IP Library Granted Patent US 12,369,597
Granted Patent B2
US 12,369,597 · App. 16/604,134 · Granted Jul 29, 2025

Lactase enzymes with improved activity at low temperatures

Inventors: Hans Raj (Hoersholm, DK); Pernille Smith (Broenshoej, DK); Thomas Eckhardt (Birkeroed, DK); Vojislav Vojinovic (Graested, DK); Charlotte Elisabeth Grüner Schöller (Virum, DK); Johannes Maarten Van Den Brink (Herlev, DK)
Assignee: Kerry Group Services International Ltd
A23C9/1206C12N9/2471
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Quick Facts
Patent No.
US 12,369,597
App. No.
16/604,134
Granted
Jul 29, 2025
Kind
B2
Abstract

The present invention relates to new improved peptide or dimeric peptides exhibiting beta-galactosidase enzyme activity as well as improved methods for reducing the lactose content in compositions in particular at low temperatures.

Claims (29)

1. A method for producing a dairy product, comprising:

(a) mixing a milk-based substrate comprising lactose at a concentration of at least 10 g/L and a peptide or a dimeric peptide exhibiting beta-galactosidase activity at a concentration of 10 to 55 mg/L; and

(b) incubating the mixture at a temperature from 1° C.-10° C. for a period of time sufficient to reduce the lactose concentration in the mixture to less than 0.2 g/L,

wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is selected from a peptide having the amino acid sequence of any one of SEQ ID NOs. 1-6 or 8-33, or a variant thereof having from 1 to 22 amino acid substitutions, additions, or deletions, and exhibits beta-galactosidase enzyme activity at a temperature from 1° C.-10° C.

2. A method for reducing the lactose content in a milk-based substrate, comprising:

(a) mixing a milk-based substrate comprising lactose at a concentration of at least 10 g/L and a peptide or a dimeric peptide exhibiting beta-galactosidase activity at a concentration of 10 to 55 mg/L; and

(b) incubating the mixture at a temperature from 1° C.-10° C. for a period of time sufficient to reduce the lactose concentration in the mixture to less than 0.2 g/L,

wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is selected from a peptide having the amino acid sequence of any one of SEQ ID NOs. 1-6 or 8-33, or a variant thereof having from 1 to 22 amino acid substitutions, additions, or deletions, and exhibits beta-galactosidase enzyme activity at a temperature from 1° C.-10° C.

3. The method according to claim 1 , wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is selected from a peptide having the amino acid sequence of any one of SEQ ID NOs. 22, 33, 14, 9, 11, 30 or 1, or a variant thereof having from 1 to 22 amino acid substitutions, additions, or deletions.

4. The method according to claim 1 , wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is added at a concentration of 35 to 52 mg/L.

5. The method according to claim 1 , wherein the milk-based substrate comprising lactose is selected from:

(i) a pasteurized, raw, and/or filtered form of cow milk, sheep milk, goat milk, buffalo milk, or camel milk; or

(ii) a fermented dairy product obtained from (i) by fermentation.

6. The method according to claim 5 , wherein the milk-based substrate comprising lactose is cow milk comprising lactose at a concentration of about 37 to 50 g/L, or a heat treated, pasteurized, and/or filtered form thereof.

7. The method according to claim 1 , wherein the lactose concentration of less than 0.2 g/l is reached after incubation for 4-24 hours.

8. The method according to claim 1 , wherein the incubation temperature in step (b) is in the range of from 2° C.-7° C.

9. The method according to claim 1 , wherein the incubation in step (b) reduces the lactose concentration in the mixture to less than 0.05 g/L.

10. The method according to claim 1 , wherein the mixture comprising the milk-based substrate and the peptide or the dimeric peptide exhibiting beta-galactosidase activity is heated to a temperature of at least 60° C. for at least four seconds before or after incubating the mixture at a temperature from 1° C.-10° C.

