Isolation of a 2-picolinic acid-assimilating bacterium and its proposed degradation pathway

Zhao

et al. 2019

J Bacteriol

Picolinic acid (PA) is a natural toxic pyridine derivative. Microorganisms can degrade and utilize PA for growth. However, the full catabolic pathway of PA and its physiological and genetic foundation remain unknown. In this study, we identified a gene cluster, designated picRCEDFB4B3B2B1A1A2A3, responsible for the degradation of PA from Alcaligenes faecalis JQ135. Our results suggest that PA degradation pathway occurs as follows: PA was initially 6-hydroxylated to 6-hydroxypicolinic acid (6HPA) by PicA (a PA dehydrogenase). 6HPA was then 3-hydroxylated by PicB, a four-component 6HPA monooxygenase, to form 3,6-dihydroxypicolinic acid (3,6DHPA), which was then converted into 2,5-dihydroxypyridine (2,5DHP) by the decarboxylase PicC. 2,5DHP was further degraded to fumaric acid through PicD (2,5DHP 5,6-dioxygenase), PicE (N-formylmaleamic acid deformylase), PicF (maleamic acid amidohydrolase), and PicG (maleic acid isomerase). Homologous pic gene clusters with diverse organizations were found to be widely distributed in Alpha-, Beta-, and Gammaproteobacteria. Our findings provide new insights into the microbial catabolism of environmental toxic pyridine derivatives. IMPORTANCE Picolinic acid is a common metabolite of L-tryptophan and some aromatic compounds and is an important intermediate in organic chemical synthesis. Although the microbial degradation/detoxification of picolinic acid has been studied for over 50 years, the underlying molecular mechanisms are still unknown. Here, we show that the pic gene cluster is responsible for the complete degradation of picolinic acid. The pic gene cluster was found to be widespread in other Alpha-, Beta-, and Gammaproteobacteria. These findings provide a new perspective for understanding the catabolic mechanisms of picolinic acid in bacteria.

mentioning

confidence: 99%

Identification and Characterization of a Novel pic Gene Cluster Responsible for Picolinic Acid Degradation in Alcaligenes faecalis JQ135

Zhao

et al. 2019

J Bacteriol

“…Z2 (33), and the UGN strain (34). Further, another intermediate compound, 2,5DHP has been detected in the media during PA degradation in few strains (32, 34). However, the intermediate 3,6DHPA, a key link between 6HPA and 2,5DHP, was hardly detectable.…”

Section: Discussionmentioning

confidence: 99%

“…(28), Alcaligenes faecalis DSM 6269 (29), Arthrobacter picolinophilus DSM 20665 (30, 39), Burkholderia sp. ZD1 (32), Streptomyces sp. Z2 (33), and the UGN strain (34).…”

Section: Discussionmentioning

confidence: 99%

“…However, PA can be degraded by microorganisms in the natural environment (15). Numerous PA-degrading bacterial strains have been isolated including Achromobacter (27), Aerococcus (28), Alcaligenes (29), Arthrobacter (30), Bacillus (31), Burkholderia (32), or Streptomyces (33). The metabolic pathway of PA in microorganisms has been partially elucidated in previous studies (15, 28, 32) (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Novel 3,6-Dihydroxypicolinic Acid Decarboxylase Mediated Picolinic Acid Catabolism inAlcaligenes faecalisJQ135

Zhang

Yao

et al. 2018

Preprint

22Alcaligenes faecalis strain JQ135 utilizes picolinic acid (PA) as sole carbon and 23 nitrogen source for growth. In this study, we screened a 6-hydroxypicolinic acid 24 (6HPA) degradation-deficient mutant through random transposon mutagenesis. The 25 mutant hydroxylated 6HPA into an intermediate, identified as 3,6-dihydroxypicolinic 26 acid (3,6DHPA) with no further degradation. A novel decarboxylase PicC was 27 identified that was found to be responsible for the decarboxylation of 3,6DHPA to 28 2,5-dihydroxypyridine. Although, PicC belonged to amidohydrolase_2 family, it 29 shows low similarity (<45%) when compared to other reported amidohydrolase_2 30 family decarboxylases. Moreover, PicC was found to form a monophyletic group in 31 the phylogenetic tree constructed using PicC and related proteins. Further, the genetic 32 deletion and complementation results demonstrated that picC was essential for PA 33 degradation. The PicC was Zn 2+ -dependent non-oxidative decarboxylase that can 34 specifically catalyze the irreversible decarboxylation of 3,6DHPA to 35 2,5-dihydroxypyridine. The K m and k cat towards 3,6DHPA were observed to be 13.44 36 μM and 4.77 s -1 , respectively. Site-directed mutagenesis showed that His163 and 37 His216 were essential for PicC activity. 38 39 40 3 / 25

“…No reports showed that PA could be metabolized by humans (18). Nevertheless, numerous microorganisms were found to degrade PA, such as Alcaligenes (19), Arthrobacter (20), Burkholderia (21), Streptomyces (22), and an unidentified Gram-negative bacterium (designated as UGN strain) (23). The bacterial degradation pathway of PA was proposed as: PA, 6-hydroxypicolinic acid (6HPA),3,6-dihydroxypicolinic acid (3,6DHPA), and 2,5-dihydroxypyridine (2,5DHP), according to several previous determinations of degradation intermediates and crude enzymes (Fig.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of a novelpicgene cluster responsible for picolinic acid degradation inAlcaligenes faecalisJQ135

Zhao

et al. 2019

Preprint

20Picolinic acid (PA) is a natural toxic pyridine derivative. Microorganisms can 21 degrade and utilize PA for growth. However, the full metabolic pathway and its 22 physiological and genetic foundation remain unknown. In this study, we identified the 23 pic gene cluster responsible for the complete degradation of PA from Alcaligenes 24 faecalis JQ135. PA was initially 6-hydroxylated into 6-hydroxypicolinic acid (6HPA) 25 by PA dehydrogenase (PicA). 6HPA was then 3-hydroxylated by a four-component 26 6HPA monooxygenase (PicB) to form 3,6-dihydroxypicolinic acid (3,6DHPA), which 27 was then converted into 2,5-dihydroxypyridine (2,5DHP) by a decarboxylase (PicC). 28 The 2,5DHP was further degraded into fumaric acid, through PicD (2,5DHP 29 dioxygenase), PicE (N-formylmaleamic acid deformylase), PicF (maleamic acid 30 amidohydrolase), and PicG (maleic acid isomerase). Homologous pic gene clusters 31 with diverse organizations were found to be widely distributed in α-, β-, and 32 γ-Proteobacteria. Our findings provide new insights into the microbial metabolism of 33 environmental toxic pyridine derivatives. 34 35 36 3 / 20 Importance 37 Picolinic acid is a common metabolite of L-tryptophan and some aromatic 38 compounds and is an important intermediate of industrial concern. Although the 39 microbial degradation/detoxification of picolinic acid has been studied for over 50 40 years, the underlying molecular mechanisms are still unknown. Here, we show the pic 41 gene cluster responsible for the complete degradation of picolinic acid into the 42 tricarboxylic acid cycle. This gene cluster was found to be widespread in other α-, β-, 43 and γ-Proteobacteria. These findings provide new perspective for understanding the 44 mechanisms of picolinic acid biodegradation in bacteria. 45 46 4 / 20 157 PicF showed high similarities (40~60%) to 2,5DHP 5,6-dioxygenase, NFM 158