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Applied Microbiology and Biotechnology Jan 2019Natural rubber (NR), poly(cis-1,4-isoprene), is used in an industrial scale for more than 100 years. Most of the NR-derived materials are released to the environment as... (Review)
Review
Natural rubber (NR), poly(cis-1,4-isoprene), is used in an industrial scale for more than 100 years. Most of the NR-derived materials are released to the environment as waste or by abrasion of small particles from our tires. Furthermore, compounds with isoprene units in their molecular structures are part of many biomolecules such as terpenoids and carotenoids. Therefore, it is not surprising that NR-degrading bacteria are widespread in nature. NR has one carbon-carbon double bond per isoprene unit and this functional group is the primary target of NR-cleaving enzymes, so-called rubber oxygenases. Rubber oxygenases are secreted by rubber-degrading bacteria to initiate the break-down of the polymer and to use the generated cleavage products as a carbon source. Three main types of rubber oxygenases have been described so far. One is rubber oxygenase RoxA that was first isolated from Xanthomonas sp. 35Y but was later also identified in other Gram-negative rubber-degrading species. The second type of rubber oxygenase is the latex clearing protein (Lcp) that has been regularly found in Gram-positive rubber degraders. Recently, a third type of rubber oxygenase (RoxB) with distant relationship to RoxAs was identified in Gram-negative bacteria. All rubber oxygenases described so far are haem-containing enzymes and oxidatively cleave polyisoprene to low molecular weight oligoisoprenoids with terminal CHO and CO-CH functions between a variable number of intact isoprene units, depending on the type of rubber oxygenase. This contribution summarises the properties of RoxAs, RoxBs and Lcps.
Topics: Bacteria; Bacterial Proteins; Biotechnology; Electron Spin Resonance Spectroscopy; Heme; Hemiterpenes; Latex; Oxygenases; Phylogeny; Rubber; Spectrophotometry, Ultraviolet; Xanthomonas
PubMed: 30377752
DOI: 10.1007/s00253-018-9453-z -
Annual Review of Microbiology Sep 2022Oxygenases, which catalyze the reductive activation of O and incorporation of oxygen atoms into substrates, are widely distributed in aerobes. They function by switching... (Review)
Review
Oxygenases, which catalyze the reductive activation of O and incorporation of oxygen atoms into substrates, are widely distributed in aerobes. They function by switching the redox states of essential cofactors that include flavin, heme iron, Rieske non-heme iron, and Fe(II)/α-ketoglutarate. This review summarizes the catalytic features of flavin-dependent monooxygenases, heme iron-dependent cytochrome P450 monooxygenases, Rieske non-heme iron-dependent oxygenases, Fe(II)/α-ketoglutarate-dependent dioxygenases, and ring-cleavage dioxygenases, which are commonly involved in pesticide degradation. Heteroatom release (hydroxylation-coupled hetero group release), aromatic/heterocyclic ring hydroxylation to form ring-cleavage substrates, and ring cleavage are the main chemical fates of pesticides catalyzed by these oxygenases. The diversity of oxygenases, specificities for electron transport components, and potential applications of oxygenases are also discussed. This article summarizes our current understanding of the catalytic mechanisms of oxygenases and a framework for distinguishing the roles of oxygenases in pesticide degradation.
Topics: Dioxygenases; Ferrous Compounds; Flavins; Iron; Ketoglutaric Acids; Mixed Function Oxygenases; Oxygenases; Pesticides
PubMed: 35650666
DOI: 10.1146/annurev-micro-041320-091758 -
Annual Review of Biochemistry Jun 20182-Oxoglutarate (2OG)-dependent oxygenases (2OGXs) catalyze a remarkably diverse range of oxidative reactions. In animals, these comprise hydroxylations and... (Review)
Review
2-Oxoglutarate (2OG)-dependent oxygenases (2OGXs) catalyze a remarkably diverse range of oxidative reactions. In animals, these comprise hydroxylations and N-demethylations proceeding via hydroxylation; in plants and microbes, they catalyze a wider range including ring formations, rearrangements, desaturations, and halogenations. The catalytic flexibility of 2OGXs is reflected in their biological functions. After pioneering work identified the roles of 2OGXs in collagen biosynthesis, research revealed they also function in plant and animal development, transcriptional regulation, nucleic acid modification/repair, fatty acid metabolism, and secondary metabolite biosynthesis, including of medicinally important antibiotics. In plants, 2OGXs are important agrochemical targets and catalyze herbicide degradation. Human 2OGXs, particularly those regulating transcription, are current therapeutic targets for anemia and cancer. Here, we give an overview of the biochemistry of 2OGXs, providing examples linking to biological function, and outline how knowledge of their enzymology is being exploited in medicine, agrochemistry, and biocatalysis.
Topics: Animals; Biocatalysis; Collagen; Humans; Hydroxylation; Ketoglutaric Acids; Models, Biological; Models, Molecular; Oxidation-Reduction; Oxygenases; Protein Conformation; Substrate Specificity
PubMed: 29494239
DOI: 10.1146/annurev-biochem-061516-044724 -
Topics in Current Chemistry 1979
Review
Topics: Amino Acids; Bacteria; Catechols; Circular Dichroism; Heme; Hydroxybenzoates; Molecular Weight; Oxygenases; Protein Conformation; Protocatechuate-3,4-Dioxygenase; Pseudomonas; Substrate Specificity; Tryptophan Oxygenase
PubMed: 375466
DOI: 10.1007/BFb0048193 -
Briefings in Functional Genomics Jan 2020A plant communicates within itself and with the outside world by deploying an array of agents that include several attractants by virtue of their color and smell. In... (Review)
Review
A plant communicates within itself and with the outside world by deploying an array of agents that include several attractants by virtue of their color and smell. In this category, the contribution of 'carotenoids and apocarotenoids' is very significant. Apocarotenoids, the carotenoid-derived compounds, show wide representation among organisms. Their biosynthesis occurs by oxidative cleavage of carotenoids, a high-value reaction, mediated by carotenoid cleavage oxygenases or carotenoid cleavage dioxygenases (CCDs)-a family of non-heme iron enzymes. Structurally, this protein family displays wide diversity but is limited in its distribution among plants. Functionally, this protein family has been recognized to offer a role in phytohormones, volatiles and signal production. Further, their wide presence and clade-specific functional disparity demands a comprehensive account. This review focuses on the critical assessment of CCDs of higher plants, describing recent progress in their functional aspects and regulatory mechanisms, domain architecture, classification and localization. The work also highlights the relevant discussion for further exploration of this multi-prospective protein family for the betterment of its functional understanding and improvement of crops.
Topics: Carotenoids; Gene Expression Regulation, Plant; Oxygenases; Plant Development; Plant Proteins; Plants; Structure-Activity Relationship
PubMed: 31875900
DOI: 10.1093/bfgp/elz037 -
Biochimica Et Biophysica Acta.... Nov 2020The carotenoids are terpenoid fat-soluble pigments produced by plants, algae, and several bacteria and fungi. They are ubiquitous components of animal diets. Carotenoid... (Review)
Review
The carotenoids are terpenoid fat-soluble pigments produced by plants, algae, and several bacteria and fungi. They are ubiquitous components of animal diets. Carotenoid cleavage oxygenase (CCO) superfamily members are involved in carotenoid metabolism and are present in all kingdoms of life. Throughout the animal kingdom, carotenoid oxygenases are widely distributed and they are completely absent only in two unicellular organisms, Monosiga and Leishmania. Mammals have three paralogs 15,15'-β-carotene oxygenase (BCO1), 9',10'-β-carotene oxygenase (BCO2) and RPE65. The first two enzymes are classical carotenoid oxygenases: they cleave carbon‑carbon double bonds and incorporate two atoms of oxygen in the substrate at the site of cleavage. The third, RPE65, is an unusual family member, it is the retinoid isomerohydrolase in the visual cycle that converts all-trans-retinyl ester into 11-cis-retinol. Here we discuss evolutionary aspects of the carotenoid cleavage oxygenase superfamily and their enzymology to deduce what insight we can obtain from their evolutionary conservation.
