Biotransformation of substituted pyridines with dioxygenase-containing microorganisms.
A series of 2-, 3- and 4-substituted pyridines was metabolised using the mutant soil bacterium Pseudomonas putida UV4 which contains a toluene dioxygenase (TDO) enzyme. The regioselectivity of the biotransformation in each case was determined by the position of the substituent. 4-Alkylpyridines were hydroxylated exclusively on the ring to give the corresponding 4-substituted 3-hydroxypyridines, while 3-alkylpyridines were hydroxylated stereoselectively on C-1 of the alkyl group with no evidence of ring hydroxylation. 2-Alkylpyridines gave both ring and side-chain hydroxylation products. Choro- and bromo-substituted pyridines, and pyridine itself, while being poor substrates for P. putida UV4, were converted to some extent to the corresponding 3-hydroxypyridines. These unoptimised biotransformations are rare examples of the direct enzyme-catalysed oxidation of pyridine rings and provide a novel synthetic method for the preparation of substituted pyridinols. Evidence for the involvement of the same TDO enzyme in both ring and side-chain hydroxylation pathways was obtained using a recombinant strain of Escherichia coli (pKST11) containing a cloned gene for TDO. The observed stereoselectivity of the side-chain hydroxylation process in P. putida UV4 was complicated by the action of an alcohol dehydrogenase enzyme in the organism which slowly leads to epimerisation of the initial (R)-alcohol bioproducts by dehydrogenation to the corresponding ketones followed by stereoselective reduction to the (S)-alcohols.
Garrett
Mark D
MD
School of Chemistry and Chemical Engineering, David Keir Building, The Queen's University of Belfast, Belfast, BT9 5AG, UK.
Scott
Robin
R
Sheldrake
Gary N
GN
Dalton
Howard
H
Goode
Paul
P
D001711:Biotransformation; D049308:Dioxygenases / Q000737:chemistry* / Q000378:metabolism; D015394:Molecular Structure; D010084:Oxidation-Reduction; D016958:Pseudomonas putida / Q000201:enzymology*; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism*
D011725:Pyridines; D049308:Dioxygenases