A Study on the Electrochemical Synthesis of L-DOPA Using Oxidoreductase Enzymes: Optimization of an Electrochemical Process

Rahman, Siti Fauziyah; Gobikrishnan, Sriramulu; Indrawan, Natarianto; Park, Seok-Hwan; Park, Jae-Hee; Min, Kyoungseon; Yoo, Young Je; Park, Don-Hee

doi:10.4014/jmb.1206.06043

Cited by 6 publications

(10 citation statements)

References 17 publications

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“…Even immobilization of the enzyme is not sufficient to reach considerably higher conversion, although increased stability can be observed in these processing conditions. The final result was that an average substrate conversion of 31–34% was obtained for aerated mixtures containing both enzyme preparations (other authors: 1.9–53%; [ 19 , 20 , 23 , 24 , 29 , 33 ]). Thus, efforts to decrease the effective concentrations of both reactants in the vicinity of the enzyme are necessary.…”

Section: Resultsmentioning

confidence: 97%

“…However, the excess AH 2 is unfavorable because ascorbic acid is recognized by tyrosinase as (i) a diphenolic substrate (ascorbate oxidase) [ 31 ] and (ii) a strong inactivator of the enzyme [ 32 ]. These phenomena and low tyrosinase stability are believed responsible for the low reaction yields (1.9–53% L-DOPA) [ 19 , 20 , 23 , 24 , 29 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the low residence time resulted in a low reaction yield (up to 10%). To avoid the problem of AH 2 supplementation, electroenzymatic systems [ 21 , 33 , 38 ] with native tyrosinase or tyrosinase that was immobilized on a cathode were proposed and yielded 40–96% conversion, depending on the form of the enzyme, but with a strong limitation on the cathode size. An interesting approach to reduce diphenolics accumulation and inactivation by AH 2 was presented by Marin-Zamora et al [ 28 ], which is based on the known complexation of o -diphenols with borate ions [ 39 ].…”

Section: Introductionmentioning

confidence: 99%

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Effective L-Tyrosine Hydroxylation by Native and Immobilized Tyrosinase

et al. 2016

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Hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (L-DOPA) by immobilized tyrosinase in the presence of ascorbic acid (AH2), which reduces DOPA-quinone to L-DOPA, is characterized by low reaction yields that are mainly caused by the suicide inactivation of tyrosinase by L-DOPA and AH2. The main aim of this work was to compare processes with native and immobilized tyrosinase to identify the conditions that limit suicide inactivation and produce substrate conversions to L-DOPA of above 50% using HPLC analysis. It was shown that immobilized tyrosinase does not suffer from partitioning and diffusion effects, allowing a direct comparison of the reactions performed with both forms of the enzyme. In typical processes, additional aeration was applied and boron ions to produce the L-DOPA and AH2 complex and hydroxylamine to close the cycle of enzyme active center transformations. It was shown that the commonly used pH 9 buffer increased enzyme stability, with concomitant reduced reactivity of 76%, and that under these conditions, the maximal substrate conversion was approximately 25 (native) to 30% (immobilized enzyme). To increase reaction yield, the pH of the reaction mixture was reduced to 8 and 7, producing L-DOPA yields of approximately 95% (native enzyme) and 70% (immobilized). A three-fold increase in the bound enzyme load achieved 95% conversion in two successive runs, but in the third one, tyrosinase lost its activity due to strong suicide inactivation caused by L-DOPA processing. In this case, the cost of the immobilized enzyme preparation is not overcome by its reuse over time, and native tyrosinase may be more economically feasible for a single use in L-DOPA production. The practical importance of the obtained results is that highly efficient hydroxylation of monophenols by tyrosinase can be obtained by selecting the proper reaction pH and is a compromise between complexation and enzyme reactivity.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effective L-Tyrosine Hydroxylation by Native and Immobilized Tyrosinase

et al. 2016

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“…The sample treated in this manner was shaken briefly in a vortex mixer. Since formation of L-DOPA complex is time dependent, substantial L-DOPA concentration was determined after one hour spectroscopically at 414 nm [15,16].…”

Section: -2-3 Quantitative Analysismentioning

confidence: 99%

“…This might be the cause for the difference in cathode and anode potential for the electrochemical reaction. Rahman et al [16] conducted the optimization of an electrochemical L-DOPA synthesis and reported that L-DOPA has and oxidation peak at 376 mV and a reduction peak at −550 mV. This peak difference also might be from different working electrode material.…”

Section: -2 Cyclic Voltammogram Of L-dopamentioning

confidence: 99%

L-DOPA Synthesis Using Tyrosinase-immobilized on Electrode Surfaces

Rahman

Gobikhrisnan

Gozan

et al. 2016

Korean Chemical Engineering Research

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− Levodopa or L-3,4-dihydroxyphenylalanine (L-DOPA) is the direct precursor of the neurotransmitter dopamine. L-DOPA is a well-known neuroprotective agent for the treatment of Parkinson's disease symptoms. L-DOPA was synthesized using the enzyme, tyrosinase, as a biocatalyst for the conversion of L-tyrosine to L-DOPA and an electrochemical method for reducing L-DOPAquinone, the product resulting from enzymatic synthesis, to L-DOPA. In this study, three electrode systems were used: A glassy carbon electrode (GCE) as working electrode, a platinum, and a Ag/ AgCl electrode as auxiliary and reference electrodes, respectively. GCE has been modified using electropolymerization of pyrrole to facilitate the electron transfer process and immobilize tyrosinase. Optimum conditions for the electropolymerization modified electrode were a temperature of 30 o C and a pH of 7 producing L-DOPA concentration 0.315 mM. After 40 days, the relative activity of an enzyme for electropolymerization remained 38.6%, respectively.

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Overview on the biotechnological production of l-DOPA

Min

Park

et al. 2014

Appl Microbiol Biotechnol

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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.

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A Study on the Electrochemical Synthesis of L-DOPA Using Oxidoreductase Enzymes: Optimization of an Electrochemical Process

Cited by 6 publications

References 17 publications

Effective L-Tyrosine Hydroxylation by Native and Immobilized Tyrosinase

Effective L-Tyrosine Hydroxylation by Native and Immobilized Tyrosinase

L-DOPA Synthesis Using Tyrosinase-immobilized on Electrode Surfaces

Overview on the biotechnological production of l-DOPA

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