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(12) Patent Application Publication (10) Pub. No.: US 2016/0319266A1 Kolkman Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2016/0319266A1 Kolkman Et Al US 201603 19266A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0319266A1 Kolkman et al. (43) Pub. Date: Nov. 3, 2016 (54) SERINE PROTEASES OF THE BACILLUS Related U.S. Application Data GIBSONI-CLADE (60) Provisional application No. 61/915,737, filed on Dec. (71) Applicant: DANISCO US INC., Palo Alto, CA 13, 2013, provisional application No. 62/069,200, (US) filed on Oct. 27, 2014. (72) Inventors: Marc Kolkman, Oegstgeest (NL); Rie Publication Classification Mejldal, Ostbirk (DK); Frits Goedegebuur, Vlaardingen (NL); Lilia (51) Int. Cl. Maria Babe, Emerald Hills, CA (US); CI2N 9/54 (2006.01) Anja Hemmingsen Kellett-Smith, A47L I3/00 (2006.01) Arhuc (DK); Harm Mulder. Oegstgeest CLID 3/386 (2006.01) (NL); Richard R. Bott, Burlingame, (52) U.S. Cl. CA (US); Miles Christopher Scotcher, CPC ............... CI2N 9/54 (2013.01): CI2Y 304/21 Hayward, CA (US) (2013.01): CIID 3/386 (2013.01); A47L (73) Assignee: Danisco US Inc., Palo Alto, CA (US) 15/0002 (2013.01); A47L 2601/20 (2013.01) (21) Appl. No.: 15/104,219 (57) ABSTRACT (22) PCT Filed: Dec. 12, 2014 The present disclosure relates to serine proteases cloned from Bacillus gibsonii, and variants thereof. Compositions (86). PCT No.: PCT/US1.4/70 107 containing the serine proteases are Suitable for use in clean 371 C)(1),1 1nging fabriTabr1cS andd hardnard SurTaces,Surf as wellll as i1n a Var1elyiety ofo (2) Date: Jun. 13, 2016 industrial applications. Patent Application Publication Nov. 3, 2016 Sheet 1 of 18 US 2016/0319266 A1 eft - iambda apfs promoter region signai peptide apt Tet R. PRO Bgio2446 RBs precursor April. SP-8gio24.46 -10 Signal y nature chain Bgi02A46 -35 Signal x - s Y. Repori (pAMalpha-1} pHY-BgiO2446a - STOP codon RaS 2. $870 bp f terminator 0 Signal 2 -35 Signal 2 -10 Signal 3 Gramt origin 2 -35 Signal 3 -35 Signal 4. Amp R (Et3 from paCYC177} -to Signal 4. RBS 3 FIG. 1 : 1. pp. protease FIG.2 Patent Application Publication Nov. 3, 2016 Sheet 2 of 18 US 2016/0319266 A1 O.S . OC (eit & Krachtig * Kirkiac tra 1. 8 3 s - s 1. protease ppi. FIG.3A . * CO coir 2 ** a tra S 0.1 8 5 0. s s protease ppm FIG.3B Patent Application Publication Nov. 3, 2016 Sheet 3 of 18 US 2016/0319266 A1 8 -o- pH 9 r- p 10.5 s $ 0.4 8 W . S 1. Protease ppm FIG. 3C Patent Application Publication Nov. 3, 2016 Sheet 8 of 18 US 2016/0319266 A1 0.05 Patent Application Publication Nov. 3, 2016 Sheet 9 of 18 US 2016/0319266 A1 OMO HDL O,5 - B gibsonii DSM9728 0.4 A B gibsonii DSM973 E 0.3 3. 0.2 a 0. 0.0 O 1 2 3 4. 5 ppm Protease in assay FIG. 7A OMO HDD O,5 - B gibsonii DSM9728 0.4 -Air B gibsonii DSM973 E 0.3 S. 0.2 O. 0.0 O 2 3 4. 5 ppm Protease in assay FIG. 7B Patent Application Publication Nov. 3, 2016 Sheet 10 of 18 US 2016/0319266A1 Quantum pH9 Unrinsed O A - B gibsonii DSM9728 A A B gibsonii DSM973i 0.5 0.0 O 2 4. 6 ppm Protease in assay FIG. 7C Quantum pH9 Rinsed 0.8 - B gibsonii DSM9728 A B gibsonii DSM973 O 2 4. 6 ppm Protease in assay FIG. 7D Patent Application Publication Nov. 3, 2016 Sheet 11 of 18 US 2016/0319266A1 GSM-B pH10 Unrinsed 1.4 A. 2 -- B gibsonii DSM9728 O A B gibsonii DSM9731 E 0.8 0.6 0.4 0.2 0,,O O 2 4. 6 ppm Protease in assay FIG. 7E GSM-B pH10 Rinsed O -- B-gibsonii DSM9728 a A B gibsonii DSM9731 E g 0.5 w C 0.0 O 2 4. 6 ppm Protease in assay FIG. 7F Patent Application Publication Nov. 3, 2016 Sheet 13 of 18 US 2016/0319266 A1 Patent Application Publication Nov. 3, 2016 Sheet 14 of 18 US 2016/0319266A1 AD. triad FIG. 9 Patent Application Publication Nov. 3, 2016 Sheet 18 of 18 US 2016/0319266A1 ------------ 833-808 (8.306; ri 8GS-E32 (.812) '-------- 886-A; ) (8.8033} 8(35-60 (3.0034) '.................... 836-88 (8.0338 ... 838-F82 (33.339: 83-85 (8.8038 ----------------------. 832-808 (0.332; ... 832-10 : 00:3} ii........... 832-338 0083: ;............................................................ 834A39 (3.8238 ... 