Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Structural View on the Stereospecificity of Plant Borneol-Type Dehydrogenases.

ABSTRACT: The development of sustainable processes for the valorization of byproducts and other waste streams remains an ongoing challenge in the field of catalysis. Racemic borneol, isoborneol and camphor are currently produced from α-pinene, a side product from the production of cellulose. The pure enantiomers of these monoterpenoids have numerous applications in cosmetics and act as reagents for asymmetric synthesis, making an enzymatic route for their separation into optically pure enantiomers a desirable goal. Known short-chain borneol-type dehydrogenases (BDHs) from plants and bacteria lack the required specificity, stability or activity for industrial utilization. Prompted by reports on the presence of pure (-)-borneol and (-)-camphor in essential oils from rosemary, we set out to investigate dehydrogenases from the genus Salvia and discovered a dehydrogenase with high specificity (E>120) and high specific activity (>0.02 U mg^-1) for borneol and isoborneol. Compared to other specific dehydrogenases, the one reported here shows remarkably higher stability, which was exploited to obtain the first three-dimensional structure of an enantiospecific borneol-type short-chain dehydrogenase. This, together with docking studies, led to the identification of a hydrophobic pocket in the enzyme that plays a crucial role in the stereo discrimination of bornane-type monoterpenoids. The kinetic resolution of borneol and isoborneol can be easily integrated into the existing synthetic route from α-pinene to camphor thereby allowing the facile synthesis of optically pure monoterpenols from an abundant renewable source.

SUBMITTER: Chanique AM

PROVIDER: S-EPMC8261865 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Structural characterization of borneol dehydrogenase from Pseudomonas sp. TCU-HL1.

Project description:During the microbial degradation of borneol, a bicyclic plant monoterpene, it is first converted into camphor by borneol dehydrogenase (BDH) and then enters a known camphor-degradation pathway. Previously, a recombinant Pseudomonas BDH was found in inclusion bodies when expressed in Escherichia coli. After refolding, it was still unstable and was difficult to concentrate. Here, the protein-expression conditions were improved by changing the medium from lysogeny broth to Terrific Broth, yielding a soluble form of the enzyme with higher activity. The protein was crystallized and its 3D structure was determined by X-ray diffraction. Like other known homologues such as quinuclidinone reductase, the protein forms a tetramer with subunits containing Rossmann folds. Structural comparison revealed major differences in the C-terminal helices and the associated loops. It is likely that these regions contain the determinants for substrate recognition.

| S-EPMC7336358 | biostudies-literature

An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases.

Project description:Malate and lactate dehydrogenases (MDH and LDH) are homologous, core metabolic enzymes that share a fold and catalytic mechanism yet possess strict specificity for their substrates. In the Apicomplexa, convergent evolution of an unusual LDH from MDH produced a difference in specificity exceeding 12 orders of magnitude. The mechanisms responsible for this extraordinary functional shift are currently unknown. Using ancestral protein resurrection, we find that specificity evolved in apicomplexan LDHs by classic neofunctionalization characterized by long-range epistasis, a promiscuous intermediate, and few gain-of-function mutations of large effect. In canonical MDHs and LDHs, a single residue in the active-site loop governs substrate specificity: Arg102 in MDHs and Gln102 in LDHs. During the evolution of the apicomplexan LDH, however, specificity switched via an insertion that shifted the position and identity of this 'specificity residue' to Trp107f. Residues far from the active site also determine specificity, as shown by the crystal structures of three ancestral proteins bracketing the key duplication event. This work provides an unprecedented atomic-resolution view of evolutionary trajectories creating a nascent enzymatic function.

| S-EPMC4109310 | biostudies-literature

The dual targeting ability of type II NAD(P)H dehydrogenases arose early in land plant evolution.

Project description:BackgroundType II NAD(PH) dehydrogenases are located on the inner mitochondrial membrane of plants, fungi, protists and some primitive animals. However, recent observations have been made which identify several Arabidopsis type II dehydrogenases as dual targeted proteins. Targeting either mitochondria and peroxisomes or mitochondria and chloroplasts.ResultsMembers of the ND protein family were identified in various plant species. Phylogenetic analyses and subcellular targeting predictions were carried out for all proteins. All ND proteins from three model plant species Arabidopsis, rice and Physcomitrella were cloned as N- and C-terminal GFP fusions and subcellular localisations were determined. Dual targeting of plant type II dehydrogenases was observed to have evolved early in plant evolution and to be widespread throughout different plant species. In all three species tested dual targeting to both mitochondria and peroxisomes was found for at least one NDA and NDB type protein. In addition two NDB type proteins from Physcomitrella were also found to target chloroplasts. The dual targeting of NDC type proteins was found to have evolved later in plant evolution.ConclusionsThe functions of type II dehydrogenases within plant cells will have to be re-evaluated in light of this newly identified subcellular targeting information.

| S-EPMC3716789 | biostudies-literature

Mapping key amino acid residues for the epimerase efficiency and stereospecificity of the sex pheromone biosynthetic short-chain dehydrogenases/reductases of Nasonia.

