Monooxygenase- and Dioxygenase-Catalyzed Oxidative Dearomatization of Thiophenes by Sulfoxidation, cis -Dihydroxylation and Epoxidation

Enzymatic oxidations of thiophenes, including thiophene-containing drugs, are important for biodesulfurization of crude oil and drug metabolism of mono- and poly-cyclic thiophenes. Thiophene oxidative dearomatization pathways involve reactive metabolites, whose detection is important in the pharmaceutical industry, and are catalyzed by monooxygenase (sulfoxidation, epoxidation) and dioxygenase (sulfoxidation, dihydroxylation) enzymes. Sulfoxide and epoxide metabolites of thiophene substrates are often unstable, and, while cis-dihydrodiol metabolites are more stable, significant challenges are presented by both types of metabolite. Prediction of the structure, relative and absolute configuration, and enantiopurity of chiral metabolites obtained from thiophene enzymatic oxidation depends on the substrate, type of oxygenase selected, and molecular docking results. The racemization and dimerization of sulfoxides, cis/trans epimerization of dihydrodiol metabolites, and aromatization of epoxides are all factors associated with the mono- and di-oxygenase-catalyzed metabolism of thiophenes and thiophene-containing drugs and their applications in chemoenzymatic synthesis and medicine

Draft Genome Sequences of Pseudomonas putida UV4 and UV4/95, Toluene Dioxygenase-Expressing Producers of cis-1,2-Dihydrodiols

ABSTRACT Here, we present draft genome sequences of Pseudomonas putida strains UV4 and UV4/95, which demonstrate an ability to conduct a wide range of industrially important biotransformations of arenes, alkenes, and phenols. </jats:p

cis‐Dihydroxylation of Tricyclic Arenes and Heteroarenes Catalyzed by Toluene Dioxygenase: A Molecular Docking Study and Experimental Validation

Molecular docking studies of toluene dioxygenase (TDO) led to the prediction that angular and lateral cis‐dihydroxylation of tricyclic arene and heteroarene substrates could occur. Biotransformations of biphenylene, dibenzofuran, carbazole and dibenzothiophene, using P. putida UV4 whole cells expressing TDO, confirmed that both angular and lateral cis‐dihydroxylation occurred in the predicted regioselective and stereoselective manner. The TDO‐catalysed (P. putida UV4) biotransformation of dibenzofuran was optimized, to produce 1,2‐dihydrodibenzofuran‐1,2‐diol as the major metabolite (&gt; 80% yield). 2‐Hydroxydibenzofuran, resulting from dehydration of 1,2‐dihydrodibenzofuran‐1,2‐diol, was also found to undergo cis‐ dihydroxylation to give a very minor cis‐dihydrodiol metabolite (&lt; 2% yield). The enantiopurity (&gt;98% ee) and (1R,2S) absolute configuration of the major dibenzofuran cis ‐dihydrodiol was rigorously established by formation of diMTPA ester derivatives and X‐ray crystallography of a diol epoxide derivative. The cis‐dihydrodiol metabolite of dibenzofuran has potential in the chemoenzymatic synthesis of natural products. dioxygenase‐catalysed cis‐dihydroxylation of substituted phenol and aniline substrates with Pseudomonas putida UV4, yielded arene cis‐dihydrodiol metabolites which tautomerised to the preferred cyclohex‐2‐en‐1‐one cis‐diols, as predicted by molecular docking studies. Further metabolism of cyclohex‐2‐en‐1‐one cis‐diols, under similar conditions, formed 4‐hydroxycyclohex‐2‐en‐1‐ones, as a new type of phenol metabolit