Factors causing compositional changes in soy protein hydrolysates and effects on cell culture functionality.

Soy protein hydrolysates significantly enhance cell growth and recombinant protein production in cell cultures. The extent of this enhancement in cell growth and IgG production is known to vary from batch to batch. This can be due to differences in the abundance of different classes of compounds (e.g., peptide content), the quality of these compounds (e.g., glycated peptides), or the presence of specific compounds (e.g., furosine). These quantitative and qualitative differences between batches of hydrolysates result from variation in the seed composition and seed/meal processing. Although a considerable amount of literature is available that describes these factors, this knowledge has not been combined in an overview yet. The aim of this review is to identify the most dominant factors that affect hydrolysate composition and functionality. Although there is a limited influence of variation in the seed composition, the overview shows that the qualitative changes in hydrolysate composition result in the formation of minor compounds (e.g., Maillard reaction products). In pure systems, these compounds have a profound effect on the cell culture functionality. This suggests that the presence of these compounds in soy protein hydrolysates may affect hydrolysate functionality as well. This influence on the functionality can be of direct or indirect nature. For instance, some minor compounds (e.g., Maillard reaction products) are cytotoxic, whereas other compounds (e.g., phytates) suppress protein hydrolysis during hydrolysate production, resulting in altered peptide composition, and, thus, affect the functionality.

[1]  A. Matser,et al.  Origins of the poor filtration characteristics of wheat starch hydrolysates , 1998 .

[2]  W. Powrie,et al.  Mutagenic activity of pyrazine derivatives: a comparative study with Salmonella typhimurium, Saccharomyces cerevisiae and Chinese hamster ovary cells. , 1980, Food and cosmetics toxicology.

[3]  K. Shibasaki,et al.  Major proteins of soybean seeds. A straightforward fractionation and their characterization. , 1976, Journal of agricultural and food chemistry.

[4]  Juliet A. Gerrard,et al.  Protein–protein crosslinking in food: methods, consequences, applications , 2002 .

[5]  J. Orf,et al.  Protein and oil content of soybeans from different geographic locations , 1988 .

[6]  J. Bautista,et al.  Sunflower peptones: use as nitrogen source for the formulation of fermentation media , 1993 .

[7]  Mei Liu,et al.  Rational development of a serum-free medium and fed-batch process for a GS-CHO cell line expressing recombinant antibody , 2013, Cytotechnology.

[8]  R. L. Anderson,et al.  Compositional Changes in Trypsin Inhibitors, Phytic Acid, Saponins and Isoflavones Related to Soybean Processing , 1995 .

[9]  H. Katinger,et al.  Plant Protein Hydrolysates: Preparation of Defined Peptide Fractions Promoting Growth and Production in Animal Cells Cultures , 2000, Biotechnology progress.

[10]  R. Hayashi,et al.  DECREASED PROTEOLYSIS OF ALKALI-TREATED PROTEIN: CONSEQUENCES OF RACEMIZATION IN FOOD PROCESSING , 1980 .

[11]  F. Gòdia,et al.  Considerations on the lactate consumption by CHO cells in the presence of galactose. , 2006, Journal of biotechnology.

[12]  Nicholas E. Timmins,et al.  Metabolite profiling of CHO cells with different growth characteristics , 2012, Biotechnology and bioengineering.

[13]  J. Porres,et al.  The role of phytic acid in legumes: antinutrient or beneficial function? , 2000, Journal of Physiology and Biochemistry.

[14]  J. MacDonald,et al.  The composition of glyphosate-tolerant soybean seeds is equivalent to that of conventional soybeans. , 1996, The Journal of nutrition.

[15]  É. Varga-Visi,et al.  The effect of thermic treatment conditions on the amino acid composition of soybean and maize , 2009 .

[16]  A. Matser,et al.  Filtration characteristics of maize and wheat starch hydrolysates , 1998 .

[17]  H. Gruppen,et al.  The influence of screw configuration on the in vitro digestibility and protein solubility of soybean and rapeseed meals. , 1995 .

[18]  M. Berhow,et al.  Environmental influences on isoflavones and saponins in soybeans and their role in colon cancer. , 2005, The Journal of nutrition.

[19]  Michael Butler,et al.  Animal cell cultures: recent achievements and perspectives in the production of biopharmaceuticals , 2005, Applied Microbiology and Biotechnology.

