Structure, function, evolution, and application of bacterial Pnu-type vitamin transporters

Abstract

Many bacteria can take up vitamins from the environment via specific transport machineries. Uptake is essential for organisms that lack complete vitamin biosynthesis pathways, but even in the presence of biosynthesis routes uptake is likely preferred, because it is energetically less costly. Pnu transporters represent a class of membrane transporters for a diverse set of B-type vitamins. They were identified 30 years ago and catalyze transport by the mechanism of facilitated diffusion, without direct coupling to ATP hydrolysis or transport of coupling ions. Instead, directionality is achieved by metabolic trapping, in which the vitamin substrate is converted into a derivative that cannot be transported, for instance by phosphorylation. The recent crystal structure of the nicotinamide riboside transporter PnuC has provided the first insights in substrate recognition and selectivity. Here, we will summarize the current knowledge about the function, structure, and evolution of Pnu transporters. Additionally, we will highlight their role for potential biotechnological and pharmaceutical applications.

Underlying mechanisms for syntrophic metabolism of essential enzyme cofactors in microbial communities

“…Two additional one-component transporters, PnuC and PnuT, catalyze transport by facilitated diffusion. Their substrates are phosphorylated by a kinase after uptake, thereby trapping them inside the cell (Jaehme and Slotboom, 2015b). Transport directionality control would, therefore, be impacted by the energy status of the host.…”

Pnu Transporters: Ain’t They SWEET?

“…A comparison based on the crystal structures immediately shows that the GPCR fold is clearly distinct from the Pnu and SWEET folds [root mean square deviation (rmsd) 8 Å and higher], thus refuting the sequence-based predictions. By contrast, the THBs present in the SemiSWEET and PnuC structures have similar structures (rmsd between 1.7 Å and 3.3 Å [9]). The THBs of PnuC are also similar in structure to the THBs in a full-length SWEET, of which the structure was determined recently (rmsd values 2.8 Å).…”

Structural and Functional Characterization of NadR from Lactococcus lactis

“…The substrate specificity of the PnuC protein for NR has been confirmed for homologs from Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Salmonella typhimurium, and Neisseria mucosa [5,6,[10][11][12]. In some organisms, such as Clostridium thermocellum and Nostoc punctiforme, the pnuC gene clusters with nadR [1,2]. NadR converts NR into nicotinamide mononucleotide (NMN) and subsequently into NAD [13].…”

“…Nicotinamide riboside (NR, a form of Vitamin B3) is one of the common precursors for biosynthesis of nicotinamide adenine dinucleotide (NAD) [1,2]. In some prokaryotes, NR is taken up by PnuC membrane transporters via a facilitated-diffusion transport mechanism [3][4][5][6][7][8].…”