Dipeptides in nutrition and therapy: cyanophycin-derived dipeptides as natural alternatives and their biotechnological production

Springer Science and Business Media LLC - Tập 87 - Trang 815-828 - 2010
Ahmed Sallam1, Alexander Steinbüchel2
1Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms-Universität Münster, Münster, Germany
2Institut für Molekulare Mikrobiologie und Biotechnologie, Westfälische Wilhelms Universität Münster, Münster, Germany

Tóm tắt

The numerous physiological functions of the nonessential amino acid L-aspartate, the semi-essential amino acid L-arginine, and the essential amino acid L-lysine, made them attractive for a wide range of nutritional and/or therapeutic applications. Furthermore, the administration of these amino acids as mixtures or as dipeptides for higher bioavailability is scientifically approved, and various commercial products of these forms are already available on the market. Although the industrial production of dipeptides is, with few exceptions, in an early stage, several strategies have been established and are compared in this review. Additionally, the recent developments in the technical production of aspartate–arginine and aspartate–lysine dipeptides from the biopolymer cyanophycin produced in microorganisms are discussed. Cyanophycin-derived dipeptides are produced exclusively by biotechnological procedures, probably possess higher bioavailability and may be used as better alternatives to the widely applied amino acid mixtures. Thus, the pivotal advantages and the potential applications of these dipeptides as well as of their constituting amino acids in nutrition and therapy are also discussed. Special emphasis is dedicated to arginine due to its numerous physiological roles in many cardiovascular, genitourinary, gastrointestinal, and immune disorders.

Tài liệu tham khảo

Ahmed I, Khan MA (2004) Dietary arginine requirement of fingerling Indian major carp, Cirrhinus mrigala (Hamilton). Aquac Nutr 10:217–225 Appleton J (2002) Arginine: clinical potential of a semi-essential amino acid. Altern Med Rev 7:512–522 Barbul A, Lazarou SA, Efron DT, Wasserkrug HL, Efron G (1990) Arginine enhances wound healing and lymphocyte immune responses in humans. Surgery 108:331–336 Bendik FT, Lee KJ, Zhang Y, Failla M, Dabrowski K (2006) Optimization of dipeptide–protein mixtures in experimental diet formulations for rainbow trout (Oncorhynchus mykiss) alevins. Aquaculture 254:517–525 Berg H (2003) Untersuchungen zu Funktion und Struktur der Cyanophycin-Synthetase von Anabaena variabilis ATCC 29413. Dissertation. Humboldt–Universität zu Berlin, Germany Besset A, Bonardet A, Rondouin G, Descomps B, Passouant P (1982) Increase in sleep related GH and Prl secretion after chronic arginine aspartate administration in man. Acta Endocrinol 99:18–23 Biegel A, Knütter I, Hartrodt B, Gebauer S, Theis S, Luckner P, Kottra G, Rastetter M, Zebisch K, Thondorf I, Daniel H, Neubert K, Brandsch M (2006) The renal type H1=peptide symporter PEPT2: structure–affinity relationships. Amino Acids 31:137–156 Boutard V, Havouis R, Fouqueray B, Philippe C, Moulinoux JP, Baud L (1995) Transforming growth factor-beta stimulates arginase activity in macrophages. Implications for the regulation of macrophage cytotoxicity. J Immunol 155:2077–2084 Brandsch M, Knütter I, Leibach FH (2004) The intestinal H+/peptide symporter PEPT1: structure–affinity relationships. Eur J Pharm Sci 21:53–60 Burtscher M, Brunner F, Faulhaber M, Hotter B, Likar R (2005) The prolonged intake of l-arginine-l-aspartate reduces blood lactate accumulation and oxygen consumption during submaximal exercise. J Sports Sci Med 4:314–322 Chibata IT, Kakimoto J, Kato J (1965) Enzymatic