in SEQ ID NO. 1, more particularly over the partial region which corresponds to amino acids 32 to 516 in SEQ ID NO. 2.17. Amylolytic protein which is identical with the amino acid sequence shown in SEQ ID NO. 2 as a whole and/or in positions 32 to 516 and/or which is identical with an amino acid sequence derived from the nucleotide sequence shown in SEQ ID NO. 1 as a whole and/or in positions 32 to 516.8. Amylolytic protein fragment or amylolytic protein as claimed in any of claims 1 to 7 obtainable by deletion mutation.9. Amylolytic protein obtainable by insertion mutation or amylolytic chimeral protein consisting at least partly of an amylolytically active part of a protein identical with the protein or fragment claimed in any of claims 1 to8.10. Amylolytically active derivative of the protein claimed in any of® ® WO 02/10356 96 PCT/EPO1/08359 claims 1 to 9.11. Amylolytic protein or derivative which has at least one antigenic determinant in common with one of the proteins or derivatives claimed in claims 1 to 10.12. Amylolytic protein or derivative as claimed in any of claims 1 to 11, characterized in that it is naturally obtainable from a microorganism.13. Amylolytic protein or derivative as claimed in claim 12, characterized in that the microorganism is a gram-positive bacterium.14. Amylolytic protein or derivative as claimed in claim 13, characterized in that the gram-positive bacterium is one of the genus Bacillus.15. Amylolytic protein or derivative as claimed in claim 14, characterized in that the Bacillus species is Bacillus sp. A 7-7 and more particularly Bacillus sp. A 7-7 (DSM 12368).16. Nucleic acid coding for an amylolytic protein of which the nucleotide sequence is at least 85% identical with the nucleotide sequence shown in SEQ ID NO. 1, more particularly over the partial region which corresponds to amino acids 32 to 516 in SEQ ID NO. 2.17. Nucleic acid coding for an amylolytic protein of which the nucleotide sequence is at least 90% identical with the nucleotide sequence shown in SEQ ID NO. 1, more particularly over the partial region which corresponds to amino acids 32 to 516 in SEQ ID NO. 2.18. Nucleic acid coding for an amylolytic protein which is 100% identical with the nucleotide sequence shown in SEQ [ID NO. 1, more particularly over the partial region which corresponds to amino acids 32 to 516 in SEQ ID NO. 2.19. Nucleic acid which codes for one of the proteins or derivatives claimed in claims 1 to 15.20. Natural organism forming one of the proteins or derivatives claimed in claims 1 to 15 or containing nucleic acids coding for those proteins or derivatives.® @® WO 02/10356 97 PCT/EP01/0835921. Organism as claimed in claim 20, characterized in that it is a microorganism, preferably a bacterium.22. Organism as claimed in claim 21, characterized in that the bacterium is a gram-positive bacterium.23. Organism as claimed in claim 22, characterized in that the gram- positive bacterium is one of the genus Bacillus, more particularly Bacillus sp. A 7-7 and most particularly Bacillus sp. A 7-7 (DSM 12368).24. Vector containing a nucleic acid region according to claims 16 to 19 or a nucleic acid region which codes for one of the proteins or derivatives claimed in claims 1 to 15.25. Cloning vector according to claim 24. : 26. Expression vector according to claim 24.27. Cell containing the vector claimed in any of claims 24 to 26.28. Host cell which expresses one of the proteins or derivatives claimed in claims 1 to 15 or which can be stimulated to express that protein or derivative, preferably using the expression vector claimed in claim 26.29. Host cell as claimed in claim 28, characterized in that it is a bacterium, more particularly one which secretes the protein or derivative formed into the surrounding medium.30. Host cell as claimed in claim 28 or 29, characterized in that it is a bacterium of the genus Bacillus, more particularly of the species Bacillus licheniformis, Bacillus amyloliquefaciens, Bacillus subtilis or Bacillus alcalophilus.31. Host cell as claimed in claim 28 or 29, characterized in that it is a gram-negative bacterium.32. Host cell as claimed in claim 31, characterized in that it belongs to the genus Escherichia, preferably to the species Escherichia coli and more preferably to one of the strains E. coli JM 109, E. coli DH 100B or E. coli DH 12S.33. Host cell as claimed in claim 28, characterized in that it is a® @ WO 02/10356 98 PCT/EP0O1/08359 eukaryotic cell, more particularly