Synthesis of l(-)-carnitine by hydration of crotonobetaine by enterobacteria

Springer Science and Business Media LLC - Tập 27 - Trang 538-544 - 1988
Hermann Seim1, Hans-Peter Kleber2
1Bereich Medizin, Institut für Pathologische Biochemie, Karl-Marx-Universität Leipzig, Leipzig
2Sektion Biowissenschaften, Bereich Biochemie, Karl-Marx-Universität Leipzig, Leipzig, German

Tóm tắt

Enterobacteria, especially Escherichia coli, Salmonella typhimurium and Proteus vulgaris, are capable of forming l(-)-carnitine by hydration of the double bond of crotonobetaine under anaerobic conditions. The carnitine hydrolyase is an inducible cytosolic enzyme which catalyses either the dehydration of l-carnitine or the hydration of crotonobetaine. In growing cultures, the addition of fumarate to a complex or minimal medium stimulated l-carnitine synthesis by diminishing the reduction of crotonobetaine to γ-butyrobetaine. However, l-carnitine synthesis was repressed after addition of nitrate or under aerobic conditions. If the carnitine hydrolyase was induced by l-carnitine or crotonobetaine, these respiratory chain electron acceptors did not impair carnitine formation by resting cells, indicating an epigenetical regulation of carnitine synthesis. Using this bacterial pathway for the biosynthesis of l-carnitine, conditions for producing a high yield are described. The method has some advantages in comparison with other biochemical or microbiological procedures for the production of l-carnitine.

