The Ferric-superoxo Intermediate of the TxtE Nitration Pathway Resists Reduction, Facilitating Its Reaction with Nitric Oxide

22 June 2021, Version 2
This content is a preprint and has not undergone peer review at the time of posting.


TxtE is a cytochrome P450 (CYP) homolog that mediates the nitric oxide (NO)-dependent direct nitration of L-tryptophan (Trp) to form 4-nitro-L-tryptophan (4-NO2-Trp). A recent report showed evidence that TxtE activity requires NO to react with a ferric-superoxo intermediate. Given this minimal mechanism, it is not clear how TxtE avoids Trp hydroxylation, a mechanism that also traverses the ferric-superoxo intermediate. Our combined results suggest 1) autoxidation is the sole TxtE uncoupling pathway and 2) the TxtE ferric-superoxo intermediate cannot be reduced by these electron transfer partners. We conclude that resistance of the ferric-superoxo intermediate to reduction is a key feature of TxtE that increases the lifetime of the intermediate and enables its reaction with NO and efficient nitration activity.


Nitric oxide
natural product
nitration mixture

Supplementary materials

Supplementary figures for "The ferric-superoxo intermediate of the TxtE nitration pathway resists reduction, facilitating its reaction with nitric oxide"
Supplementary figures and data


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