[20]  K. Saio,et al.  Properties of soybean in model storage studies. , 1985 .

[21]  S. Rohn,et al.  Antioxidant activity of protein-bound quercetin. , 2004, Journal of agricultural and food chemistry.

[22]  J. Goergen,et al.  Peptide fractions of rapeseed hydrolysates as an alternative to animal proteins in CHO cell culture media , 2006 .

[23]  D. Jayme,et al.  Media formulation options and manufacturing process controls to safeguard against introduction of animal origin contaminants in animal cell culture , 2000, Cytotechnology.

[24]  M. M. Macmasters,et al.  Studies on soybean carbohydrates. , 1941 .

[25]  J. L. Cartter,et al.  Quantitative Interrelations of Protein and Nonprotein Constituents of Soybeans 1 , 1962 .

[26]  C. Prieto,et al.  Effect of sodium butyrate and zinc sulphate supplementation on recombinant human IFN-β production by mammalian cell culture , 2006 .

[27]  H. Katinger,et al.  Specific Effects of Synthetic Oligopeptides on Cultured Animal Cells , 2002, Biotechnology progress (Print).

[28]  H. Gruppen,et al.  In vitro accessibility of untreated, toasted, and extruded soybean meals for proteases and carbohydrases , 1997 .

[29]  S. Braun,et al.  State of the Art Manufacturing of Protein Hydrolysates , 2008 .

[30]  A. Can,et al.  Usage of xylose or glucose as non-enzymatic browning agent for reducing ruminal protein degradation of soybean meal , 2002 .

[31]  P. Bucheli,et al.  Comparison of Soluble Sugar Degradation in Soybean Seed under Simulated Tropical Storage Conditions , 1998 .

[32]  E. Austreng Digestibility determination in fish using chromic oxide marking and analysis of contents from different segments of the gastrointestinal tract , 1978 .

[33]  Konstantin Konstantinov,et al.  The use of peptones as medium additives for the production of a recombinant therapeutic protein in high density perfusion cultures of mammalian cells , 2000, Cytotechnology.

[34]  L. Wang Diatomaceous Earth Precoat Filtration , 2006 .

[35]  T. Gabryelak,et al.  Effect of the phytoestrogen, genistein‐8‐C‐glucoside, on Chinese hamster ovary cells in vitro , 2007, Cell biology international.

[36]  C. Grieshop,et al.  Chemical and nutritional characteristics of United States soybeans and soybean meals. , 2003, Journal of agricultural and food chemistry.

[37]  W. Wolf,et al.  Protease inhibitors in plant foods: content and inactivation. , 1986, Advances in experimental medicine and biology.

[38]  Z. Wen,et al.  Screening soy hydrolysates for the production of a recombinant therapeutic protein in commercial cell line by combined approach of near-infrared spectroscopy and chemometrics , 2013, Applied Microbiology and Biotechnology.

[39]  C. W. Hesseltine,et al.  Free fatty acids identified as antitryptic factor in soybeans fermented by Rhizopus oligosporus. , 1975, The Journal of nutrition.

[40]  F. Schwende,et al.  Lysinoalanine: presence in foods and food ingredients , 1975, Science.

[41]  R. J. Evans,et al.  HEAT INACTIVATION OF THE BASIC AMINO ACIDS AND TRYPTOPHAN , 1951 .

[42]  J. Goergen,et al.  Influence of the rapeseed protein hydrolysis process on CHO cell growth. , 2008, Bioresource technology.

[43]  M. Fussenegger,et al.  Survival Factor‐Like Activity of Small Peptides in Hybridoma and CHO Cells Cultures , 2008, Biotechnology progress.

[44]  S. H. Ashoor,et al.  Maillard Browning of Common Amino Acids and Sugars , 1984 .

[45]  P. Utterback,et al.  Chemical composition and nutritional quality of soybean meals prepared by extruder/expeller processing for use in poultry diets. , 2006, Journal of agricultural and food chemistry.

[46]  A. D. Krikorian,et al.  Inhibition of trypsin activity in vitro by phytate , 1982 .

[47]  I. Vaintraub,et al.  Effect of phytate on the in vitro activity of digestive proteinases , 1991 .

[48]  D. Knabe,et al.  Comparison of the Nutritive Value of Different Heat-Treated Commercial Soybean Meals: Utilization by Chicks in Practical Type Rations , 1986 .