Project description:Males of the parasitic wasp genus Nasonia use blends of chiral hydroxylactones as sex pheromones to attract conspecific females. Whereas all Nasonia species use a mixture of (4R,5S)-5-hydroxy-4-decanolide (RS) and 4-methylquinazoline (MQ) as sex pheromones, Nasonia vitripennis evolved (4R,5R)-5-hydroxy-4-decanolide (RR) as an extra sex pheromone component. We recently identified and functionally characterized three short-chain dehydrogenases/reductases (SDRs) NV10127, NV10128, and NV10129 that are capable of catalyzing the epimerization of RS to RR via (4R)-5-oxo-4-decanolide (ODL) as intermediate. Despite their very high sequence identities of 88-98%, these proteins differ drastically in their ability to epimerize RS to RR and in their stereoselectivity when reducing ODL to RR/RS. Here, in order to unravel the sequence differences underlying these varying functional properties of NV1027, NV10128 and NV10129, we created chimeras of the three enzymes and monitored their catalytic activities in vitro. The results show that a few amino acid changes at the C-termini and active sites of Nasonia vitripennis SDRs lead to substantially altered RS to RR epimerization and ODL-reduction activities. Thus, our study adds to the understanding of pheromone evolution by showing that subtle mutations in key biosynthetic enzymes can result in drastic effects on the composition of chemical signals.

| S-EPMC6344473 | biostudies-literature

Preliminary observations on alcohol dehydrogenases in Comamonas terrigena that exhibit stereospecificity towards secondary alcohols.

Project description:Extracts of the cells of Comamonas terrigena, grown under a variety of different conditions, contain two distinct, constitutive, NAD-dependent alcohol dehydrogenase enzymes that can be separated by polyacrylamide-gel electrophoresis. One of the enzymes exhibits activity towards D-alkan-2-ols and primary alcohols and the other is active towards L-alkan-2-ols, symmetrical secondary alcohols and probably other positional isomers of secondary alcohols of the L-configuration. Methods for the individual assay of the two enzymes have been developed and have been used to define some of their general properties. Most of the substrates for these enzymes would not support growth of C. terrigena under the experimental conditions used and were relatively poorly oxidized by resting cell suspensions.

| S-EPMC1162454 | biostudies-other

Structural basis of the stereospecificity of bacterial B12-dependent 2-hydroxyisobutyryl-CoA mutase.

Project description:Bacterial coenzyme B12-dependent 2-hydroxyisobutyryl-CoA mutase (HCM) is a radical enzyme catalyzing the stereospecific interconversion of (S)-3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA. It consists of two subunits, HcmA and HcmB. To characterize the determinants of substrate specificity, we have analyzed the crystal structure of HCM from Aquincola tertiaricarbonis in complex with coenzyme B12 and the substrates (S)-3-hydroxybutyryl- and 2-hydroxyisobutyryl-CoA in alternative binding. When compared with the well studied structure of bacterial and mitochondrial B12-dependent methylmalonyl-CoA mutase (MCM), HCM has a highly conserved domain architecture. However, inspection of the substrate binding site identified amino acid residues not present in MCM, namely HcmA Ile(A90) and Asp(A117). Asp(A117) determines the orientation of the hydroxyl group of the acyl-CoA esters by H-bond formation, thus determining stereospecificity of catalysis. Accordingly, HcmA D117A and D117V mutations resulted in significantly increased activity toward (R)-3-hydroxybutyryl-CoA. Besides interconversion of hydroxylated acyl-CoA esters, wild-type HCM as well as HcmA I90V and I90A mutant enzymes could also isomerize pivalyl- and isovaleryl-CoA, albeit at >10 times lower rates than the favorite substrate (S)-3-hydroxybutyryl-CoA. The nonconservative mutation HcmA D117V, however, resulted in an enzyme showing high activity toward pivalyl-CoA. Structural requirements for binding and isomerization of highly branched acyl-CoA substrates such as 2-hydroxyisobutyryl- and pivalyl-CoA, possessing tertiary and quaternary carbon atoms, respectively, are discussed.

| S-EPMC4392272 | biostudies-literature

Plant Science View on Biohybrid Development.