834-33 (0.382 :- 888-883 0.3228 : BSka9728 (3 2009) - CAE4842.1 (3.3(28 ... CAS91385. (.3088; ''----------------------------'-'-'-'l'-'l'-'-'------ £833854 {3,3288 } .....OS88738 (8.8033} DS84973) {0.3085) ir 835-E06 (0.0372} 8g.02448 (8.8992 ....... ESA/3223 (0.035) F.G. US 2016/0319266 A1 Nov. 3, 2016 SERINE PROTEASES OF THE BACILLUS and the penultimate H is the active site Histidine, and X is GIBSONI-CLADE any amino acid. Another embodiment is directed to a recom binant polypeptide, or active fragment thereof, of the B. CROSS REFERENCE TO RELATED gibsonii-clade that has proteolytic activity and comprises an APPLICATIONS amino acid sequence of SEQ ID NO:47 or 90, wherein the 0001. This application claims the benefit of U.S. Provi initial D is the active site Aspartic acid residue and the sional Patent Application No. 61/915,737, filed Dec. 13, penultimate H is the active site Histidine, and X is any amino 2013, and 62/069,200, filed Oct. 27, 2014, wherein the acid, with the proviso that the B. gibsonii-clade does not contents of both provisional applications are hereby incor comprise WO03054184-CAE48421, WO2007 131657 CAS91385, WO2008086916-CAV33594, or NCBI Acces porated herein by reference in their entirety. Sion No. AGS784O7. FIELD 0008. Yet a further embodiment is directed to a recom binant polypeptide, or active fragment thereof, of the B. 0002 The present disclosure relates to serine proteases gibsonii-clade, wherein the recombinant polypeptide, or the cloned from Bacillus gibsonii, and variants thereof. Com active fragment thereof, having proteolytic activity and positions containing the serine proteases are Suitable for use comprising an amino acid sequence of SEQID NO:47 or 90 in cleaning fabrics and hard Surfaces, as well as in a variety further comprises an amino acid sequence having at least of industrial applications. 70% identity to the amino acid sequence of SEQ ID NO:4, 7, 11, 15, 19, 23, 49, 50, 51, 52, 57, 59, 61, 63, 65, 67, 69, BACKGROUND 71, 73, 75, 77, 79, 81, or 83. 0003 Serine proteases are enzymes (EC No. 3.4.21) 0009. Yet a further embodiment is directed to a recom possessing an active site serine that initiates hydrolysis of binant polypeptide, or active fragment thereof, of the B. peptide bonds of proteins. There are two broad categories of gibsonii-clade, wherein the recombinant polypeptide, or the serine proteases, based on their structure: chymotrypsin-like active fragment thereof, having proteolytic activity and (trypsin-like) and subtilisin-like. The prototypical subtilisin comprising an amino acid sequence of SEQID NO:47 or 90 (EC No. 3.4.21.62) was initially obtained from B. subtilis. further comprises an amino acid sequence having at least Subtilisins and their homologues are members of the S8 70% identity to the amino acid sequence of SEQID NO:11, peptidase family of the MEROPS classification scheme. 15, 19, 23, 49, 50, 51, 52, 57, 59, 61, 63, 65, 67, 69, 71, 73, Members of family S8 have a catalytic triad in the order Asp, 75, 77, 79, 81, or 83. His and Ser in their amino acid sequence. 0010 Yet a further embodiment is directed to a recom 0004 Although serine proteases have long been known in binant polypeptide, or active fragment thereof, of the B. the art of industrial enzymes, there remains a need for gibsonii-clade, wherein the recombinant polypeptide, or the further serine proteases that are suitable for particular con active fragment thereof, having proteolytic activity and ditions and uses. comprising an amino acid sequence of SEQID NO:47 or 90 further comprises an amino acid sequence having at least SUMMARY 70% identity to the amino acid sequence of SEQID NO: 57. 0005. The present compositions and methods relate to B 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, or 83. gibsonii-clade Subtilisins, including recombinant serine pro 0011 Still further embodiments are directed to a recom teases cloned from Bacillus gibsonii, and variants thereof. binant polypeptide, or active fragment thereof, of the B. The present compositions and methods further relate to gibsonii-clade, wherein the recombinant polypeptide, or the recombinant serine proteases of the B. gibsonii-clade gen active fragment thereof, having proteolytic activity and erated through conventional molecular biology techniques comprising an amino acid sequence of SEQID NO:47 or 90 (see, e.g., Sambrook et al. Molecular Cloning: Cold Spring further comprises an amino acid sequence having at least Harbor Laboratory Press). Compositions containing the ser 70% identity to the amino acid sequence of SEQ ID NO:4, ine proteases are Suitable for use in cleaning fabrics and hard 7, 11, 15, 19, 23, 49, 50, 51, 52, 57, 59, 61, 63, 65, 67, 69, Surfaces, as well as in a variety of industrial applications. 71, 73, 75, 77, 79, 81, or 83, with the proviso that the B. 0006. Some embodiments are directed to a recombinant gibsonii-clade does not comprise WOO3054184-CAE48421, polypeptide, or an active fragment thereof, of the B. gib WO2007 131657-CAS91385, WO2008086916-CAV33594, sonii-clade, wherein the recombinant polypeptide or active or NCBI Accession No. AGS78407. fragment thereof has proteolytic activity.
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