In Vitro Reconstitution of a Five-Step Pathway for Bacterial Ergothioneine Catabolism

Abstract

The following experimental techniques were used to determine the structure: X-RAY DIFFRACTIONThe reported resolution of this entry is 1.90 Å.Percentile scores (ranging between 0-100) for global validation metrics of the entry are shown in the following graphic. The table shows the number of entries on which the scores are based. MetricWhole archive (#Entries) Similar resolution (#Entries, resolution range(Å)) Clashscore 141614 6847 (1.90-1.90) Ramachandran outliers 138981 6760 (1.90-1.90) Sidechain outliers 138945 6760 (1.90-1.90) Full wwPDB X-ray Structure Validation Report 7NED2 Entry composition i

Matching chemical properties to molecular biological activities opens a new perspective on l‐ergothioneine

“…Although the metabolism of EGT has been investigated for a long time in microorganisms, in terms of its biosynthesis or its decomposition [83,84], very little is known about its catabolism in humans [57]. S-methyl-ergothioneine is the sole known metabolite of EGT in humans and animal that is not derived from its oxidative decomposition.…”

Bacterial Degradation of Nτ-Methylhistidine

“…Conversely, urocanase homologues with different residues at position 455 were predicted to have alternative activities . Indeed, one subfamily was recently identified as TUC (green cluster). , …”

“…As a first catalytic step, the cationic nicotinamide ring forms a carbon–carbon bond with the imidazole ring of the substrate (Figure A) . The related thiourocanate hydratases (TUC) catalyze a similar reaction ( 2c to 3c ) in the degradation of ergothioneine. , Remarkably, these are the only two enzymes known to use NAD + as an electrophilic cofactor, even though NAD + -dependent enzymes are very common in the biosphere.…”

Discovery and structure of a widespread bacterial ABC transporter specific for ergothioneine

“…ET biosynthesis generally begins with Lhistidine, which is trimethylated by a SAM-dependent α-amine methyltransferase into Lhercynine, with the sulfur atom derived from a LMW thiol donor, via the a hercynyl-thiol sulfoxide intermediate. [31][32][33][34] Recent work reveals that ET can also be catabolized by soli-dwelling organisms, as well as by GI tract organisms, likely impacting ET bioavailability in those niches 35 .…”

“…ET biosynthesis generally begins with Lhistidine, which is trimethylated by a SAM-dependent α-amine methyltransferase into Lhercynine, with the sulfur atom derived from a LMW thiol donor, via the a hercynyl-thiol sulfoxide intermediate. [31][32][33][34] Recent work reveals that ET can also be catabolized by soli-dwelling organisms, as well as by GI tract organisms, likely impacting ET bioavailability in those niches 35 .The physiological functions of endogenous ET in various bacterial and fungal organisms have been extensively investigated 36 . In mycobacteria, ET and mycothiol are the two major LMW thiol buffers, and although ET has a much lower cellular abundance relative to mycothiol, it specifically functions in ROS detoxification 37,38 .…”