Crystal Structure of Brucella abortus Deoxyxylulose-5-phosphate Reductoisomerase-like (DRL) Enzyme Involved in Isoprenoid Biosynthesis

Pérez-Gil, Jordi; Calisto, Bárbara M.; Behrendt, Christoph; Kurz, Thomas; Fita, Ignacio; Rodríguez‐Concepción, Manuel

doi:10.1074/jbc.m112.354811

Cited by 9 publications

(16 citation statements)

References 43 publications

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“…Importantly, Roseobacter litoralis , which is known to synthesize carotenoids, codes for a DRL enzyme which was shown to be functional in complementation assays. 62 R. litoralis also codes for a DXR-type enzyme, however, this enzyme is not active in complementation assays. 62 Presumably in the case of R. litoralis carotenoid synthesis relies solely on the activity of DRL for the formation of isoprenoid precursors.…”

Section: Generation Of C5 Isoprenoid Precursorsmentioning

confidence: 99%

“…62 R. litoralis also codes for a DXR-type enzyme, however, this enzyme is not active in complementation assays. 62 Presumably in the case of R. litoralis carotenoid synthesis relies solely on the activity of DRL for the formation of isoprenoid precursors. The, distribution, evolutionary history and role of DRL enzymes is relevant for evaluating the potential of targeting enzymes of the MEP pathway for drug discovery.…”

Section: Generation Of C5 Isoprenoid Precursorsmentioning

confidence: 99%

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Mechanistic Aspects of Carotenoid Biosynthesis

2013

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Section: Generation Of C5 Isoprenoid Precursorsmentioning

confidence: 99%

Section: Generation Of C5 Isoprenoid Precursorsmentioning

confidence: 99%

Mechanistic Aspects of Carotenoid Biosynthesis

2013

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“…DXR-II and DLO sequences showed similarity to NAD(P)-dependent oxidoreductases, and particularly to HD enzymes, at a sequence [ 23 ] and structural level [ 26 ]. Correspondingly, searches for INTERPRO functional domains identified the NAD-binding domain with a core Rossmann-type fold at the N-terminal region of every single protein sequence (domain 1; Figure 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…Examples of enzymes catalyzing identical reactions through the same catalytic mechanisms but showing structurally unrelated active sites are known outside the isoprenoid field [38-41]. In some of these though, key catalytic residues may be conserved between functionally redundant enzymes, as also reported for DXR-I and DXR-II [26]. DXR-I and DXR-II likely represent analogous genes that evolved redundant biochemical functions through mechanistic convergence.…”

Section: Discussionmentioning

confidence: 99%

“…Correspondingly, the recent determination of the DXR-II crystal structure showed only slight structural relationship with DXR-I proteins and revealed a unique arrangement of the active site [26]. Examples of enzymes catalyzing identical reactions through the same catalytic mechanisms but showing structurally unrelated active sites are known outside the isoprenoid field [38-41].…”

Section: Discussionmentioning

confidence: 99%

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Evolutionary diversification and characterization of the eubacterial gene family encoding DXR type II, an alternative isoprenoid biosynthetic enzyme

et al. 2013

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BackgroundIsoprenoids constitute a vast family of natural compounds performing diverse and essential functions in all domains of life. In most eubacteria, isoprenoids are synthesized through the methylerythritol 4-phosphate (MEP) pathway. The production of MEP is usually catalyzed by deoxyxylulose 5-phosphate reductoisomerase (DXR-I) but a few organisms use an alternative DXR-like enzyme (DXR-II).ResultsSearches through 1498 bacterial complete proteomes detected 130 sequences with similarity to DXR-II. Phylogenetic analysis identified three well-resolved clades: the DXR-II family (clustering 53 sequences including eleven experimentally verified as functional enzymes able to produce MEP), and two previously uncharacterized NAD(P)-dependent oxidoreductase families (designated DLO1 and DLO2 for DXR-II-like oxidoreductases 1 and 2). Our analyses identified amino acid changes critical for the acquisition of DXR-II biochemical function through type-I functional divergence, two of them mapping onto key residues for DXR-II activity. DXR-II showed a markedly discontinuous distribution, which was verified at several levels: taxonomic (being predominantly found in Alphaproteobacteria and Firmicutes), metabolic (being mostly found in bacteria with complete functional MEP pathways with or without DXR-I), and phenotypic (as no biological/phenotypic property was found to be preferentially distributed among DXR-II-containing strains, apart from pathogenicity in animals). By performing a thorough comparative sequence analysis of GC content, 3:1 dinucleotide frequencies, codon usage and codon adaptation indexes (CAI) between DXR-II sequences and their corresponding genomes, we examined the role of horizontal gene transfer (HGT), as opposed to an scenario of massive gene loss, in the evolutionary origin and diversification of the DXR-II subfamily in bacteria.ConclusionsOur analyses support a single origin of the DXR-II family through functional divergence, in which constitutes an exceptional model of acquisition and maintenance of redundant gene functions between non-homologous genes as a result of convergent evolution. Subsequently, although old episodic events of HGT could not be excluded, the results supported a prevalent role of gene loss in explaining the distribution of DXR-II in specific pathogenic eubacteria. Our results highlight the importance of the functional characterization of evolutionary shortcuts in isoprenoid biosynthesis for screening specific antibacterial drugs and for regulating the production of isoprenoids of human interest.

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Terpenoid Biosynthesis in Prokaryotes

Boronat

Rodríguez‐Concepción

2014

Advances in Biochemical Engineering/Biotechnology

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Prokaryotic organisms (archaea and eubacteria) are found in all habitats where life exists on our planet. This would not be possible without the astounding biochemical plasticity developed by such organisms. Part of the metabolic diversity of prokaryotes was transferred to eukaryotic cells when endosymbiotic prokaryotes became mitochondria and plastids but also in a large number of horizontal gene transfer episodes. A group of metabolites produced by all free-living organisms is terpenoids (also known as isoprenoids). In prokaryotes, terpenoids play an indispensable role in cell-wall and membrane biosynthesis (bactoprenol, hopanoids), electron transport (ubiquinone, menaquinone), or conversion of light into chemical energy (chlorophylls, bacteriochlorophylls, rhodopsins, carotenoids), among other processes. But despite their remarkable structural and functional diversity, they all derive from the same metabolic precursors. Here we describe the metabolic pathways producing these universal terpenoid units and provide a complete picture of the main terpenoid compounds found in prokaryotic organisms.

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Crystal Structure of Brucella abortus Deoxyxylulose-5-phosphate Reductoisomerase-like (DRL) Enzyme Involved in Isoprenoid Biosynthesis

Cited by 9 publications

References 43 publications

Mechanistic Aspects of Carotenoid Biosynthesis

Mechanistic Aspects of Carotenoid Biosynthesis

Evolutionary diversification and characterization of the eubacterial gene family encoding DXR type II, an alternative isoprenoid biosynthetic enzyme

Terpenoid Biosynthesis in Prokaryotes

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