11. The method according to claim 10 , wherein the mixture comprising the milk-based substrate and the peptide or the dimeric peptide exhibiting beta-galactosidase activity is heated to a temperature of 72° C. for about 15 seconds before or after incubating the mixture at a temperature from 1° C.-10° C. in step (b).

12. The method according to claim 1 , wherein the method comprises a step of fermenting the milk-based substrate with lactic acid bacteria.

13. The method according to claim 12 , wherein the fermentation step is carried out before or after the incubation with the peptide or the dimeric peptide exhibiting beta-galactosidase activity.

14. The method according to claim 1 , wherein the dairy product is selected from a fermented milk product, cheese, yoghurt, butter, dairy spread, butter milk, acidified milk drink, sour cream, whey based drink, ice cream, condensed milk, dulce de leche, and a flavored milk drink.

15. The method according to claim 1 , wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is selected from a peptide having the amino acid sequence of any one of SEQ ID NOs. 13, 19, 26, or 27, or a variant thereof having from 1 to 22 amino acid substitutions, additions, or deletions.

16. The method according to claim 1 , wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is added at a concentration of 45 to 52 mg/L.

17. The method according to claim 1 , wherein the lactose concentration of less than 0.2 g/l lactose is reached after incubation for 24 hours.

18. The method according to claim 1 , wherein the incubation in step (b) reduces the lactose concentration in the mixture to less than 0.01 g/L.

19. The method according to claim 10 , wherein the mixture comprising the milk-based substrate and the peptide or the dimeric peptide exhibiting beta-galactosidase activity is heated to a temperature of 140° C. for about four seconds before or after incubating the mixture at a temperature from 1° C.-10° C.

20. The method according to claim 1 , wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is selected from a peptide having the amino acid sequence of any one of SEQ ID NOs. 1-6 or 8-33, or a variant thereof having from 1 to 5 amino acid substitutions, additions, or deletions.

