History Of The Discovery Of PQQ

The first study of PQQ dates back to 1959, while studying glucose metabolism in non-phosphorylated bacteria (which normally metabolize glucose through the glucose-6-phosphate pathway), Acinetobacter calcoaceticus was observed to contain a glucose dehydrogenase (GDH) independent of NAD(P) and FAD. Subsequently, Haug obtained a separable cogroup from this enzyme, whose maximum absorption spectrum was 248nm and the step was 270~ 280nm, and concluded that this cogroup might be a naphthoquinone derivative [1].

Around the same time, scholars became interested in single-celled proteins and biopolysaccharides, and began studying the process by which bacteria metabolize methanol. During this period, several bacteria were found to grow on medium with methanol or methane as the sole carbon source. The key enzyme that bacteria (e.g. Pseudomonas sp M27) metabolizes methanol is methanol dehydrogenase (MDH). In the study of this enzyme, a separable organic cogroup like the glucose dehydrogenase (GDH) was obtained. This cogroup is neither NAD(P) nor FAD.

In the late 1970s, Duine et al. used elctrons pin resonance (ESR), NMR, MS and other technologies to re-study the structure of MDH, and proposed in 1979 that the cogroup of the enzyme was a quinone structure substance containing two N atoms [2]. At the same time, Salisbury et al. analyzed the crystalline acetone adduction of the cogroup by X-ray crystal diffraction technique, and determined that the cogroup was tricarboxypyrrole quinoline quinone structure, whose structural formula was 4, 5-dihydro-4, 5-dioxy-1-hydropyrrole and (2, 3-f) quinolin-2, 7, 9-tricarboxylic acid [3].

The discovery of PQQ was an important event in the history of quinase research. It not only introduced a new cogroup, but also meant the emergence of a new branch of enzymology: quinase, that is, REDOX enzymes with PQQ and other quinones as cogroups. Before the discovery of PQQ, it was thought that there were only two cogroups of NAD/NADP and FAD/FMN in REDOX enzymes.