[49]  R. Öste,et al.  Effect of Maillard reaction products on protein digestion. In vitro studies , 1986 .

[50]  P. Donahoe,et al.  Effect of E. Coli endotoxin on mammalian cell growth and recombinant protein production , 1990, In Vitro Cellular & Developmental Biology.

[51]  P. Sjödin,et al.  Effect of Maillard reaction products on protein digestion. In vivo studies on rats. , 1984, The Journal of nutrition.

[52]  M. de Vrese,et al.  Protein-bound D-amino acids, and to a lesser extent lysinoalanine, decrease true ileal protein digestibility in minipigs as determined with (15)N-labeling. , 2000, The Journal of nutrition.

[53]  Wil van Megen,et al.  The determination of trypsin inhibitor levels in foodstuffs. , 1980, Journal of the science of food and agriculture.

[54]  H. Haase,et al.  Functions of zinc in signaling, proliferation and differentiation of mammalian cells , 2001, Biometals.

[55]  A. C. Eldridge Determination of isoflavones in soybean flours, protein concentrates, and isolates , 1982 .

[56]  J. A. Thomas,et al.  A review of 5-hydroxymethylfurfural (HMF) in parenteral solutions. , 1984, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[57]  P. Price,et al.  Benefits and Limitations of Protein Hydrolysates as Components of Serum-Free Media for Animal Cell Culture Applications , 2008 .

[58]  J. Boye,et al.  Composition and Functional Properties of Soy Protein Isolates Prepared Using Alternative Defatting and Extraction Procedures , 2006 .

[59]  Y. Hua,et al.  Oxidative modification of soy protein by peroxyl radicals. , 2009 .

[60]  F. Wolf,et al.  Cell (patho)physiology of magnesium. , 2008, Clinical science.

[61]  Kevin A Cockell,et al.  Effects of antinutritional factors on protein digestibility and amino acid availability in foods. , 2005, Journal of AOAC International.

[62]  H. Eagle,et al.  The utilization of carbohydrates by human cell cultures. , 1958, The Journal of biological chemistry.

[63]  L. Stegink,et al.  Excessive urinary zinc losses during parenteral alimentation. , 1975, The Journal of surgical research.

[64]  M. Antoniewicz,et al.  Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. , 2011, Metabolic engineering.

[65]  C. Parsons,et al.  Effect of heating on nutritional quality of conventional and Kunitz trypsin inhibitor-free soybeans. , 1992, Poultry science.

[66]  H. Swaisgood,et al.  Syntheses and digestibility determination of some epimeric tripeptides occurring in dietary proteins , 1985 .

[67]  R. Oste Effect of Maillard reaction products on protein digestion. , 1989, Progress in clinical and biological research.

[68]  H. Babich,et al.  Comparative cytotoxicities of selected minor dietary non-nutrients with chemopreventive properties. , 1993, Cancer letters.

[69]  Y. Schneider,et al.  Fortification of a protein-free cell culture medium with plant peptones improves cultivation and productivity of an interferon-γ-producing CHO cell line , 2003, In Vitro Cellular & Developmental Biology - Animal.

[70]  J. Finley,et al.  Heat and alkaline damage to proteins: racemization and lysinoalanine formation , 1984 .

[71]  G Stephanopoulos,et al.  Metabolism of peptide amino acids by Chinese hamster ovary cells grown in a complex medium. , 1999, Biotechnology and bioengineering.

[72]  J. Maga Lysinoalanine in foods , 1984 .

[73]  Gruppen,et al.  Inactivation Kinetics Study of the Kunitz Soybean Trypsin Inhibitor and the Bowman-Birk Inhibitor. , 1998, Journal of agricultural and food chemistry.

[74]  S. Rohn,et al.  In vitro inhibition of α-chymotryptic activity by phenolic compounds , 2001 .

[75]  H. Swaisgood,et al.  Further studies on in vitro digestibility of some epimeric tripeptides , 1987 .

[76]  U. Cogan,et al.  Isolation of soybean protein: Effect of processing conditions on yields and purity , 1967 .

[77]  H. Eagle THE SPECIFIC AMINO ACID REQUIREMENTS OF A HUMAN CARCINOMA CELL (STRAIN HELA) IN TISSUE CULTURE , 1955, The Journal of experimental medicine.

[78]  Binding of copper(II) and other metal ions by lysinoalanine and related compounds and its significance for food safety , 1988 .

