Made by the barrel load: The biosynthetic pathway of the recently discovered 22nd amino acid, pyrrolysine, starts with an isomerization of lysine to methylornithine, catalyzed by PylB. The X-ray crystal structure of PylB is determined (see picture) and shows it has a TIM barrel fold. The sealed central cavity contains a [4Fe-4S] cluster, S-adenosylmethionine (SAM), and methylornithine, whose 2R,3R configuration could be confirmed. The data suggest a fragmentation-recombination mechanism via a glycyl radical intermediate. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.