Topics: Animals; Carotenoids; Dioxygenases; Evolution, Molecular; Lipid Metabolism; Mammals; Oxygenases; beta-Carotene 15,15'-Monooxygenase; cis-trans-Isomerases
PubMed: 32061750
DOI: 10.1016/j.bbalip.2020.158665 -
Journal of Biological Inorganic... Apr 2017A wide range of spectroscopic approaches have been used to interrogate the mononuclear iron metallocenter in 2-oxoglutarate (2OG)-dependent oxygenases. The results from... (Review)
Review
A wide range of spectroscopic approaches have been used to interrogate the mononuclear iron metallocenter in 2-oxoglutarate (2OG)-dependent oxygenases. The results from these spectroscopic studies have provided valuable insights into the structural changes at the active site during substrate binding and catalysis, thus providing critical information that complements investigations of these enzymes by X-ray crystallography, biochemical, and computational approaches. This mini-review highlights taurine hydroxylase (taurine:2OG dioxygenase, TauD) as a case study to illustrate the wealth of knowledge that can be generated by applying a diverse array of spectroscopic investigations to a single enzyme. In particular, electronic absorption, circular dichroism, magnetic circular dichroism, conventional and pulse electron paramagnetic, Mössbauer, X-ray absorption, and resonance Raman methods have been exploited to uncover the properties of the metal site in TauD.
Topics: Mixed Function Oxygenases; Spectrum Analysis
PubMed: 27812832
DOI: 10.1007/s00775-016-1406-3 -
Accounts of Chemical Research Oct 2014Biosynthesis of bioactive natural products frequently features oxidation at multiple sites. Starting from a relatively reduced chemical scaffold that is assembled by... (Review)
Review
Biosynthesis of bioactive natural products frequently features oxidation at multiple sites. Starting from a relatively reduced chemical scaffold that is assembled by controlled polymerization of small precursors, for example, acetate or amino acids, a diverse range of redox reactions can generate very complex and highly oxygenated structures. Their formation often involves C-H activation reactions catalyzed by oxygenase enzymes, either monooxygenases or dioxygenases. The former category includes the cytochrome P450s and flavin-dependent oxygenases, whereas examples of the latter are the non-heme iron α-ketoglutarate-dependent oxygenases. Oxygenases can catalyze a plethora of reactions ranging from hydroxylations and epoxidations to dehydrogenations, cyclizations, and rearrangements. The specific transformations are usually possible only with the use of these enzymatic catalysts. Aside from the ability of oxygenases to specifically oxidize unactivated carbon skeletons, some have recently been demonstrated to possess a fascinating ability to catalyze multiple reactions in a highly ordered fashion at different sites starting with a single substrate molecule. In the past, oxygenases associated with secondary metabolite pathways were considered to be highly regio-, stereo-, and substrate specific, with one oxidizing enzyme encoded in the gene cluster corresponding to one oxidation location in the natural product itself. However, it is becoming progressively clear that this "one oxygenase, one oxidation site" relationship is not necessarily a valid assumption. Multifunctional oxidases are known to occur in higher plants, fungi, and bacteria. Natural product gene clusters that contain multifunctional oxidase enzymes are responsible for production of lovastatin (a cholesterol-lowering agent and precursor to simvastatin), scopolamine (an anticholinergic drug), and cytochalasin E (an angiogenesis inhibitor), among many others. As opposed to simply being substrate promiscuous, these enzymes show very high substrate specificity and catalyze several oxidative reactions in a single pathway, with each oxidation being a prerequisite for the next. The basis for their specificity and highly ordered sequence is not yet well understood. In the lovastatin pathway, LovA is a cytochrome P450 that introduces a double bond and a hydroxyl group. H6H is an α-ketoglutarate-dependent oxygenase that hydroxylates (-)-atropine and then closes the newly introduced oxygen onto a neighboring methylene to generate the epoxide of scopolamine. CcsB is a flavin-dependent Baeyer-Villigerase that converts a ketone to a carbonate by double oxidation, a reaction not possible without enzymes. Recent crystallographic studies of other multifunctional oxygenases, such as AurH, a cytochrome P450 from Streptomyces thioluteus involved in aureothin biosynthesis, have indicated a steric switch mechanism. After the initial hydroxylation reaction catalyzed by AurH, the enzyme is thought to undergo a substrate-induced conformational change. In this Account, advances in our knowledge of these fascinating multifunctional enzymes and their potential will be explored.