production of l-alanine by Pseudomonas dacunhae. Appl Microbiol 13:638–645 Christianson DW (2005) Arginase: structure, mechanism, and physiological role in male and female sexual arousal. Acc Chem Res 38:191–201 Cynober LA (2003) Metabolic and therapeutic aspects of amino acids in clinical nutrition, 2nd edn. CRC Press LLC, Boca Raton Daniel H, Spanier B, Kottra G, Weitz D (2006) From bacteria to man: Archaic proton-dependent peptide transporters at work. Physiology 21:93–102 De-Aloysio D, Mantuano R, Mauloni M, Nicoletti G (1982) The clinical use of arginine aspartate in male infertility. Acta Eur Fertil 13:133–167 Dean W, Pryor K (2001) Growth hormone: amino acids as GH secretagogues—a review of the literature. Vit Res News. Available at http://www.vrp.com (accessed Feb. 2010) Dock DB, Aguilar-Nascimento JE, Latorraca MQ (2004) Probiotics enhance the recovery of gut atrophy in experimental malnutrition. Biocell 28:143–150 Doekel S, Marahiel MA (2000) Dipeptide formation on engineered hybrid peptide synthetases. Chem Biol 7:373–384 Duruy A (1968) Expertise clinique de l´aspartate d´arginine. Med Int 1:203 Elsair C (1985) Effets de l’arginine, administrie par voie orale. C R Soc Biol 179:608–611 Flodin NW (1997) The metabolic roles, pharmacology, and toxicology of lysine. J Am Coll Nutr 16:7–21 Geueke B, Kohler HP (2007) Bacterial beta-peptidyl aminopeptidases: on the hydrolytic degradation of beta-peptides. Appl Microbiol Biotechnol 74:1197–1204 Glansdorff N, Xu Y (2007) Microbial arginine biosynthesis: pathway, regulation and industrial production. In: Wendisch VF (ed) Amino acid biosynthesis-pathways, regulation and metabolic engineering, vol 5, Microbiology Monographs. Springer, Berlin, pp 219–258 Gusyatiner MM, Leonova TV, Ptitsyn LR, Yampolskaya TA (2005) l-Arginine producing Escherichia coli and method of producing l-arginine. US Patent 6841365 Hrabak A, Bajor T, Temesi A, Meszaros G (1996) The inhibitory effect of nitrite, a stable product of nitric oxide (NO) formation, on arginase. FEBS Lett 390:203–206 Hurson M, Regan MC, Kirk SJ, Wasserkrug HL, Barbul A (1995) Metabolic effects of arginine in a healthy elderly population. J Parenter Enteral Nutr 19:227–230 Isidori A, Lo-Monaco A, Cappa M (1981) A study of growth hormone release in man after oral administration of amino acids. Curr Med Res Opin 7:475–481 Kernohan AFB, McIntyre M, Hughes DM, Tam SW, Worcel M, Reid JL (2004) An oral yohimbine/l-arginine combination (NMI 861) for the treatment of male erectile dysfunction: a pharmacokinetic, pharmacodynamic and interaction study with intravenous nitroglycerine in healthy male subjects. Br J Clin Pharmacol 59:85–93 Kihlberg R (1972) The microbe as a source of food. Annu Rev Microbiol 26:427–466 Kim YS, Kim YW, Birtwhis W (1972) Peptide hydrolases in brush border and soluble fractions of small intestinal mucosa of rat and man. J Clin Invest 51:1419–1430 Kircheis G, Nilius R, Held C, Berndt H, Buchner M, Gortelmeyer R, Hendricks R, Krüger B, Kuklinski B, Meister H, Otto H, Rink C, Rösch W, Stauch S (1997) Therapeutic efficacy of l-ornithine-l-aspartate infusions in patients with cirrhosis and hepatic encephalopathy: results of a placebo-controlled, doubleblind study. Hepatology 25:1351–1360 Kleinberg I (1980) Means and method for improving defenses against caries. US Patent 4225579 Laidlaw SA, Kopple JD (1987) Newer concepts of the indispensable amino acids. Am J Clin Nutr 46:593–605 Lamm S, Schönlau F, Rohdewald P (2003) Prelox® for improvement of erectile function: a review. Eur Bull Drug Res 11:29–37 Leonard JV, Marrs TC, Addison JM, Burston D, Clegg KM, Lloyd JK, Matthews DM, Seakins JW (1976) Intestinal absorption of amino acids and