Abstract
L-DOPA (3,4-dihydroxyphenyl-L-alanine), a modified amino acid, is an expansively used drug for the Parkinson’s disease treatment. In the present study, optimization of nutritional parameters influencing L-DOPA production was attempted using the response surface methodology (RSM) from Mucuna monosperma callus. Optimization of the four factors was carried out using the Box–Behnken design. The optimized levels of factors predicted by the model include tyrosine 0.894 g l-1, pH 4.99, ascorbic acid 31.62 mg l-1and copper sulphate 23.92 mg l-1, which resulted in highest L-DOPA yield of 0.309 g l-1. The optimization of medium using RSM resulted in a 3.45-fold increase in the yield of L-DOPA. The ANOVA analysis showed a significant R2 value (0.9912), model F-value (112.465) and probability (0.0001), with insignificant lack of fit. Optimized medium was used in the laboratory scale column reactor for continuous production of L-DOPA. Uninterrupted flow column exhibited maximum L-DOPA production rate of 200 mg L-1 h-1 which is one of the highest values ever reported using plant as a biotransformation source. L-DOPA production was confirmed by HPTLC and HPLC analysis. This study demonstrates the synthesis of L- DOPA using Mucuna monosperma callus using a laboratory scale column reactor.
Highlights
Parkinson’s disease (PD) is a progressive disorder of the nervous system primarily affecting the motor system of the body and is known as “Shaking palsy”
The most effective therapy for PD is administration of a modified amino acid known as L-DOPA (3-(3, 4-dihydroxyphenyl)-Lalanine), which is converted to dopamine in the brain
Less or no efforts were attempted towards development of a cost effective process for L-DOPA production using plant sources by biotransformation approach
Summary
Parkinson’s disease (PD) is a progressive disorder of the nervous system primarily affecting the motor system of the body and is known as “Shaking palsy”. The most effective therapy for PD is administration of a modified amino acid known as L-DOPA (3-(3, 4-dihydroxyphenyl)-Lalanine), which is converted to dopamine in the brain. L-DOPA, a dopamine precursor, either alone or in combination with an aromatic amino acid decarboxylase inhibitor (carbidopa, benserazide) is the most effective drug for the treatment of PD, since dopamine fails to pass through the blood brain barrier (Kofman 1971). The natural source consisting of seeds of M. pruriens and allied species are widely used for medication since chemical synthesis of this drug is costly and hindered with disadvantage of racemic mixture which inhibits the dopa decaboxylase activity in human body (Krishnaveni et al 2009)
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