Project description:Biohybrid consists of a living organism or cell and at least one engineered component. Designing robot-plant biohybrids is a great challenge: it requires interdisciplinary reconsideration of capabilities intimate specific to the biology of plants. Envisioned advances should improve agricultural/horticultural/social practice and could open new directions in utilization of plants by humans. Proper biohybrid cooperation depends upon effective communication. During evolution, plants developed many ways to communicate with each other, with animals, and with microorganisms. The most notable examples are: the use of phytohormones, rapid long-distance signaling, gravity, and light perception. These processes can now be intentionally re-shaped to establish plant-robot communication. In this article, we focus on plants physiological and molecular processes that could be used in bio-hybrids. We show phototropism and biomechanics as promising ways of effective communication, resulting in an alteration in plant architecture, and discuss the specifics of plants anatomy, physiology and development with regards to the bio-hybrids. Moreover, we discuss ways how robots could influence plants growth and development and present aims, ideas, and realized projects of plant-robot biohybrids.

| S-EPMC5558049 | biostudies-other

Review of glucose oxidases and glucose dehydrogenases: a bird's eye view of glucose sensing enzymes.

Project description:The evolution from first-generation through third-generation glucose sensors has witnessed the appearance of a number of very diverse oxidoreductases, which vary tremendously in terms of origin, structure, substrate specificity, cofactor used as primary electron acceptor, and acceptable final electron acceptor. This article summarizes our present knowledge of redox enzymes currently utilized in commercially available glucose monitoring systems to promote a fuller appreciation of enzymatic properties and principles employed in blood glucose monitoring to help avoid potential errors.

| S-EPMC3208862 | biostudies-literature

Structural and Phylogenetic Diversity of Anaerobic Carbon-Monoxide Dehydrogenases.

Project description:Anaerobic Ni-containing carbon-monoxide dehydrogenases (Ni-CODHs) catalyze the reversible conversion between carbon monoxide and carbon dioxide as multi-enzyme complexes responsible for carbon fixation and energy conservation in anaerobic microbes. However, few biochemically characterized model enzymes exist, with most Ni-CODHs remaining functionally unknown. Here, we performed phylogenetic and structure-based Ni-CODH classification using an expanded dataset comprised of 1942 non-redundant Ni-CODHs from 1375 Ni-CODH-encoding genomes across 36 phyla. Ni-CODHs were divided into seven clades, including a novel clade. Further classification into 24 structural groups based on sequence analysis combined with structural prediction revealed diverse structural motifs for metal cluster formation and catalysis, including novel structural motifs potentially capable of forming metal clusters or binding metal ions, indicating Ni-CODH diversity and plasticity. Phylogenetic analysis illustrated that the metal clusters responsible for intermolecular electron transfer were drastically altered during evolution. Additionally, we identified novel putative Ni-CODH-associated proteins from genomic contexts other than the Wood-Ljungdahl pathway and energy converting hydrogenase system proteins. Network analysis among the structural groups of Ni-CODHs, their associated proteins and taxonomies revealed previously unrecognized gene clusters for Ni-CODHs, including uncharacterized structural groups with putative metal transporters, oxidoreductases, or transcription factors. These results suggested diversification of Ni-CODH structures adapting to their associated proteins across microbial genomes.

| S-EPMC6344411 | biostudies-literature

Structural determinants of inhibitor selectivity in prokaryotic IMP dehydrogenases.

Project description:The protozoan parasite Cryptosporidium parvum is a major cause of gastrointestinal disease; no effective drug therapy exists to treat this infection. Curiously, C. parvum IMPDH (CpIMPDH) is most closely related to prokaryotic IMPDHs, suggesting that the parasite obtained its IMPDH gene via horizontal transfer. We previously identified inhibitors of CpIMPDH that do not inhibit human IMPDHs. Here, we show that these compounds also inhibit IMPDHs from Helicobacter pylori, Borrelia burgdorferi, and Streptococcus pyogenes, but not from Escherichia coli. Residues Ala165 and Tyr358 comprise a structural motif that defines susceptible enzymes. Importantly, a second-generation CpIMPDH inhibitor has bacteriocidal activity on H. pylori but not E. coli. We propose that CpIMPDH-targeted inhibitors can be developed into a new class of antibiotics that will spare some commensal bacteria.

| S-EPMC2991053 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data