peptides in Hartnup disorder. Pediatr Res 10:246–249 Li F, Yu G, Li S, Peng S, Fu J, Wu D (2002) An antimetastatic study of Arg-Asp (RD) on salivary adenoid cystic carcinoma in vivo. Chin J Stomatol 37:87–89 Macintyre JG (1987) Growth hormone and athletes. Sports Med 4:129–142 Mansart A, Bollaert P, Levy B, Nicolas M, Mallié J (2003) Comparative effects of dexamethasone and l-canavanine in experimental septic shock. Eur J Pharmacol 475:61–67 Meredith JW, Ditesheim JA, Zaloga G (1990) Visceral protein levels in trauma patients are greater with peptide diet than with intact protein diet. J Trauma 30:825–828 Merrifield R (1963) Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85:2149–2154 Modolell M, Corraliza IM, Link F, Soler G, Eichmann K (1995) Reciprocal regulation of the nitric oxide synthase/arginase balance in mouse bone marrow-derived macrophages by TH1 and TH2 cytokines. Eur J Immunol 25:1101–1104 Mooibroek H, Osterhuis N, Giuseppin M, Toonen M, Franssen H, Scott E, Sanders J, Steinbüchel A (2007) Assessment of technological options and economical feasibility for cyanophycin biopolymer and high-value amino acid production. Appl Microbiol Biotechnol 77:257–267 Morelle JV, Lauzanne-Morelle EMT (1984) Derivatives of lysine and aspartic acid. US Patent 4447366 Nagayasu T, Miyanaga M, Tanaka T, Sakiyama T, Nakanishi K (1994) Synthesis of aspartame precursor with an immobilized thermolysin in tert-amy1 alcohol. Biotechnol Bioeng 43:1118–1123 Neumann K, Stephan DP, Ziegler K, Hühns M, Broer I, Lockau W, Pistorius EK (2005) Production of cyanophycin, a suitable source for the biodegradable polymer polyaspartate, in transgenic plants. Plant Biotechnol J 3:249–258 Obst M, Krug A, Luftmann H, Steinbüchel A (2005) Degradation of cyanophycin by Sedimentibacter hongkongensis strain KI and Citrobacter amalonaticus strain G isolated from an anaerobic bacterium consortium. Appl Environ Microbiol 71:3642–3652 Oikawa T (2007) Alanine, aspartate, and asparagine metabolism in microorganisms. In: Wendisch VF (ed) Amino acid biosynthesis-pathways, regulation and metabolic engineering, vol 5, Microbiology Monographs. Springer, Berlin, pp 273–288 Radha C, Govindaraju K, Kany TCS, Tiku PK, Singh SA, Gowda LR, Swamylingappa B, Rao ARG, Prakash V, Ramasarma PR (2006) Process for the preparation of high arginine peptides. US Patent 7091001 Rohdewald P, Ferrari V (2004) Attaining sexual wellness and health of the sexual vascular system with proanthocyanidins. Patent Application 2004137081. Ross E, Dominy W (1990) The nutritional value of dehydrated, blue-green algae (Spirulina platensis) for poultry. Poult Sci 69:794–800 Ruey JYu, Van Scott EJ (2008) Compositions and therapeutic use of N-acetyl aldosamines and N-acetylamino acids. Patent Application 20080214649 Sakanyan V, Marc F, Hovsepyan A, Lecocq M (2005) Microorganisms and method for l-arginine production by fermentation. US Patent 6897048 Sallam A, Steinbüchel A (2009a) Biotechnological production of cyanophycin dipeptides. Patent Application PCT/EP2009/057382 Sallam A, Steinbüchel A (2009b) Cyanophycin-degrading bacteria in digestive tracts of mammals, birds and fish and consequences for possible applications of cyanophycin and its dipeptides in nutrition and therapy. J Appl Microbiol 107:474–484 Sallam A, Kast A, Przybilla S, Meiswinkel T, Steinbüchel A (2009) Biotechnological process for production of β-dipeptides from cyanophycin at technical scale and its optimization. Appl Environ Microbiol 75:29–38 Sánchez A, Rubano D, Shavlik GW, Hubbard R, Horning M (1998) Cholesterolemic effects of the lysine/arginine ratio in rabbits after initial early growth. Arch Latinoam Nutr 38:229–238 Schacter A, Friedman S, Goldman