Biogenesis of novel quinone coenzymes

Abstract

Recently, two novel quinonoid coenzymes, 2,4,5-trihydroxyphenylalanine quinone (topa quinone; TPQ) and tryptophan tryptophylquinone (TTQ), were identified in copper-containing amine oxidase and methylamine dehydrogenase, respectively. Unlike the formerly known quinonoid coenzyme, pyrroloquinoline quinone (PQQ), which is non-covalently bound to several prokaryotic dehydrogenases and produced through its own biosynthetic pathway, each of TPQ and TTQ is bound covalently to the polypeptide chain as an integral amino acid residue and encoded by a codon for a normal (unmodified) amino acid in the gene. Thus, these coenzymes must be generated through post-translational modification of the precursor amino acid; for TPQ, oxidation of a specific tyrosine occurring in the consensus Asn-Tyr-Asp/Glu sequence, and for TTQ, oxidation of a specific tryptophan and cross-linking with another tryptophan separated by 50 residues in the same polypeptide chain. We recently demonstrated that, using the inactive precursor forms of bacterial copper amine oxidases, TPQ is generated through self-processing of the protein with the participation of the bound copper ions. On the other hand, the absence of a prosthetic metal ion in methylamine dehydrogenase as well as its existence in the periplasm renders TTQ biogenesis more complicated, likely requiring an external enzymatic system(s).