Org Biomol Chem. 2026 Jun 11. doi: 10.1039/d6ob00839a. Online ahead of print.

ABSTRACT

Pyridines are found in many pharmaceuticals and agrochemicals, but are synthesised from fossil fuel conversion. 2,4- and 2,5-pyridinedicarboxylic acids have been reported as products from bioconversion of renewable lignin feedstocks using engineered strains of Rhodococcus jostii RHA1 (Z. Mycroft et al., Green Chem., 2015, 17, 4974-4979), but previously it has been uncertain whether the formation of the pyridine ring was assisted by enzyme catalysis. The 4,5-extradiol ring fission product of protocatechuic acid, 4-carboxy-2-hydroxymuconate 6-semialdehyde (CHMS) shows structural similarity to α-ketoglutaric acid, the substrate for reductive amination by glutamate dehydrogenase (GDH). Testing of five glutamate dehydrogenase (GDH) isozymes from R. jostii RHA1 revealed that GDH5 catalyses NADH-dependent reductive amination of CHMS, and its cyclisation to form a dihydropyridine product. The dihydropyridine can be oxidised to 2,4-pyridinedicarboxylic acid using recombinant P. fluorescens dye-decolorizing peroxidase DyP1B, providing a route to substituted pyridines from a renewable feedstock.

PMID:42300662 | DOI:10.1039/d6ob00839a