Kinetic modeling and statistical optimization of submerged production of anti-Parkinson's prodrug L-DOPA by Pseudomonas fluorescens

Prep Biochem Biotechnol. 2022;52(3):331-343. doi: 10.1080/10826068.2021.1945624. Epub 2021 Jul 20.

Abstract

L-DOPA, a precursor of dopamine, is the drug of choice for Parkinson's disease, which persists due to decreased levels of dopamine in the brain. Present study emphasis the microbial production of L-DOPA rather than the biotransformation of L-DOPA by L-tyrosine. The production of L-DOPA by bacterial isolates had gained more acceptance due to its more straightforward extraction and downstream processes. Pseudomonas fluorescens was used to produce the L-DOPA in a bioreactor system under submerged condition. The design of experiment-based Taguchi orthogonal array method was adopted for the optimization of production. L-9 orthogonal array using the analysis of mean approach was used to study the effect of different factors viz NaCl, lactose, tryptone, and inducer on the microbial production of L-DOPA. The method mentioned above is less time consuming and does not require any harsh chemicals, proving it to be an eco-friendly process. After optimizing selected factors, i.e., NaCl (1.2 g/l), lactose (1.5 g/l), tryptone (4 g/l), and inducer (0.1 g/l), 16.9 % of enhancement in L-DOPA production with 66.6% of process cost saving was observed. The production of L-DOPA was increased from 3.426 ± 0.08 g/l to 4.123 ± 0.05 g/l after optimization. Subsequently, unstructured kinetic models were adopted to simulate the fermentation kinetics and understand the metabolic process. Fisher' F test and determination coefficients (R2) confirmed that the Velhurst-Pearl logistic equation, Luedeking-Piret equation, and modified Luedeking-Piret equation was best fitted with the biomass production, product formation, and substrate utilization, respectively.

Keywords: Dopamine; L-DOPA; Pseudomonas fluorescens; Taguchi; orthogonal array; unstructured kinetics.

MeSH terms

  • Antiparkinson Agents / metabolism*
  • Biotransformation
  • Kinetics
  • Lactose / chemistry
  • Levodopa / metabolism*
  • Models, Biological*
  • Prodrugs / metabolism*
  • Pseudomonas fluorescens / metabolism*
  • Sodium Chloride / chemistry
  • Tyrosine / metabolism

Substances

  • Antiparkinson Agents
  • Prodrugs
  • Tyrosine
  • Sodium Chloride
  • Levodopa
  • Lactose