Bacterial biosynthesis of L-DOPA and dopamine

ABSTRACT Master Thesis BACTERIAL BIOSYNTHESIS OF L-DOPA AND DOPAMINE UFUK ÖZER Department of Biology Institute of Natural Sciences Inonu University 57 + x pp. 2006 Supervisor: Hikmet GEÇKİL, Associate Professor L-DOPA, produced by several Gram-negative bacteria, is an important therapeutic agent used for many neurodegenerative diseases, especially Parkinson disease. Another important drug, dopamine, is a catecholamine made from L-DOPA by a single enzymatic step and has therapeutic mode of action in acute circulation disorder and has been applied as a cardio vascular stimulant. Both L-DOPA and dopamine are synthesized either chemically or through the use of bacterial enzymes or bacterial cells themselves. The enzymes for production of L-DOPA and dopamine are regulated with various physical (temperature, oxygen, pH) and chemical (L-tyrosine, monovalent cations) factors. First time in this study L-DOPA, dopamine and tyrosine phenol lyase (TPL), the enzyme catalyzing the conversion of L-DOPA to dopamine, were studied comparatively in several Gram-negative bacteria (Citrobacter freundii, Enterobacter aerogenes, Pseudomonas aeruginosa, Erwinia herbicola) and a Gram-positive bacterium (Streptococcus faecalis) grown under various culture conditions. The highest L-DOPA and dopamine levels in general were observed in relatively early phase (12 h) of cultivation in nutrient rich medium supplemented with L-tirozin. Similarly, TPL activity was also highest in the same cultures. However, all bacteria showed distinct L-DOPA, dopamine and the enzyme profiles under similar culture conditions. The highest and lowest rates were determined for C. freundii and P. aeruginosa, respectively. Noteworthy, E. aerogenes which is not a common strain for production of L-DOPA, had substantially higher levels of this compound than E. herbicola, the most preferred bacterium in this regard. Furthermore, a bacterium (C. freundii and S. faecalis) was determined to produce both L-DOPA and dopamine which were generally been known as compounds synthesized in different bacteria. KEY WORDS: L-DOPA; Dopamine; Catechol; Tyrosine; Tyrosine phenol lyase; Tyrosine decarboxylase; Parkinson disease. m