21. The method according to claim 2 , wherein the peptide or the dimeric peptide exhibiting beta-galactosidase activity is selected from a peptide having the amino acid sequence of any one of SEQ ID NOs. 1-6 or 8-33, or a variant thereof having from 1 to 5 amino acid substitutions, additions, or deletions.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 3, 2024
From: CHR. HANSEN A/S
To: KERRY GROUP SERVICES INTERNATIONAL LTD
Reel/Frame 067309/0489 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2020
From: RAJ, HANS; SMITH, PERNILLE; ECKHARDT, THOMAS; VOJINOVIC, VOJISLAV; SCHÖLLER, CHARLOTTE ELISABETH GRÜNER; VAN DEN BRINK, JOHANNES MAARTEN
To: CHR. HANSEN A/S
Reel/Frame 051470/0924 →
Priority Claims (2)
EP 17166021 · Apr 11, 2017 · regional
EP 17188732 · Aug 31, 2017 · regional
Continuity (1)
Related Publication 20230210121A1 · Jul 6, 2023
References Cited (144)
US 8030049B2 · Tzortzis et al. · 2011 [cited by applicant]
US 10058107B2 · Hendriksen et al. · 2018 [cited by applicant]
US 10306902B2 · Hendriksen et al. · 2019 [cited by applicant]
US 10555541B2 · Hendriksen et al. · 2020 [cited by applicant]
US 11525129B2 · Raj et al. · 2022 [cited by applicant]
US 20090110770A1 · Tzortzis · 2009 [cited by examiner]
US 20090117080A1 · Tzortzis et al. · 2009 [cited by applicant]
US 20090297660A1 · Silver et al. · 2009 [cited by applicant]
US 20100113383A1 · Mills et al. · 2010 [cited by applicant]
US 20100285175A1 · Hendriksen · 2010 [cited by examiner]
US 20120058223A1 · Stougaard et al. · 2012 [cited by applicant]
US 20160333331A1 · De Jong · 2016 [cited by examiner]
US 20170215449A1 · Nagahata et al. · 2017 [cited by applicant]
US 20190343138A1 · Ba et al. · 2019 [cited by applicant]
US 20200120946A1 · Hendriksen et al. · 2020 [cited by applicant]
US 20200123519A1 · Bongiorni et al. · 2020 [cited by applicant]
US 20210032615A1 · Raj et al. · 2021 [cited by applicant]
US 20210037844A1 · Hendriksen et al. · 2021 [cited by applicant]
US 20210348147A1 · Raj et al. · 2021 [cited by applicant]
US 20210355471A1 · Raj et al. · 2021 [cited by applicant]
US 20230076578A1 · Raj et al. · 2023 [cited by applicant]
CN 103431042B · 2015 [cited by applicant]
EP 1227152A1 · 2002 [cited by applicant]
EP 2530148A1 · 2012 [cited by applicant]
EP 2957180B1 · 2015 [cited by applicant]
RU 2278160C2 · 2005 [cited by applicant]
RU 2009120742 · 2010 [cited by applicant]
WO WO2005084411A2 · 2005 [cited by applicant]
WO WO2005086794A2 · 2005 [cited by applicant]
WO WO2007088324A1 · 2007 [cited by applicant]
WO WO2007110619A1 · 2007 [cited by applicant]
WO WO2008033520A2 · 2008 [cited by applicant]
WO WO2009009142A2 · 2009 [cited by applicant]
WO WO2009071539A1 · 2009 [cited by applicant]
WO WO2010092057A1 · 2010 [cited by applicant]
WO WO2013160413A1 · 2013 [cited by applicant]
WO WO2015107050A1 · 2015 [cited by applicant]
WO WO2017216000A1 · 2017 [cited by applicant]
WO WO2018041869A1 · 2018 [cited by applicant]
WO WO2018130630A1 · 2018 [cited by applicant]
WO WO2018187524A1 · 2018 [cited by applicant]
WO WO2018189224A1 · 2018 [cited by applicant]
WO WO2018189238A1 · 2018 [cited by applicant]
