Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes

Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yield...

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Published in:Organic & biomolecular chemistry 2012-01, Vol.10 (4), p.782-790
Main Authors: Boyd, Derek R, Sharma, Narain D, McMurray, Brian, Haughey, Simon A, Allen, Christopher C R, Hamilton, John T G, McRoberts, W Colin, O'Ferrall, Rory A More, Nikodinovic-Runic, Jasmina, Coulombel, Lydie A, O'Connor, Kevin E
Format: Article
Language:English
Subjects:
Crystallography, X-Ray
Dioxygenases - metabolism
Escherichia coli
Escherichia coli - enzymology
Multienzyme Complexes - metabolism
Oxidation-Reduction
Oxygenases - metabolism
Pseudomonas putida - enzymology
Sulfoxides - chemistry
Sulfoxides - metabolism
Thiophenes - chemistry
Thiophenes - metabolism
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Summary:Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[b]thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[b]thiophene sulfoxide and 2-methyl benzo[b]thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b]thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca.: 25-27 kcal mol(-1). The absolute configurations of the benzo[b]thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring.
ISSN:1477-0520
1477-0539
DOI:10.1039/c1ob06678a