VanA (PP_3736; UniProt Q88GI6) is annotated in UniProt as the vanillate O-demethylase oxygenase subunit with EC 1.14.13.82. The sequence has an N-terminal Rieske [2Fe-2S] domain and a C-terminal VanA_C catalytic domain, consistent with the oxygenase component of a two-component aromatic O-demethylase.
VanA is the oxygenase/Rieske subunit of the two-component VanAB vanillate O-demethylase in KT2440. The 2024 KT2440 O-demethylation engineering paper describes VanAB as the native Rieske non-heme iron monooxygenase and uses vanillate as the model substrate for pathway optimization. PMID:38936762
VanAB-overexpressing KT2440 strains showed faster vanillate utilization, and the same study identifies VanB as the reductase partner for vanillate O-demethylase. This supports vanA as part of the core vanillate catabolic module rather than an incidental side activity. PMID:38936762
VanAB also accepts syringate when overexpressed. A 2021 KT2440 study reports that syringate was O-demethylated to gallate by VanAB and that the specificity of VanAB for syringate was within 25% of that for vanillate. This broadens substrate scope but still points to vanillate O-demethylation as the native, core activity. PMID:33741529 PMID:33741529
Disrupting vanAB blocks downstream vanillic acid metabolism in KT2440. In an engineered strain for vanillic acid production, a vanAB nonfunctional mutant was explicitly selected because it was defective in vanillic acid metabolism. PMID:31809239
KT2440 natively grows on vanillate, and pathway summaries for lignin model compound conversion identify VanAB as the vanillate O-demethylase complex in the upper aromatic pathway. PMID:28299400 PMID:28299400
VanAB abundance is also influenced by catabolite repression. Proteomics in an engineered KT2440 strain identified VanAB as a target of the global Crc regulator, so regulation can modulate flux through vanillate demethylation without changing the underlying catalytic role of VanA. PMID:29188181