Seq Alignment Result (16604134 SEQ #7vs Tzortis SEQ #2 using SLIC and ABSS SEQ-to SEQ (aa), PI note : copied sequence from SLIC had MET instead of M which were aligned(MET 3 letters) instead of one ‘M’ even if ABSS SEQ-… [cited by examiner]
Cecchini et al. (This ref was considered from Result 2 of Uniport (426 kb) as posted on and collected from “Search Results” [as posted on Feb. 1, 2022 ] from U.S. Appl. No. 16/604,129-A (matches SEQ ID #22 99.4% match a… [cited by examiner]
Wierzbicka-Woś et al. Microbial Cell Factories 2011, 10:108 (Year: 2011). [cited by examiner]
Google search Result for Wierzbicka-Wos et al. [Retrieved on Apr. 14, 2024]. (Year: 2024). [cited by examiner]
Broune et al. “Catalytic Plasticity of Fatty Acid Modification Enzymes Underlying Chemical Diversity of Plant Lipids,” Science, vol. 282, pp. 1315-1317 (1998). [cited by applicant]
Devos et al., “Practical Limits of Function Prediction,” Proteins: Structure, Function, and Genetics, vol. 41, pp. 98-107 (Aug. 2000). [cited by applicant]
Seffernick et al., “Melamine Deaminase and Atrazine Chlorohydrolase: 98 Percent Identical but Functionally Different,” Journal of Bacteriology, vol. 183, No. 8, pp. 2405-2410 (Apr. 2001). [cited by applicant]
Whisstock et al., “Prediction of protein function from protein sequence and structure,” Quarterly Reviews of Biophysics, vol. 36, No. 3 (pp. 307-340) (2003). [cited by applicant]
Witkowski et al. “Conversion of β-Ketoacyl Synthase to a Malonyl Decarboxylase by Replacement of the Active-Site Cysteine with Glutamine,” Biochemistry, vol. 38, pp. 11643-11650 (1999). [cited by applicant]
“Chapter 3 Lactose content of milk and milk products,” The American Journal of Clinical Nutrition, vol. 48, No. 4 pp. 1099-1044 (Oct. 1988) Available online, URL: https://academic.oup.com/ajcn/article-abstract/48/4/1099… [cited by applicant]
Kreft et al., “Lactose hydrolysing ability of sonicated cultures of [cited by applicant]
Office Action issued on Jun. 9, 2021, in Application No. U.S. Appl. No. 16/998,706 (US 2021-0032615). [cited by applicant]
Rhimi et al., “Exploring the acidotolerance of B-galactosidase from [cited by applicant]
UNIPROT:G6F860 (Oct. 2020). [cited by applicant]
Van De Guchte, et al., Beta-galactosidase [ [cited by applicant]
U.S. Appl. No. 17/986,618, filed Nov. 14, 2022, Raj et al. [cited by applicant]
Skripnyuk A.A., et al.; “Modern methods for producing beta-galactosidase”; Science Innovations Technologies, 3; 2014; pp. 198-204. [cited by applicant]
Office Action issued on Jan. 22, 2021, in U.S. Appl. No. 16/998,706 (US 2021-0032615). [cited by applicant]
U.S. Appl. No. 16/604,129, filed Oct. 9, 2019, Raj et al. [cited by applicant]
U.S. Appl. No. 16/604,133, filed Oct. 9, 2019, Raj et al. [cited by applicant]
“UNIPROT: A0AOB5J47” (Apr. 1, 2015), Retrieved from the Internet, URL:http://ibis/exam/dbfetch.jsp?id=UNIPROT:A0A0B5J47 (Retrieved on May 11, 2017). [cited by applicant]
“UNIPROT: A0AS2MCC8—beta galactosidase,” (Feb. 17, 2016) Retrieved from the Internet, URL: https://ibis/exam/dbfetch.jsp?id=UNIPROT:A0AOS2MCC8 [retrieved on Mar. 9, 2018). [cited by applicant]
