Issue 3, 2019

In vitro reconstitution of the biosynthetic pathway of 3-hydroxypicolinic acid

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.

Graphical abstract: In vitro reconstitution of the biosynthetic pathway of 3-hydroxypicolinic acid

Supplementary files

Article information

Article type
Communication
Submitted
28 Nov. 2018
Accepted
10 Dec. 2018
First published
10 Dec. 2018

Org. Biomol. Chem., 2019,17, 454-460

In vitro reconstitution of the biosynthetic pathway of 3-hydroxypicolinic acid

X. Yun, Q. Zhang, M. Lv, H. Deng, Z. Deng and Y. Yu, Org. Biomol. Chem., 2019, 17, 454 DOI: 10.1039/C8OB02972E

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements