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. 2016 May 25;138(20):6424-6.
doi: 10.1021/jacs.6b00583. Epub 2016 May 10.

Dibenzothiophene Catabolism Proceeds via a Flavin-N5-oxide Intermediate

Sanjoy Adak  1 , Tadhg P Begley  1
Affiliations

Dibenzothiophene Catabolism Proceeds via a Flavin-N5-oxide Intermediate

Sanjoy Adak et al. J Am Chem Soc. .

Abstract

The dibenzothiophene catabolic pathway converts dibenzothiophene to 2-hydroxybiphenyl and sulfite. The third step of the pathway, involving the conversion of dibenzothiophene sulfone to 2-(2-hydroxyphenyl)-benzenesulfinic acid, is catalyzed by a unique flavoenzyme DszA. Mechanistic studies on this reaction suggest that the C2 hydroperoxide of dibenzothiophene sulfone reacts with flavin to form a flavin-N5-oxide. The intermediacy of the flavin-N5-oxide was confirmed by LC-MS analysis, a co-elution experiment with chemically synthesized FMN-N5-oxide and (18)O2 labeling studies.

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Figures

Figure 1.
Figure 1.
Four-step dibenzothiophene catabolic pathway in Rhodococcus erythropolis.
Figure 2.
Figure 2.
SRN1 mechanistic proposal for the DszA-catalyzed reaction.
Figure 3.
Figure 3.
LC-MS analysis of the DszA reaction run in [18O]-H2O/16O2 buffer or H2O/18O2. Panel A shows that oxygen from the buffer is not incorporated into the reaction product 4. Panel B shows the incorporation of a single oxygen atom from molecular oxygen; m/z for 4 and [18O1]-4 are 235 and 237 Da, respectively.
Figure 4.
Figure 4.
Proposed DszA-catalyzed dibenzothiophene sulfone ring opening via a flavin hydroperoxide intermediate.
Figure 5.
Figure 5.
Characterization of a new intermediate in the DszA-catalyzed reaction. (A) Partial HPLC chromatogram of the DszA/photoreduced FMN reaction mixture showing the new intermediate (I20.3) eluting at 20.3 min. The peak eluting at 20.1 min corresponds to an impurity present in commercial FMN. (B) Co-elution of I20.3 with synthesized FMN-N5-oxide. (C) UV−vis spectra of FMN and FMN-N5-oxide. The I20.3 spectrum was identical to that of FMN-N5-oxide. (D) Extracted ion chromatograms for [M + H] = 473.1 Da demonstrate that I20.3 is present only in the full reaction mixture. (E) Exact mass of I20.3 consistent with the mass expected for FMN-N5-oxide ([M + H] = 473.11 Da). (F) Exact mass of I20.3 generated using 18O2 consistent with the mass expected for [18O1]-FMN-N5-oxide ([M + H] = 475.11 Da).
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