JA, Eckerling B (1973) Treatment of oligospermia with the amino acid arginine. Int J Gynaecol Obstet 11:206–209 Schellen TM, Declerq JA (1978) Arginine aspartate in the treatment of oligozoospermia. Dermatol Monschr 164:578–580 Schmid P, Gleispach H, Wolf W, Pessendorfer H, Schwaberger P (1980) Leistungsbeeinflussung und Stoffwechselveränderungen während einer Langzeitbelastung unter Argininaspartat. Leistungssport 10:486–495 Seebach D, Overhand M, Kühnle FNM, Martinoni B, Oberer L, Hommel U, Widmer H (1996) Β-Peptides: synthesis by Arndt–Eistert homologation with concomitant peptide coupling. Structure determination by NMR and CD spectroscopy and by X-ray crystallography. Helical secondary structure of a β-hexapeptide in solution and its stability towards pepsin. Helv Chim Acta 76:913–941 Sellier J (1979) Intéret de l´aspartate d´arginine sargenor chez des athletes de compétition en périod d´entrainement intensif. Rev Med Toulouse 5:879 Silk DBA, Perrett D, Clark ML (1975) Jejunal and ileal absorption of dibasic amino acids and an arginine-containing dipeptide in cystinuria. Gastroenterology 68:1426–1432 Sprenger GA (2007) Aromatic amino acids. In: Wendisch VF (ed) Amino acid biosynthesis-pathways, regulation and metabolic engineering, vol 5, Microbiology Monographs. Springer, Berlin, pp 93–128 Stanislavov R, Nikolova V (2003) Treatment of erectile dysfunction with Pycnogenol® and l-arginine. J Sex Marital Ther 29:207–213 Steel A, Nussberger S, Romero MF, Boron WF, Boyd CA, Hediger MA (1997) Stoichiometry and pH dependence of the rabbit proton-dependent oligopeptide transporter PepT1. J Physiol 498:563–569 Steinle A, Bergander K, Steinbüchel A (2009) Metabolic engineering of Saccharomyces cerevisiae towards novel cyanophycins with an extended range of constituents. Appl Environ Microbiol. doi:10.1128/AEM.00383-09 Suminski RR, Robertson RJ, Goss FL, Arslanian S, Kang J, DaSilva S, Utter AC, Metz KF (1997) Acute effect of amino acid ingestion and resistance exercise on plasma growth hormone concentration in young men. Int J Sport Nutr 7:48–60 Tanimura J (1967) Studies on arginine in human semen. Part II. The effects of medication with l-arginine-HCl on male infertility. Bull Osaka Med Sch 13:84–89 Tsuji A, Tamai I, Hirooka H, Terasaki T (1986) Β-Lactam antibiotics and transport via the dipeptide carrier system across the intestinal brush-border membrane. Biochem Pharmacol 36:565–567 Utagawa T (2004) Production of arginine by fermentation. J Nutr 134:2854–2857 Vodovotz Y, Bogdan C, Paik J, Xie Q-W, Nathan C (1993) Mechanisms of suppression of macrophage nitric oxide release by transforming growth factor. J Exp Med 178:605–613 Voet D, Voet JG (2004) Biochemistry, 3rd edn. John Wiley and Sons Inc., New York Voss I (2005). Optimierung der biotechnologischen Produktion von Cyanophycin in rekombinanten Stämmen von Ralstonia eutropha durch metabolic engineering. Dissertation, Westfälische Wilhelms-Universität, Münster, Germany Witte MB, Barbul A (2003) Arginine physiology and its implication for wound healing. Wound Repair Regen 11:419–423 Wittmann C, Becker J (2007) The l-lysine story: from metabolic pathways to industrial production. In: Wendisch VF (ed) Amino acid biosynthesis-pathways, regulation and metabolic engineering, vol 5, Microbiology Monographs. Springer, Berlin, pp 39–70 Yagasaki M, Hashimoto S (2008) Synthesis and application of dipeptides; current status and perspectives. Appl Microbiol Biotechnol 81:13–22 Yanni AE, Perrea DN, Yatzidis HA (2005) Effect of antiatherogenic l-aspartate and l-glutamate on serum lipoproteins cholesterol and apolipoproteins A-1 and B in rabbits fed with high cholesterol diet. Nutr Metab Cardiovasc Dis 15:161–165