Genome organisation and evolution of a eukaryotic nicotinate co-inducible pathway

Bokor, Eszter; Flipphi, Michel; Kocsubé, Sándor; Ámon, Judit; Vágvölgyi, Csaba; Scazzocchio, Claudio; Hamari, Zsuzsanna

doi:10.1101/2021.04.19.440407

Cited by 2 publications

(1 citation statement)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MT707473, MT707472, MN718567, MN718568, MN718569, MN718566, MN718565, KX585439, MT707474, MT707475. The data are provided in electronic supplementary material [60].…”

Section: Data Accessibilitymentioning

confidence: 99%

Genome organization and evolution of a eukaryotic nicotinate co-inducible pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

In Aspergillus nidulans a regulon including 11 hxn genes ( hxnS , T , R , P , Y , Z , X , W , V , M and N ) is inducible by a nicotinate metabolic derivative, repressible by ammonium and under stringent control of the nitrogen-state-sensitive GATA factor AreA and the specific transcription factor HxnR. This is the first report in a eukaryote of the genomic organization of a possibly complete pathway of nicotinate utilization. In A. nidulans the regulon is organized in three distinct clusters, this organization is variable in the Ascomycota . In some Pezizomycotina species all 11 genes map in a single cluster; in others they map in two clusters. This variable organization sheds light on cluster evolution. Instances of gene duplication followed by or simultaneous with integration in the cluster, partial or total cluster loss, and horizontal gene transfer of several genes (including an example of whole cluster re-acquisition in Aspergillus of section Flavi ) were detected, together with the incorporation in some clusters of genes not found in the A. nidulans co-regulated regulon, which underlie both the plasticity and the reticulate character of metabolic cluster evolution. This study provides a comprehensive phylogeny of six members of the cluster across representatives of all Ascomycota classes.

show abstract

“…MT707473, MT707472, MN718567, MN718568, MN718569, MN718566, MN718565, KX585439, MT707474, MT707475. The data are provided in electronic supplementary material [60].…”

Section: Data Accessibilitymentioning

confidence: 99%

Genome organization and evolution of a eukaryotic nicotinate co-inducible pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

Nicotinate degradation in a microbial eukaryote: a novel, complete pathway extant in Aspergillus nidulans

Bokor

Ámon

Varga

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Several strikingly different aerobic and anaerobic pathways of nicotinate utilization had been described in bacteria. No similar work is extant in any eukaryote. Here we elucidate a complete eukaryotic nicotinate utilization pathway, by constructing single or multiple gene deleted strains and identifying metabolic intermediates by ultra-high performance liquid chromatography — high-resolution mass spectrometry. Enzymes catalyzing each step and all intermediate metabolites were identified. We previously established that the cognate eleven genes organized in three clusters constitute a regulon, strictly dependent on HxnR, a pathway-specific transcription factor. The first step, hydroxylation of nicotinic acid to 6-hydroxynicotinic acid is analogous to that occurring in bacterial pathways and is catalyzed by an independently evolved molybdenum-containing hydroxylase. The following enzymatic steps have no prokaryotic equivalents: 6-hydroxynicotinic acid is converted to 2,3,6-trihydroxypyridine through 2,5-dihydroxypiridine and the trihydroxylated pyridine ring is then saturated to 5,6-dihydroxypiperidine-2-one followed by the oxidation of the C6 hydroxyl group resulting in 3-hydroxypiperidine-2,6-dione. The latter two heterocyclic compounds are newly identified cellular metabolites, while 5,6-dihydroxypiperidine-2-one is a completely new chemical compound. Ring opening between C and N results in α-hydroxyglutaramate, an unprecedented compound in prokaryotic nicotinate catabolic routes. The pathway extant in A. nidulans, and in many other ascomycetes, is different from any other previously analyzed in bacteria. Our earlier phylogenetic analysis of Hxn proteins together with the complete novel biochemical pathway we now describe further illustrates the convergent evolution of catabolic pathways between fungi and bacteria.

show abstract

Genome organisation and evolution of a eukaryotic nicotinate co-inducible pathway

Cited by 2 publications

References 58 publications

Genome organization and evolution of a eukaryotic nicotinate co-inducible pathway

Genome organization and evolution of a eukaryotic nicotinate co-inducible pathway

Nicotinate degradation in a microbial eukaryote: a novel, complete pathway extant in Aspergillus nidulans

Contact Info

Product

Resources

About