Tài liệu tham khảo

Aurich H, Kleber H-P (1968) Properties of a carnitine transport system in Pseudomonas aeruginosa. Rev Roum Biochim 5:27–37 Bock K, Lundt I, Pedersen C (1983) Synthesis of S- and R-4-amino-3-hydroxy-butyric acid (GABOB) and S- and R-carnitine from arabinose or ascorbic acid. Acta Chem Scand B 37:341–344 Bremer J (1968) Long-chain acyl carnitines. Biochem Prep 12:69–73 Bremer J (1983) Carnitine-metabolism and functions. Physiol Rev 63:1420–1480 Cairney J, Booth IR, Higgins CF (1985) Salmonella typhimurium proP gene encodes a transport system for osmoprotectant betaine. J Bacteriol 164:1218–1223 Cavazza C (1980) Verfahren zur Herstellung des d-Kampferats von l-Carnitinamid und des d-Kampferats von d-Carnitinamid. DE 2, 927, 672 (31. 01. 80) Cavazza C (1982) Verfahren zur enzymatischen Herstellung von l-Carnitin. DE 3, 123, 975 (11. 03. 82) Dropsy EP, Klibanow AM (1984) Cholinesterase-catalyzed resolution of Pugodl-carnitine. Biotechnol Bioeng 26:911–915 Fiorini M, Valentini C (1982) l-Carnitine. EP 60, 595 (22. 09. 82) Fuganti C, Grasselli P (1985) On the steric course of baker's yeast mediated reduction of alkyl 4-azido- and 4-bromo-3-oxobutyrate. Synthesis of (R)- and (S)-carnitine. Tetrahedron Lett 26:101–104 Fuganti C, Grasselli P, Seneci PF, Servi S, Casati P (1986) Immobilized benzylpenicillin acylase: application to the synthesis of optically active forms of carnitine and propranolol. Tetrahedron Lett 27:2061–2062 Jung H, Jung K, Kleber H-P (1987a) Aufnahme von l-Carnitin durch Escherichia coli. 17. Jahrestagung Biochem Ges DDR, Leipzig, E 38, p 19 Jung K, Jung H, Kleber H-P (1987b) Regulation of l-carnitine metabolism in Escherichia coli. J Basic Microbiol 27:131–137 Kanamaru T, Iinuma S, Shinagawa S (1985) l-Carnitine and γ-butyrobetaine production by Emericella. JP 60, 214, 890 (28. 10. 85) Kikuchi H (1986) l-Carnitine and its salts. DE 3, 536, 093 (17. 04. 86) Kleber H-P, Aurich H (1967) Evidence for an inducible active transport of carnitine in Pseudomonas aeruginosa. Biochem Biophys Res Commun 26:255–260 Kulla H, Lehky P (1985) Verfahren zur Herstellung von l-Carnitin auf mikrobiologischem Weg. EP 0, 158, 194 (16. 10. 85) Müller DM, Strack E (1972) Racematspaltung von Pugodl-Carnitin. Hoppe-Seyler's Z Physiol Chem 353:1775–1778 Nakamura U, Takao M, Ueno E, Kawaguchi K (1984) Biochemical method for preparation of optically active carnitine. EP 0, 121, 444 (10. 10. 84) Nakamura T, Ito M, Meno M (1985) Optically active carnitines. JP 60, 214, 898 (28. 10. 85) Nobile S, Deshusses J (1986) Transport of γ-butyrobetaine in an Agrobacterium species isolated from soil. J Bacteriol 168:780–784 Patel SS, Conlon HD, Walt DR (1986) Enzyme-catalyzed synthesis of l-acetylcarnitine and citric acid using acetyl coenzyme A recycling. J Org Chem 51:2842–2844 Pearson DJ, Tubbs PK, Chase JFA (1974) Carnitine and acylcarnitines. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 2nd English edn. Verlag Chemie, Weinheim, pp 1758–1771 Renaud P, Seebach D (1986) Electrochemical decarboxylation of hydroxyproline: a simple three-step conversion of (2 S, 4 R)-4-hydroxyproline to (R)-γ-amino-β-hydroxybutanoic acid (GABOB). Synthesis 5:424–426 Seebach D, Züger MF, Giovannini F, Sonnleitner B, Fiechter A (1984) Präparative mikrobiologische Reduktion von β-Oxoestern mit Thermoanaerobium brockii. Angew Chem 96:155–156 Seim H (1987) Pathobiochemische Grundlagen der Ätiopathogenese von Carnitinmangelsyndromen. Dissertation, Karl-Marx-Universität Leipzig, pp 112–113 Seim H, Ezold R, Kleber H-P, Strack E (1980a) Stoffwechsel des l-Carnitins bei Enterobakterien. Z Allg Mikrobiol 20:591–594 Seim H, Löster H, Strack E (1980b) Kataboler Carnitinstoffwechsel. Reaktionsprodukte der Carnitin-Decarboxylase und der Carnitin-Dehydrogenase in vivo. Hoppe-Seyler's Z Physiol Chem 361:1427–1435 Seim H, Löster H, Claus R, Kleber H-P, Strack E (1982a) Stimulation of the anaerobic growth of Salmonella typhimurium by reduction of l-carnitine, carnitine derivatives and structure—related trimethylammonium compounds. Arch Microbiol 132:91–95 Seim H, Löster H, Claus R, Kleber H-P, Strack E (1982b) Formation of γ-butyrobetaine and trimethylamine from quaternary ammonium compounds stucture related to l-carnitine and choline by Proteus vulgaris. FEMS Microbiol Lett 13:201–205 Seim H, Löster H, Kleber H-P (1982c) Reduktiver Stoffwechsel des l-Carnitins und struckturverwandter Trimethylam-moniumverbindungen in Escherichia coli. Acta Biol Med Germ 41:1009–1018 Seim H, Löster H, Claus R, Kleber H-P, Strack E (1983) Verfahren zur Herstellung von l(-)-Carnitin und seinen Derivaten. DD 221 905 (3. 11. 1983) Seim H, Löster H, Strack E, Kleber H-P (1984) Stereospecific synthesis of l(-)carnitine from crotonobetaine by Escherichia coli. Proc 3rd Eur Congr Biotechnol, Munich, vol I, pp 481–486 Seim H, Jung H, Löster H, Kleber H-P (1985a) Wachstumsstimulation und Stoffwechsel des Carnitins bei Escherichia coli. Wiss Z Karl-Marx-Univ Leipz Math-Naturwiss Reihe 34:287–292 Seim H, Schulze J, Strack E (1985b) Catabolic pathways for high-dosed l(-)- or d(+)-carnitine in germ-free rats? Biol Chem Hoppe-Seyler 366:1017–1021 Sih CJ (1984) Verfahren zur Herstellung von l-Carnitin und Zwischenprodukte für das Verfahren. DE 3, 344, 085 (07. 06. 84) Sih CJ (1985) l-Carnitine. WO 85/04, 900 (07. 11. 85) Strack E, Lorenz I (1960) Process for the preparation of l- and d-carnitine. GB 896, 227 (14. 04. 60) Strack E, Seim H (1979) Die Bildung von γ-Butyrobetain aus exogenum l(-)-Carnitin in vivo bei Maus und Ratte. Hoppe-Seyler's Z Physiol Chem 360:207–215 Tenud L, Gosteli J (1985) Optically active bis (3-chloro-2-hydroxypropyl-trimethylammonium) tartrate. EP 0, 157, 315 (09. 10. 85) Vandecasteele J-P, Lemal J (1980) Enzymatic synthesis of l-carnitine. US 4, 221, 869 (09. 09. 80) Yokozeki K, Kubota K (1984) Method for producing l-carnitine. EP 0, 122, 794 (24. 10. 84) Zhou B, Gopalan AS, Van Middlesworth F, Shieh W-R, Sih CJ (1983) Stereochemical control of yeast reductions. 1. Asymmetric synthesis of l-carnitine. J Am Chem Soc 105:5925–5926