Horner et al., “β-Galactosidase activity of commercial lactase samples in raw and pasteurized milk at refrigerated temperatures,” J. Dairy Sci. 94: 3242-3249 (2011). [cited by applicant]
Nakagawa et al., “Overexpression and functional analysis of cold-active β-galactosidase from Arthrobacter psychrolocatohilus strain F2,” Protein Expression and Purification 54 (2007) 295-299 (Available on line Mar. 2007… [cited by applicant]
Palak-Szukalska et al., “A novel cold-active β-D-galactosidase with transglycosylation activity from the [cited by applicant]
Schmidt et al., “Identification, cloning and expression of a cold-active β-galactosidase from a novel Arctic bacterium, Alkalilactibacillus ikkense,” (2010) Environmental Technology, 31:10, 1107-1114 (Published online J… [cited by applicant]
Wang et al., “A novel cold-adapted β-galactosidase isolated from [cited by applicant]
Wierzbicka-Wos et al., “A novel cold-active β-D-galactosidase from the [cited by applicant]
GenBank Accession No. CAI98003.1. [cited by applicant]
Kreft et al., “Lactose hydrolysing ability of sonicated cultures of [cited by applicant]
Office Action issued on Apr. 12, 2022 in U.S. Appl. No. 16/998,706 (US 2021-0032615). [cited by applicant]
Office Action issued on Apr. 29, 2022 in U.S. Appl. No. 16/604,129 (US 2021-0355471). [cited by applicant]
Rhimi et al., “Exploring the acidotolerance of B-galactosidase from [cited by applicant]
UniProt Accession No. F0K2P6, May 3, 2011. [cited by applicant]
UniProt Accession No. G6F860, Jan. 25, 2012. [cited by applicant]
Database GenBank: ACE06986.1, (Jun. 8, 2012). [cited by applicant]
Database GenBank: CDR82630.1, (Jun. 11, 2014). [cited by applicant]
UniProtKB—A0A076JKA5 (A0A076JKA5_BIFAD); Oct. 29, 2014; 7 pages. [cited by applicant]
UniProtKB—A0A0A1GLP4 (A0A0A1GLP4_BIFLN); Feb. 4, 2015; 8 pages. [cited by applicant]
UniProtKB—A0A0A715K5 (A0A0A715K5_9BIFI); Mar. 4, 2015; 8 pages. [cited by applicant]
UniProtKB—A0A0H2P357 (A0A0H2P357_BIFBI); Sep. 16, 2015; 7 pages. [cited by applicant]
UniProtKB—A0AOU5FVZ6 (A0A0U5FVZ6_LACDE); Mar. 16, 2016; 9 pages. [cited by applicant]
UniProtKB—A0A126SWK6 (A0A126SWK6_9BIFI); Jul. 6, 2016; 8 pages. [cited by applicant]
UniProtKB—A0A174BAQ4 (A0A174BAQ4_9BIFI); Sep. 7, 2016; 8 pages. [cited by applicant]
UniProtKB—A0A174BB61 (A0A174BB61_BIFAD); Sep. 7, 2016; 8 pages. [cited by applicant]
UniProtKB—A0A174BH17 (A0A174BH17_9FIRM); Sep. 7, 2016; 5 pages. [cited by applicant]
UniProtKB—A0A1D7UM07 (A0A1D7UM07_BIFLN); Jan. 18, 2017; 8 pages. [cited by applicant]
UniProtKB—A0A1D7ZXL7 (A0A1D7ZXL7_LIMFE); Jan. 18, 2017; 7 pages. [cited by applicant]
UniProtKB—A0A1S2W2V3 (A0A1S2W2V3_BIFLN); Apr. 12, 2017; 8 pages. [cited by applicant]
UniProtKB—A0A1X2Z956 (A0A1X2Z956_BIFAD); Jul. 5, 2017; 8 pages. [cited by applicant]
UniProtKB—A0A1X2ZA47 (A0A1X2ZA47_BIFAD); Jul. 5, 2017; 7 pages. [cited by applicant]
UniProtKB—A0A1X2ZAP4 (A0A1X2ZAP4_BIFAD); Jul. 5, 2017; 7 pages. [cited by applicant]
UniProtKB—A0A2G5Q4A6 (A0A2G5Q4A6_9BIFI); Jan. 31, 2018; 8 pages. [cited by applicant]
UniProtKB—A0A4ROSL12 (A0A4ROSL12_BIFLN); Jul. 31, 2019; 8 pages. [cited by applicant]