[79]  J. Cook,et al.  Inhibitory effect of a soybean-protein--related moiety on iron absorption in humans. , 1994, The American journal of clinical nutrition.

[80]  N. Chung,et al.  Usability of size-excluded fractions of soy protein hydrolysates for growth and viability of Chinese hamster ovary cells in protein-free suspension culture. , 2007, Bioresource technology.

[81]  M. B. Parker,et al.  Chemical composition and lipoxygenase activity in soybeans as affected by genotype and environment , 1976, Journal of the American Oil Chemists' Society.

[82]  V. Ravindran,et al.  Phytate and phytase: consequences for protein utilisation , 2000, Nutrition Research Reviews.

[83]  I. Liener,et al.  Heat inactivation of the Kunitz and Bowman-Birk soybean protease inhibitors , 1989 .

[84]  Kenji Watanabe,et al.  Effects of soybean saponins on chymotryptic hydrolyses of soybean proteins , 1998 .

[85]  D. E. Alden Soy processing: From beans to ingredients , 1975 .

[86]  F. Laborda,et al.  Composition and characterization of soyabean and related products. , 1997, Critical reviews in food science and nutrition.

[87]  M. W. Kearsley,et al.  Saponin content of soya and some commercial soya products by means of high‐performance liquid chromatography of the sapogenins , 1986 .

[88]  G. Mittal,et al.  Saponins from edible legumes: chemistry, processing, and health benefits. , 2004, Journal of medicinal food.

[89]  P. A. Kemme,et al.  Interaction between protein, phytate, and microbial phytase. In vitro studies. , 2006, Journal of agricultural and food chemistry.

[90]  J. Mauron Influence of processing on protein quality. , 1985, Bibliotheca nutritio et dieta.

[91]  W. Thilly,et al.  High density mammalian cell growth in Leibovitz bicarbonate-free medium: effects of fructose and galactose on culture biochemistry. , 1985, Journal of cell science.

[92]  C. Guzmán,et al.  Seed composition of soybean cultivars evaluated in different environmental regions , 1998 .

[93]  S. Rohn,et al.  Reactions of Plant Phenolics with Food Proteins and Enzymes under Special Consideration of Covalent Bonds , 2003 .

[94]  M. Friedman,et al.  Racemization kinetics of amino acid residues in alkali-treated soybean protein , 1985 .

[95]  P. Morrissey,et al.  Nutritional and toxicological aspects of the Maillard browning reaction in foods. , 1989, Critical reviews in food science and nutrition.

[96]  R. C. Parker,et al.  Nutrition of Animal Cells in Tissue Culture. I. Initial Studies on a Synthetic Medium.∗,† , 1950, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[97]  R. Klebe,et al.  Biochemical selection systems for mammalian cells: The essential amino acids , 1976, Somatic cell genetics.

[98]  K. Hashimoto,et al.  Effect of Overprocessing on Availability of Amino Acids and Energy in Soybean Meal , 1992 .

[99]  Gregory Stephanopoulos,et al.  Metabolic Flux Analysis , 2014 .

[100]  A. R. Costa,et al.  Comparison of commercial serum-free media for CHO-K1 cell growth and monoclonal antibody production. , 2012, International journal of pharmaceutics.

[101]  D. Knabe,et al.  Effects of different heat treatments during processing on nutrient digestibility of soybean meal in growing swine. , 1987, Journal of animal science.

[102]  V. Tufarelli,et al.  Pea (Pisumsativum L.) Seeds as an Alternative Dietary Protein Source for Broilers: Influence on Fatty Acid Composition, Lipid and Protein Oxidation of Dark and White Meats , 2011 .

[103]  I. Chung,et al.  Variation in isoflavone of soybean cultivars with location and storage duration. , 2003, Journal of agricultural and food chemistry.

[104]  F. N. Reece,et al.  Relationships Between Color, Trypsin Inhibitor Contents, and Urease Index of Soybean Meal and Effects on Broiler Performance , 1981 .

[105]  M. Sugano,et al.  Effect of Soy and Milk Whey Protein Isolates and Their Hydrolysates on Weight Reduction in Genetically Obese Mice , 2000, Bioscience, biotechnology, and biochemistry.

[106]  Å. Krogdahl,et al.  Soybean proteinase inhibitors affect intestinal trypsin activities and amino acid digestibilities in rainbow trout (Oncorhynchus mykiss) , 1994 .

