Overview on the biotechnological production of L-DOPA

Appl Microbiol Biotechnol. 2015 Jan;99(2):575-84. doi: 10.1007/s00253-014-6215-4. Epub 2014 Nov 30.

Abstract

L-DOPA (3,4-dihydroxyphenyl-L-alanine) has been widely used as a drug for Parkinson's disease caused by deficiency of the neurotransmitter dopamine. Since Monsanto developed the commercial process for L-DOPA synthesis for the first time, most of currently supplied L-DOPA has been produced by the asymmetric method, especially asymmetric hydrogenation. However, the asymmetric synthesis shows critical limitations such as a poor conversion rate and a low enantioselectivity. Accordingly, alternative biotechnological approaches have been researched for overcoming the shortcomings: microbial fermentation using microorganisms with tyrosinase, tyrosine phenol-lyase, or p-hydroxyphenylacetate 3-hydroxylase activity and enzymatic conversion by immobilized tyrosinase. Actually, Ajinomoto Co. Ltd commercialized Erwinia herbicola fermentation to produce L-DOPA from catechol. In addition, the electroenzymatic conversion system was recently introduced as a newly emerging scheme. In this review, we aim to not only overview the biotechnological L-DOPA production methods, but also to briefly compare and analyze their advantages and drawbacks. Furthermore, we suggest the future potential of biotechnological L-DOPA production as an industrial process.

Publication types

  • Review

MeSH terms

  • Biotechnology / methods*
  • Enzymes, Immobilized / metabolism
  • Erwinia / enzymology*
  • Fermentation
  • Levodopa / biosynthesis*
  • Mixed Function Oxygenases / metabolism
  • Monophenol Monooxygenase / metabolism
  • Tyrosine Phenol-Lyase / metabolism

Substances

  • Enzymes, Immobilized
  • Levodopa
  • Mixed Function Oxygenases
  • Monophenol Monooxygenase
  • Tyrosine Phenol-Lyase