HAL will be down for maintenance from Friday, June 10 at 4pm through Monday, June 13 at 9am. More information
Skip to Main content Skip to Navigation
Journal articles

The thiostrepton A tryptophan methyltransferase TsrM catalyses a cob(II)alamin-dependent methyl transfer reaction.

Abstract : Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a novel class of natural products including several antibiotics and bacterial toxins. In countless RiPP biosynthetic pathways, cobalamin-dependent radical SAM (B12/rSAM) enzymes play a pivotal role. In the biosynthetic pathway of the antibiotic and anti-cancer agent thiostrepton A, TsrM, a B12/rSAM enzyme, catalyses the transfer of a methyl group to an electrophilic carbon atom of tryptophan. Here we show that methylcob(III)alamin is the probable physiological enzyme cofactor, and cob(II)alamin rather than cob(I)alamin is a key reaction intermediate. Furthermore, we establish that TsrM and a triple-alanine mutant alkylate cob(II)alamin efficiently leading to the synthesis of MeCbl. Exploiting TsrM substrate ambiguity, we demonstrate that TsrM does not catalyse substrate H-atom abstraction like most radical SAM enzymes. Based on these data, we propose an unprecedented radical-based C-methylation mechanism, which further expands the chemical versatility of rSAM enzymes.
Complete list of metadata

Cited literature [39 references]  Display  Hide  Download

https://hal.univ-grenoble-alpes.fr/hal-01216185
Contributor : Frank Thomas Connect in order to contact the contributor
Submitted on : Wednesday, May 27, 2020 - 9:13:28 AM
Last modification on : Wednesday, April 6, 2022 - 4:08:19 PM

File

2015_Benjdia_Nature Communicat...
Publisher files allowed on an open archive

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

Alhosna Benjdia, Stéphane Pierre, Carmen Gherasim, Alain Guillot, Manon Carmona, et al.. The thiostrepton A tryptophan methyltransferase TsrM catalyses a cob(II)alamin-dependent methyl transfer reaction.. Nature Communications, Nature Publishing Group, 2015, 6, pp.8377. ⟨10.1038/ncomms9377⟩. ⟨hal-01216185⟩

Share

Metrics

Record views

295

Files downloads

16