Biotechnology Letters

, Volume 36, Issue 11, pp 2193–2198 | Cite as

Biotechnological approach towards a highly efficient production of natural prostaglandins

  • J. C. Guder
  • M. Buchhaupt
  • I. Huth
  • A. Hannappel
  • N. Ferreirós
  • G. Geisslinger
  • J. Schrader
Original Research Paper

Abstract

Prostaglandins (PGs) act as potent local hormones in nearly all tissues of the human body and are used for various medical applications. Heterologous expression of PG endoperoxide H-synthase from the alga, Gracilaria vermiculophylla, into E. coli and the application of this strain in biotransformation experiments resulted in a highly efficient conversion of arachidonic acid (ARA) yielding up to 130 mg natural PGs l−1 in a laboratory scale approach. Detailed analyses of the products and production kinetics were performed, confirming a rapid conversion of ARA to PGs.

Keywords

Arachidonic acid Biotransformation E. coli Gracilaria vermiculophylla Prostaglandin Prostaglandin endoperoxide H-synthase 

References

  1. Andersen NH, Hartzell CJ (1984) High-field 1H NMR studies of prostaglandin H2 and its decomposition pathways. Biochem Biophys Res Commun 120:512–519PubMedCrossRefGoogle Scholar
  2. Bezuglov VV, Serkov IV (2012) Selective protection of hydroxyls in natural type E and F prostaglandins. Chem Nat Compd 48:291–296CrossRefGoogle Scholar
  3. Bundy GL, Schneider WP, Lincoln FH, Pike JE (1972) The synthesis of prostaglandins E 2 and F 2a from (15R)- and (15S)-PGA 2. J Am Chem Soc 94:2123–2124PubMedCrossRefGoogle Scholar
  4. Chen RR (2007) Permeability issues in whole-cell bioprocesses and cellular membrane engineering. Appl Microbiol Biotechnol 74:730–738PubMedCrossRefGoogle Scholar
  5. Coulthard G, Erb W, Aggarwal VK (2012) Stereocontrolled organocatalytic synthesis of prostaglandin PGF2alpha in seven steps. Nature 489:278–281PubMedCrossRefGoogle Scholar
  6. Hamberg M, Svensson J, Wakabayashi T, Samuelsson B (1974) Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Nat Acad Sci USA 71:345–349PubMedCrossRefPubMedCentralGoogle Scholar
  7. Hejkal TW, Camras CB (1999) Prostaglandin analogs in the treatment of glaucoma. Semin Ophthalmol 14:114–123PubMedCrossRefGoogle Scholar
  8. Kaehne F, Buchhaupt M, Schrader J (2011) A recombinant alpha-dioxygenase from rice to produce fatty aldehydes using E. coli. Appl Microbiol Biotechnol 90:989–995PubMedCrossRefGoogle Scholar
  9. Kanamoto H, Takemura M, Ohyama K (2011) Identification of a cyclooxygenase gene from the red alga Gracilaria vermiculophylla and bioconversion of arachidonic acid to PGF(2alpha) in engineered Escherichia coli. Appl Microbiol Biotechnol 91:1121–1129PubMedCrossRefGoogle Scholar
  10. Keirse MJ (2006) Natural prostaglandins for induction of labor and preinduction cervical ripening. Clin Obstet Gynecol 49:609–626PubMedCrossRefGoogle Scholar
  11. Lamačka M, Šajbidor J (1997) Biotechnological production of prostaglandins. Appl Microbiol Biotechnol 47:199–206CrossRefGoogle Scholar
  12. Linke B et al (2012) Analysis of sphingolipid and prostaglandin synthesis during zymosan-induced inflammation. Prostaglandins Other Lipid Mediat 99:15–23PubMedCrossRefGoogle Scholar
  13. Miller SB (2006) Prostaglandins in health and disease: an overview. Semin Arthritis Rheum 36:37–49PubMedCrossRefGoogle Scholar
  14. Simmons DL, Botting RM, Hla T (2004) Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol Rev 56:387–437PubMedCrossRefGoogle Scholar
  15. Summers L (1997) Methods of cervical ripening and labor induction. J Nurse Midwifery 42:71–85PubMedCrossRefGoogle Scholar
  16. Takemura M, Kanamoto H, Nagaya S, Ohyama K (2013) Bioproduction of prostaglandins in a transgenic liverwort, Marchantia polymorpha. Transgenic Res doi:10.1007/s11248-013-9699-2
  17. Varvas K, Kasvandik S, Hansen K, Järving I, Morell I, Samel N (2013) Structural and catalytic insights into the algal prostaglandin H synthase reveal atypical features of the first non-animal cyclooxygenase. Biochim Biophys Acta 1831:863–871PubMedCrossRefGoogle Scholar
  18. Yilmaz E (2001) Biotechnological production of prostaglandin. Biotechnol Adv 19:387–397PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • J. C. Guder
    • 1
  • M. Buchhaupt
    • 1
  • I. Huth
    • 1
  • A. Hannappel
    • 1
  • N. Ferreirós
    • 2
  • G. Geisslinger
    • 2
  • J. Schrader
    • 1
  1. 1.Biochemical EngineeringDECHEMA Research InstituteFrankfurt/MainGermany
  2. 2.Pharmazentrum Frankfurt/ZAFES, Institute of Clinical PharmacologyGoethe-UniversityFrankfurt/MainGermany

Personalised recommendations