one which posttranslationally modifies the protein formed.34. Process for the production of the protein or derivative claimed in any of claims 1 to 15 using the nucleic acid claimed in any of claims 16 to 19 and/or using the vector claimed in any of claims 24 to 26 and/or using the host cell claimed in any of claims 28 to 33 or using a cell which naturally forms the protein or derivative, more particularly the cell claimed in any of claims 20 to 23.35. Detergent or cleaner, characterized in that it contains the protein or derivative claimed in any of claims 1 to 15.36. Detergent or cleaner as claimed in claim 35, characterized in that it contains 0.000001% by weight to 5% by weight and more particularly0.00001 to 3% by weight of the amylolytic protein or derivative.37. Detergent or cleaner as claimed in claim 35 or 36, characterized in that it additionally contains one or more other amylolytic proteins, more particularly a-amylases.38. Detergent or cleaner as claimed in any of claims 35 to 37, characterized in that it additionally contains other enzymes, more particularly one or more proteases, lipases, p-glucanases and/or cellulases.39. Detergent or cleaner as claimed in any of claims 35 to 38, characterized in that it consists of more than one phase.40. Detergent or cleaner as claimed in any of claims 35 to 39, characterized in that it is solid and in that at least two different powders or granules are present in admixture with one another in an overall lose form.41. Detergent or cleaner as claimed in claim 39, characterized in that at least two solid phases are joined to one another, more particularly after a common compacting step.42. Detergent or cleaner as claimed in any of claims 39 to 41, characterized in that at least one of the phases contains an amylase- sensitive material, more particularly starch, or is at least partly surrounded® ® WO 02/10356 99 PCT/EPO1/08359 by or coated with that material.43. Detergent or cleaner as claimed in any of claims 35 to 42, characterized in that it is liquid, gel-like or paste-like and the protein present and/or at least one of the enzymes present and/or at least one of the other components present is/are encapsulated on its own or together with other constituents, preferably in microcapsules and more particularly in microcapsules of an amylase-sensitive material.44. Detergent or cleaner as claimed in any of claims 35 to 43, characterized in that the amylolytic activity is modified by one of the other constituents of the detergent/cleaner, more particularly stabilized and/or increased in the contribution it makes to the washing/cleaning performance of the detergent/cleaner.45. Process for cleaning textiles or hard surfaces, characterized in that the amylolytic protein or derivative claimed in any of claims 1 to 15 becomes active in at least one of the process steps.46. Process for cleaning textiles or hard surfaces, characterized in that the detergent/cleaner claimed in any of claims 35 to 44 is used in at least one of the process steps.47. Process as claimed in claim 45 or 46, characterized in that the amylolytic protein or derivative is used in the process step in question in a quantity of 0.01 mg to 200 mg per application and preferably in a quantity of 0.02 mg to 100 mg per application.48. Use of the amylolytic protein or derivative claimed in any of claims 1 to 15 on its own or together with at least one other detersive agent or an active substance supporting the cleaning effect for cleaning textiles or hard surfaces.49. Use of the detergent claimed in any of claims 35 to 44 for cleaning textiles or hard surfaces.50. Use claimed in claim 48 or 49, characterized in that the amylolytic protein or derivative is used in a quantity of 0.01 mg to 200 mg and® ® WO 02/10356 100 PCT/EP01/08359 preferably in a quantity of 0.02 mg to 100 mg per application, preferably per application in a dishwasher or washing machine.51. Use of the amylolytic protein or derivative claimed in any of claims 1 to 15 on its own or together with at least one other detersive agent or an active substance supporting the cleaning effect in a detergent or cleaner consisting of more than one phase for activating those or other phases.52. Use of the amylolytic protein or derivative claimed in any of claims 1 to 15 on its own or together with at least one other detersive agent or an active substance supporting the cleaning effect in a detergent or cleaner containing encapsulated ingredients for releasing