type	Journal Article
authors	Yun X, Zhang Q, Lv M, Deng H, Deng Z, Yu Y.
title	In vitro reconstitution of the biosynthetic pathway of 3-hydroxypicolinic acid
journal	Org Biomol Chem
Activity	l-lysine.2-aminotransferase
Family	l-lysine.2-aminotransferase.a
sel	selected
ui	30565646
year	(2019)
volume	17
number	3
pages	454-460
keywords	doi: 10.1039/c8ob02972e
abstract	3-Hydroxypicolinic acid (3-HPA) is an important pyridine building block of bacterial secondary metabolites. Although the main biosynthetic pathways of these metabolites have been identified and well characterized, the enzymatic mechanism underlying the biosynthesis of 3-HPA has yet to be elucidated. In this work, we successfully reconstituted the complete biosynthetic pathway of 3-HPA in vitro. We showed that an l-lysine 2-aminotransferase, a two-component monooxygenase, and a FAD-dependent dehydrogenase are required to convert l-lysine to 3-HPA. We further demonstrated that 3-HPA does not derive from the direct hydroxylation of the picolinic acid at C-3, but from a successive process of C-3 hydroxylation of the piperideine-2-carboxylic acid and tautomerization of the produced 3-hydroxyl dihydropicolinic acid. Therefore, this study unveils the unusual assembly logic of 3-HPA and sheds light on the potential of engineering the 3-HPA pathway for generating novel pyridine-based building blocks.
last changed	2020/02/20 14:45