UniProtKB—A0A4ROU1N4 (A0A4ROU1N4_BIFLN); Jul. 31, 2019; 8 pages. [cited by applicant]
UniProtKB—A0A6A2R535 (A0A6A2R535_BIFAD); Jun. 17, 2020; 7 pages. [cited by applicant]
UniProtKB—A0A6B1X5Q7 (A0A6B1X5Q7_9BIFI); Jun. 17, 2020; 6 pages. [cited by applicant]
UniProtKB—A0A6|1DQE1 (A0A6|1DQE1_BIFLN); Aug. 12, 2020; 8 pages. [cited by applicant]
UniProtKB—A0A6L4K944 (A0A6L4K944_BIFAD); Oct. 7, 2020; 7 pages. [cited by applicant]
UniProtKB—A0A6L4V5B5 (A0A6L4V5B5_9BIFI); Oct. 7, 2020; 8 pages. [cited by applicant]
UniProtKB—A0A7D9N5G4 (A0A7D9N5G4_LACJH); Dec. 2, 2020; 8 pages. [cited by applicant]
UniProtKB—A0A829LWJ6 (A0A829LWJ6_LIMFE); Sep. 29, 2021; 7 pages. [cited by applicant]
UniProtKB—A5VKG8 (A5VKG8_LIMRD); Jul. 10, 2007; 8 pages. [cited by applicant]
UniProtKB—B2GAA1 (B2GAA1_LIMF3); Jun. 10, 2008; 7 pages. [cited by applicant]
UniProtKB—B2GAA2 (B2GAA2_LIMF3); Jun. 10, 2008; 6 pages. [cited by applicant]
UniProtKB—D6ZY97 (D6ZY97_BIFLJ); Aug. 10, 2010; 8 pages. [cited by applicant]
UniProtKB—E4SLB1 (E4SLB1_LACAR); Feb. 8, 2011; 8 pages. [cited by applicant]
UniProtKB—E8MRV2 (E8MRV2_BIFL1); Apr. 5, 2011; 8 pages. [cited by applicant]
UniProtKB—F0HTF8 (F0HTF8_LACDL); May 3, 2011; 9 pages. [cited by applicant]
UniProtKB—F0TG75 (F0TG75_LACAM); May 3, 2011; 8 pages. [cited by applicant]
UniProtKB—F2M1D8 (F2MID8_LACAL); May 11, 2011; 8 pages. [cited by applicant]
UniProtKB—F4AFP0 (F4AFP0_LACJH); Jun. 28, 2011; 8 pages. [cited by applicant]
UniProtKB—F8ASA8 (F8ASA8_BIFLN); Sep. 21, 2011; 8 pages. [cited by applicant]
UniProtKB—G6F860 (G6F860_LACDE); Jan. 25, 2012; 9 pages. [cited by applicant]
UniProtKB—13WJ66 (13WJ66_BIFBI); Sep. 5, 2012; 8 pages. [cited by applicant]
UniProtKB—K215J0 (K215J0_BIFBI); Nov. 28, 2012; 8 pages. [cited by applicant]
UniProtKB—Q5FJD5 (Q5FJD5_LACAC); Mar. 1, 2005; 9 pages. [cited by applicant]
UniProtKB—Q74KL4 (Q74KL4_LACJO); Jul. 5, 2004; 8 pages. [cited by applicant]
UnitProtKB—D9ZDZ1 (D9ZDZ1_9ZZZZ); Oct. 5, 2010; 7 pages. [cited by applicant]
Guo et al., “Protein tolerance to random amino acid change,” PNAS, vol. 101, No. 25, pp. 9205-9210 (Jun. 2004). [cited by applicant]
Keskin et al., “A new, structurally nonredundant, diverse data set of protein-protein interfaces and its implications,” Protein Science, vol. 13, pp. 1043-1055 (2004). [cited by applicant]
Klimova E.V. Advantages of using beta-galactosidase for hydrolysis of lactose and obtaining galactooligosaccharides; prospects for the use of the obtained products in industrial food technologies, Food and processing in… [cited by applicant]
Ogurtsov A.N., Methods of bioinformatic analysis, Textbook, Kharkov, 2011, NTU “KhPI”, pp. 4-5, 25. [cited by applicant]
Singer et al., “Genes & Genomes, A changing Perspective,” University Science Books Mill Valley, CA (1998). [cited by applicant]
UniProt Accession Nos. TrEMBL, A7A6G3_BIFAD, Sep. 11, 2007, Q38UW6_LACSS, 22.11.2005, Q38UW7_LACSS, 22.11.2005, R5YYAO_9LACO, Jul. 24, 2013, FOTG79_LACAM, May 3, 2011, K2MWD3_BIFBI, Nov. 28, 2012, D4QFE8_BIFBI, Jul. 15,… [cited by applicant]