the ingredients from the capsules.53. Use of the protein or derivative claimed in any of claims 1 to 15 for the treatment of raw materials or intermediate products in textile manufacture, more particularly for desizing cotton.54. A process for liquefying starch, more particularly for producing ethanol, characterized in that the protein or derivative claimed in any of claims 1 to 15 is used therein.55. Use of the protein or derivative claimed in any of claims 1 to 15 for the production of linear and/or short-chain oligosaccharides.56. Use of the protein or derivative claimed in any of claims 1 to 15 for the hydrolysis of cyclodextrins.57. Use of the protein or derivative claimed in any of claims 1 to 15 for releasing low molecular weight compounds from polysaccharide carriers or cyclodextrins. :58. Use of the protein or derivative claimed in any of claims 1 to 15 for the production of foods and/or food ingredients.59. Use of the protein or derivative claimed in any of claims 1 to 15 for the production of animal feed and/or animal feed ingredients.60. Use of the protein or derivative claimed in any of claims 1 to 15 for dissolving starch-containing adhesive bonds.® ® WO 02/10356 101 PCT/EPO1/0835961. Temporary bonding process, characterized in that the protein or derivative claimed in any of claims 1 to 15 is used therein.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE2000136752 DE10036752C2 (en) | 2000-07-28 | 2000-07-28 | Detergent and cleaning agent with a new amylolytic enzyme from Bacillus sp. A 7-7 (DSM 12368) |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200300721B true ZA200300721B (en) | 2003-11-10 |
Family
ID=7650493
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200300721A ZA200300721B (en) | 2000-07-28 | 2003-01-27 | Novel amylolytic enzyme extracted from Bacillus sp. A 7-7 (DSM 12368) and washing and cleaning agents containing this novel amylolytic enzyme. |
Country Status (2)
Country | Link |
---|---|
DE (1) | DE10036752C2 (en) |
ZA (1) | ZA200300721B (en) |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE69534464T2 (en) * | 1994-03-29 | 2006-09-28 | Novozymes A/S | ALKALIC AMYLASE FROM BACELLUS |
EP2302027B1 (en) * | 1997-10-13 | 2013-08-28 | Novozymes A/S | Alpha-amylase mutants |
EP2386569B1 (en) * | 1997-10-30 | 2014-08-06 | Novozymes A/S | Alpha-amylase mutants |
-
2000
- 2000-07-28 DE DE2000136752 patent/DE10036752C2/en not_active Expired - Fee Related
-
2003
- 2003-01-27 ZA ZA200300721A patent/ZA200300721B/en unknown
Also Published As
Publication number | Publication date |
---|---|
DE10036752A1 (en) | 2002-02-21 |
DE10036752C2 (en) | 2003-02-20 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US7303905B2 (en) | Amylolytic enzyme extracted from Bacillus sp. A 7-7 (DSM 12368) and washing and cleaning agents containing this novel amylolytic enzyme | |
US7888104B2 (en) | Cyclodextrin glucanotransferase (CGTase), obtained from<I>Bacillus agaradherens<λ>(DSM 9948) and detergents and cleaning agents containing said novel cyclodextrin glucanotransferase | |
US7300782B2 (en) | Glycosyl hydrolases | |
US20050049165A1 (en) | Detergent and cleaning agent with hybrid alpha-amylases | |
US8080401B2 (en) | Alpha-amylase variants having an elevated solvent stability, method for the production thereof and detergents and cleansers containing these alpha-amylase variants | |
US8785365B2 (en) | Alpha-amylase variants stabilized against dimerization and/or multimerization, method for the production thereof, and detergents and cleansers containing these alpha-amylase variants | |
US20090275493A1 (en) | Novel Alkaline Protease from Bacillus Gibsonii and Washing and Cleaning Agents containing said Novel Alkaline Protease | |
US20050026269A1 (en) | Novel alkaline protease variants and detergents and cleaning agents containing said novel alkaline protease variants | |
US20050043198A1 (en) | Alkaline protease from Bacillus sp. (DSM 14392) and washing and cleaning products comprising said alkaline protease | |
US20050003504A1 (en) | Alkaline protease from Bacillus gibsonii (DSM 14391) and washing and cleaning products comprising said alkaline protease | |
JP2007533312A (en) | Novel alkaline protease and detergent and detergent containing the novel alkaline protease | |
US20090258406A1 (en) | Use of esterases for separating plastics | |
ZA200300721B (en) | Novel amylolytic enzyme extracted from Bacillus sp. A 7-7 (DSM 12368) and washing and cleaning agents containing this novel amylolytic enzyme. |