Fine-tuning of a radical-based reaction by radical S-adenosyl-L-methionine tryptophan lyase

• Autores: Giuseppe Sicoli, Jean-Marie Mouesca, Laura Zeppieri, Patricia Amara
• Localización: Science, ISSN 0036-8075, Vol. 351, Nº 6279, 2016, págs. 1320-1323
• Idioma: inglés
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• Resumen

  • The radical S-adenosyl-L-methionine tryptophan lyase NosL converts L-tryptophan into 3-methylindolic acid, which is a precursor in the synthesis of the thiopeptide antibiotic nosiheptide. Using electron paramagnetic resonance spectroscopy and multiple L-tryptophan isotopologues, we trapped and characterized radical intermediates that indicate a carboxyl fragment migration mechanism for NosL. This is in contrast to a proposed fragmentation-recombination mechanism that implied Cα–Cβ bond cleavage of L-tryptophan. Although NosL resembles related tyrosine lyases, subtle substrate motions in its active site are responsible for a fine-tuned radical chemistry, which selects the Cα–C bond for disruption. This mechanism highlights evolutionary adaptation to structural constraints in proteins as a route to alternative enzyme function.