Office Action and Search Report issued on May 14, 2021 in Russian Application No. 2019134223/10. [cited by applicant]
U.S. Appl. No. 17/285,288, filed Apr. 14, 2021, Hans Raj et al. [cited by applicant]
Banerjee, Goutam et al.; “Is divalent magnesium cation the best cofactor for bacterial β- galactosidase?”; J Biosci, vol. 43, No. 5; Oct. 4, 2018; pp. 941-945. [cited by applicant]
Kuznetsova, E., “Brackets in Text of Legal Document as a Linguistic and Cognitive Phenomenon”; Institute of Humanities, Severodvinsk branch of Lomonosov Northern (Arctic) Federal University; Vestnik Moskovskogo gosudars… [cited by applicant]
Nguyen, Thao Thi et al.; “Effect of mutations to amino acid A301 and F361 in thermostability and catalytic activity of the β-galactosidase from [cited by applicant]
Patent Office of the Russian Federation: Federal Institute of Industrial Property; Office Action (Enquiry); Russian Patent Application No. 2021112325/10(026315) (English translation); Jun. 19, 2023; 10 pages. [cited by applicant]
Seffernick, Jennifer et al.; “Melamine Deaminase and Atrazine Chlorohydrolase: 98 Percent Identical but Functionally Different”; Journal of Bacteriology, vol. 183, No. 8; Apr. 2001; pp. 2405-2410. [cited by applicant]
Whisstock, James C. et al.; “Prediction of protein function from protein sequence and structure”; Quarterly Review of Biophysics 36, 3; Aug. 2003; pp. 307-340. [cited by applicant]
“Beta-galactosidase [Bifidobacterium angulatum]”; NCBI Reference Sequence: WP_033508907.1; NCBI; https://www.ncbi.nlm.nih.gov/protein/WP_033508907.1?report=genbank&log$=prottop&blast_rank=1&RID=STY73TRP013; Nov. 7, 2014… [cited by applicant]
“Beta-galactosidase [Bifidobacterium bifidum]”; NCBI Reference Sequence: ALE11829.1; NCBI; https://www.ncbi.nlm.nih.gov/protein/ALE11829.1?report=genbank&log$=prottop&blast_rank=1&RID=STXB9JWN016; Sep. 14, 2015; 2 pages. [cited by applicant]
“Beta-galactosidase [Bifidobacterium longum]”; NCBI Reference Sequence: WP_013582379.1; NCBI; https://www.ncbi.nlm.nih.gov/protein/WP_013582379.1?report=genbank&log$=prottop&blast_rank=1&RID=STXT9S92016; May 18, 2013; 1… [cited by applicant]
“Beta-galactosidase [Lactobacillus amylovorus]”; NCBI Reference Sequence: WP_013438360.1; NCBI; https://www.ncbi.nlm.nih.gov/protein/WP_013438360.1?report=genbank&log$=prottop&blast_rank=1&RID=STWKFN82013; May 18, 2013;… [cited by applicant]
“Beta-galactosidase [Lactobacillus helveticus]”; NCBI Reference Sequence: KRO12099.1; NCBI; https://www.ncbi.nlm.nih.gov/protein/KRO12099.1?report=genbank&log$=prottop&blast_rank=1&RID=STXF1W9301N; Nov. 6, 2015; 2 pages. [cited by applicant]
“Beta-galactosidase [Limosilactobacillus reuteri]”; NCBI Reference Sequence: WP_003666991.1; NCBI; https://www.ncbi.nlm.nih.gov/protein/WP_003666991.1?report=genbank&log$=prottop&blast_rank=1&RID=STXX2K05013; Jul. 31, 2… [cited by applicant]
Odamaki, Toshitaka et al.; “Comparative Genomics Revealed Genetic Diversity and Species/Strain-Level Differences in Carbohydrate Metabolism of Three Probiotic Bifidobacterial Species”; International Journal of Genomics,… [cited by applicant]
UniProt—A0A174B8K1_BIFAD; Sep. 7, 2016; 6 pages. [cited by applicant]