High performance microbiological transformation of L-tyrosine to L-dopa by Yarrowia lipolytica NRRL-143

Abstract

Background: The 3,4-dihydroxy phenyl L-alanine (L-dopa) is a drug of choice for Parkinson's disease, controlling changes in energy metabolism enzymes of the myocardium following neurogenic injury. Aspergillus oryzae is commonly used for L-dopa production; however, potential improvements in ease of handling, growth rate and environmental impact have led to an interest in exploiting alternative yeasts. The two important elements required for L-dopa production are intracellular tyrosinases (thus pre-grown yeast cells are required for the transformation of Ltyrosine to L-dopa) and L-ascorbate, which acts as a reducing agent.

Innovative use of intact seeds of Mucuna monosperma Wight for improved yield of L-DOPA

“…The L-DOPA was eluted at 0.8 M NaCl. Presence of L-DOPA in the M. monosperma seeds was confirmed as the 1 H NMR and 13 C NMR spectrum Characteristic shifts observed in the 13 C NMR spectrum are shown in Table 2. 13 C NMR spectrum and 1 H NMR spectrum is shown in Fig.…”

“…L-DOPA is a substrate of an enzyme polyphenol oxidase. In its active form, this enzyme transforms L-DOPA to quinones which is having maximum activity at acidic pH 13 . In case of the seed powder, polyphenol oxidase has no activity since cell integrity is lost due to the grinding which was not the case in seeds.…”

“…The fundamental process in enzymatic browning is the transformation of an o-diphenol such as L-DOPA to the corresponding o-quinone, which can undergo further oxidation to brown melanin pigment. 6,13 Ascorbic acid can prevent this enzymatic browning by trapping o-dopaquinone intermediate and converting it into dopahydroquinone which in turn gets converted into L-DOPA. 6 Hence, in the presence of ascorbic acid yield of L-DOPA was improved markedly.…”

Biological sources of L-DOPA: An alternative approach

“…There were many biological soures reported for enantiometrically pure L-DOPA ( Table 1). Stemonitis herbicola 50 mg [25] Aspergillus oryzae ( mutant) 1.28 mg/ml [26] Aspergillus oryzae 1.28 mg/ml [27] Aspergillus oryzae UV7( double mutant) 1.28 mg ml [28] Aspergillus oryzae 1.86 mg/ml [29] Aspergillus oryzae UV-7 444 g cells [30] Aspergillus oryzae ME2 (Illite) 1.686 mg/ml [31] Aspergillus oryzae ME2 (Celite) 0.428 mg/ml [32] Aspergillus oryzae (Double mutant) 300 mg [33] Aspergillus oryzae IIB-6 1.34 mg/ml [34] Acremonium retilum 0.89 mg/ml [35] Aspergillus niger 0.365 mg/ml [36] Actinomycetes 28.6% [37] Yeast Yarrowia lipolytica NRRL-143 2.96 mg/ml [38] Egyptian halophilic black yeast 66 ug/ml [39] Bacteria Vibrio tyrosinaticus 4 mg/ml [40] Pseudomonas melanogenum 8 mg/ml [41] E. coli W(ATCC 11105) (p-hydroxyphenyl acetate 3-hydroxylase) 48 mM in reaction mixture [42] Bacillus sp. JPJ 0.497 mg/ml [7] Recombinant The production of L-DOPA from biological sources involves the oxidation of L-tyrosine by enzyme tyrosinase (E.C.1.14.18.1), which is copper containing enzyme widely distributed in plants, animals and microorganisms [13].…”

“…Similarly, biotransformation of L-DOPA from L-tyrosine was carried out using Acremonium reticulum by submerged fermentation process yields more amount of L-DOPA in the broth [24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Production of L-DOPA also reported from yeast species [38,39].…”