Topics: Biological Products; Molecular Structure; Oxygenases; Secondary Metabolism
PubMed: 25250512
DOI: 10.1021/ar500242c -
Current Opinion in Chemical Biology Apr 2002Oxygenase enzymes have seen limited practical applications because of their complexity, poor stabilities, and often low catalytic rates. However, their ability to... (Review)
Review
Oxygenase enzymes have seen limited practical applications because of their complexity, poor stabilities, and often low catalytic rates. However, their ability to perform difficult chemistry with high selectivity and specificity has kept oxygenases at the forefront of engineering efforts. Growing understanding of structure-function relationships and improved protein engineering methods are paving the way for applications of oxygenases in chemical synthesis and bioremediation.
Topics: Animals; Catalysis; Directed Molecular Evolution; Humans; Oxygenases; Protein Engineering
PubMed: 12038995
DOI: 10.1016/s1367-5931(02)00305-8 -
Molecules (Basel, Switzerland) Apr 2020Abundant in nature, carotenoids are a class of fat-soluble pigments with a polyene tetraterpenoid structure. They possess antioxidant properties and their consumption...
Abundant in nature, carotenoids are a class of fat-soluble pigments with a polyene tetraterpenoid structure. They possess antioxidant properties and their consumption leads to certain health benefits in humans. Carotenoid cleavage oxygenases (CCOs) are a superfamily of enzymes which oxidatively cleave carotenoids and they are present in all kingdoms of life. Complexity of CCO evolution is high. For example, in this study we serendipitously found a new family of eukaryotic CCOs, the apocarotenoid oxygenase-like (ACOL) family. This family has several members in animal genomes and lacks the animal-specific amino acid motif PDPCK. This motif is likely to be associated with palmitoylation of some animal CCOs. We recently demonstrated that two mammalian members of the carotenoid oxygenase family retinal pigment epithelial-specific 65 kDa protein (RPE65) and beta-carotene oxygenase 2 (BCO2) are palmitoylated proteins. Here we used the acyl-resin-assisted capture (acyl-RAC) method to demonstrate protein palmitoylation and immunochemistry to localize mouse BCO2 (mBCO2) in COS7 cell line in the absence and presence of its substrate β-carotene. We demonstrate that mBCO2 palmitoylation depends on the evolutionarily conserved motif PDPCK and that metazoan family members lacking the motif (Lancelet beta-carotene oxygenase-like protein (BCOL) and Acropora ACOL) are not palmitoylated. Additionally, we observed that the palmitoylation status of mBCO2 and its membrane association depend on the presence of its substrate β-carotene. Based on our results we conclude that most metazoan carotenoid oxygenases retain the evolutionarily conserved palmitoylation PDPCK motif to target proteins to internal membranes depending on substrate status. Exceptions are in the secreted BCOL subfamily and the strictly cytosolic ancient ACOL subfamily of carotenoid oxygenases.
Topics: Animals; Carotenoids; Dioxygenases; Fatty Acids, Monounsaturated; Fluorescent Antibody Technique; Humans; Mice; Multigene Family; Mutation; Oxygenases; Phylogeny; Protein Transport; Substrate Specificity
PubMed: 32331396
DOI: 10.3390/molecules25081942