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

Xuan Yun, Qian Zhang, Meinan Lv, Hai Deng, Zixin Deng, Yi Yu

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)454-460
Number of pages7
JournalOrganic & Biomolecular Chemistry
Volume17
Issue number3
Early online date10 Dec 2018
DOIs
Publication statusPublished - 21 Jan 2019

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Biosynthetic Pathways
acids
Hydroxylation
Metabolites
dimethylaniline monooxygenase (N-oxide forming)
metabolites
lysine
pyridines
Flavin-Adenine Dinucleotide
Biosynthesis
Carboxylic Acids
Mixed Function Oxygenases
3-hydroxypicolinic acid
In Vitro Techniques
Hydroxyl Radical
biosynthesis
dehydrogenases
Lysine
Oxidoreductases
carboxylic acids

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In vitro reconstitution of the biosynthetic pathway of 3-hydroxypicolinic acid. / Yun, Xuan; Zhang, Qian; Lv, Meinan; Deng, Hai; Deng, Zixin; Yu, Yi.

In: Organic & Biomolecular Chemistry, Vol. 17, No. 3, 21.01.2019, p. 454-460.

Research output: Contribution to journalArticle

Yun, Xuan ; Zhang, Qian ; Lv, Meinan ; Deng, Hai ; Deng, Zixin ; Yu, Yi. / In vitro reconstitution of the biosynthetic pathway of 3-hydroxypicolinic acid. In: Organic & Biomolecular Chemistry. 2019 ; Vol. 17, No. 3. pp. 454-460.
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N2 - 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.

AB - 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.

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