[107]  C. Tsukamoto,et al.  Factors affecting isoflavone content in soybean seeds: changes in isoflavones, saponins, and composition of fatty acids at different temperatures during seed development , 1995 .

[108]  S. Vaughn,et al.  Characterization and antimutagenic activity of soybean saponins. , 2000, Mutation research.

[109]  Nielsen,et al.  Chemical and Sensory Characterization of Hydrolyzed Vegetable Protein, a Savory Flavoring. , 1998, Journal of agricultural and food chemistry.

[110]  A. Demain,et al.  Protein hydrolysates in biotechnology , 2010 .

[111]  Å. Krogdahl,et al.  Soybean trypsin inhibitors in diets for Atlantic salmon (Salmo salar, L): effects on nutrient digestibilities and trypsin in pyloric caeca homogenate and intestinal content. , 1994, Comparative biochemistry and physiology. Part A, Physiology.

[112]  K. Pierce,et al.  Development toward rapid and efficient screening for high performance hydrolysate lots in a recombinant monoclonal antibody manufacturing process , 2012, Biotechnology progress.

[113]  George C. Fahey,et al.  Chemical composition and protein quality comparisons of soybeans and soybean meals from five leading soybean-producing countries. , 2004 .

[114]  T. Matsuda,et al.  Maillard reaction of disaccharides with protein suppressive effect of nonreducing end pyranoside groups on browning and protein polymerization , 1989 .

[115]  Y. Schneider,et al.  Characterisation of beneficial and detrimental effects of a soy peptone, as an additive for CHO cell cultivation , 2011 .

[116]  H. Gardner Lipid hydroperoxide reactivity with proteins and amino acids: a review , 1979 .

[117]  W. Powrie,et al.  A comparative genotoxicity study of chlorogenic acid (3-0-caffeoylquinic acid). , 1981, Mutation research.

[118]  D. Dorrell Chlorogenic Acid Content of Meal from Cultivated and Wild Sunflowers 1 , 1976 .

[119]  V. Prakash,et al.  Extractability of polyphenols of sunflower seed in various solvents , 1982, Journal of Biosciences.

[120]  W. Kwolek,et al.  Soybean isoflavones: effect of environment and variety on composition. , 1983, Journal of agricultural and food chemistry.

[121]  F Gòdia,et al.  Improvement of CHO Cell Culture Medium Formulation: Simultaneous Substitution of Glucose and Glutamine , 2000, Biotechnology progress.

[122]  Christopher P. Marquis,et al.  Development of Super‐CHO protein‐free medium based on a statistical design , 2007 .

[123]  M. Boekel,et al.  A review of Maillard reaction in food and implications to kinetic modelling , 2000 .

[124]  D. Dornbos,et al.  Soybean seed protein and oil contents and fatty acid composition adjustments by drought and temperature , 1992 .

[125]  J. Bada,et al.  Diketopiperazine formation during investigations of amino Acid racemization in dipeptides. , 1981, Science.

[126]  A. Wouwer,et al.  A detailed metabolic flux analysis of an underdetermined network of CHO cells. , 2010, Journal of biotechnology.

[127]  K. Morihara,et al.  Comparative specificity of microbial acid proteinases for synthetic peptides. II. Effect of secondary interaction. , 1973, Archives of biochemistry and biophysics.

[128]  P. Morrissey,et al.  Metal ion complexation by products of the Maillard reaction , 1997 .

[129]  Guoxiang Chen,et al.  Combined approach of NMR and chemometrics for screening peptones used in the cell culture medium for the production of a recombinant therapeutic protein. , 2007, Biotechnology and bioengineering.

[130]  Yan Zhou,et al.  Effects of peptone on hybridoma growth and monoclonal antibody formation , 2004, Cytotechnology (Dordrecht).

[131]  A. Rani,et al.  Influence of growing environment on the biochemical composition and physical characteristics of soybean seed , 2006 .

[132]  Harry Gruppen,et al.  Chemometric analysis of soy protein hydrolysates used in animal cell culture for IgG production - An untargeted metabolomics approach , 2014 .

[133]  Y. Schneider,et al.  Effects of a soy peptone on γ-IFN production steps in CHO-320 cells , 2011 .

[134]  Y. Ghali,et al.  The effect of environmental conditions on the chemical composition of soybean seeds: Relationship between the protein, oil, carbohydrate and trypsin inhibitor content , 1988 .