Escherichia coli QueD Is a 6-Carboxy-5,6,7,8-tetrahydropterin synthase

To elucidate the early steps required during biosynthesis of a broad class of 7-deazapurine-containing natural products, we have studied the reaction catalyzed by Escherichia coli QueD, a 6-pyruvoyl-5,6,7,8-tetrahydropterin synthase (PTPS) homologue possibly involved in queuosine biosynthesis. While mammalian PTPS homologues convert 7,8-dihydroneopterin triphosphate (H ₂NTP) to 6-pyruvoyltetrahydropterin (PPH ₄) in biopterin biosynthesis, E. coli QueD catalyzes the conversion of H ₂NTP to 6-carboxy-5,6,7,8-tetrahydropterin (CPH ₄). E. coli QueD can also convert PPH4 and sepiapterin to CPH ₄, allowing a mechanism to be proposed.