Epoxide hydrolase and its application in organic synthesis

International audienceOrganic chemists have become interested in enzymes as catalysts due to their high efficiencies and specificities. Moreover, recent progress in molecular biology and enzyme-related research areas enabled and simplified the production and purification of recombinant enzymes in large quantities and their engineering towards tailor-made biocatalysts using straightforward mutagenesis and screening techniques. This is also true for epoxide hydrolases (EHs), as evidenced by the many published research papers about the synthetic applications of naturally occurring or engineered EHs

Enantioselective Bio-Hydrolysis of Various Racemic and meso Aromatic Epoxides Using the Recombinant Epoxide Hydrolase Kau2

International audienceEpoxide hydrolase Kau2 overexpressed in Escherichia coli RE3 has been tested with ten different racemic and meso,-disubstituted aromatic epoxides. Some of the tested substrates were bi-functional, and most of them are very useful building blocks in synthetic chemistry applications. As a general trend Kau2 proved to be an extremely enantioselective biocatalyst, the diol products and remaining epoxides of the bioconversions being obtained – with two exceptions – in nearly enantiomerically pure form. Furthermore, the reaction times were usually very short (around 1 h, except when stilbene oxides were used), and the use of organic co-solvent was well tolerated, enabling very high substrate concentrations (up to 75 g/L) to be reached. Even extremely sterically demanding epoxides such as cis-and trans-stilbene oxides were transformed on a reasonable time scale. All reactions were successfully conducted on a 1-g preparative scale, generating diol-and epoxide-based chiral synthons with very high enantiomeric excesses and isolated yields close to the theoretical maximum. Thus we have here demonstrated the usefulness and versatility of lyophilizedEscherichia coli cells expressing Kau2 epoxide hydrolase as a highly enantioselective biocatalyst for accessing very valuable optically pure aromatic epoxides and diols through kinetic resolution of racemates or desymmetrization of meso epoxides

Gibbs Free Energy of Formation of Chlordecone and Potential Degradation Products: Implications for Remediation Strategies and Environmental Fate

International audienceChlordecone (C10Cl10O; CAS number 143-50-0) has been used extensively as an organochlorine insecticide, but is nowadays banned under The Stockholm Convention on Persistent Organic Pollutants (POPs). A search for chlordecone respiring organisms and choosing between reductive versus oxidative remediation tools and strategies to clean up chlordecone polluted environments would benefit from the availability of Gibbs free energy data of chlordecone and its potential dechlorination products. Presently such data are not available. Polycyclic "cage" molecules of which chlordecone is an example contain considerable strain energy. It is not a priory clear how this affects thermodynamic properties of the chlorinated members of this unique class of compounds, and to what extent redox potentials for the halogenated congeners are different from those of other aliphatic and aromatic organohalogens. We have performed ab initio quantum chemical calculations to estimate ΔfHmo and ΔfGmo values of chlordecone and selected dechlorination products, and used these data to calculate their Gibbs free energy and redox potential. With redox potentials in the range of 336 to 413 mV chlordecone has an Eo' value similar to that of other organochlorines. The results indicate that there are no thermodynamic reasons why chlordecone respiring or fermenting organisms should not exist

Approche théorique de la biodégradation de la chlordécone

International audienceChlordecone (CLD) is an organochlorine insecticide that was used from 1972 to 1993 in the French West Indies (FWI) to control the populations of black weevil in banana plantations. This pesticide, with recognized neurotoxic, endrocrine, reproductive and carcinogenic effects, is nowadays responsible of an unprecedented sanitary, economic and social crisis in FWI. Thanks to the management options taken in the past years by the authorities to avoid the population dietary exposure the crisis is fortunately essentially contained. A final solution to the problem would consist however to eliminate the source of CLD responsible for the diffuse pollution of all the FWI environmental compartments and related food resources and so to destroy the stock of CLD still presents in the soils. One of the cheapest and most environmental friendly destruction methods corresponds to microbial degradation. Such a mode of destruction seems to be particularly appropriate in the case of FWI since it can often be implemented in situ, using techniques (e.g., watering; addition of nutrients, labile organic matter, microorganisms) that are fairly easy to incorporate into existing agricultural practices. The latter is important as the pollution is estimated to cover some 19,000 ha of arable lands. Until now however there is no evidence of natural attenuation in the environments impacted by chlordecone and so of the possibility to stimulate the rate of the process. The reason usually advocated to explain this apparent absence of degradation in the environment is the peculiar chemical structure of CLD (bishomocubane “cage” structure with a high steric hindrance caused by the 10 chlorine atoms bound to the cage), coupled to its low aqueous solubility (3 mg/l at 20°C) and high hydrophobicity (Log Kow 20°C, pH 7 = 4.5) that would make it refractory to degradation. In this chapter through a thermodynamic approach, we demonstrate that there is no energetic reason why the structure of CLD should not be amenable to microbial degradation and we propose some possible reasons for the apparent absence of CLD degradation in FWI and what could be done to reverse the situation.La chlordécone (CLD) est un insecticide organochloré utilisé de 1972 à 1993 dans les Antilles françaises pour lutter contre les populations de charançon noir dans les bananeraies. Ce pesticide, aux effets neurotoxiques, endocriniens, reproductifs et cancérigènes reconnus, est actuellement responsable d’une crise sanitaire, économique et sociale sans précédent en Guadeloupe et en Martinique. Grâce aux options de gestion prises ces dernières années par les autorités pour éviter l'exposition alimentaire de la population, la crise est heureusement essentiellement contenue. Une solution définitive au problème consisterait à éliminer la source de CLD responsable de la pollution diffuse de tous les compartiments environnementaux des Antilles et des ressources alimentaires associées et donc à détruire le stock de CLD encore présent dans les sols. L'une des méthodes de destruction les moins chères et les plus respectueuses de l'environnement correspond à la dégradation microbienne. Un tel mode de destruction semble être particulièrement approprié au cas des Antilles, car il peut souvent être mis en œuvre in situ, en utilisant des techniques (par exemple, arrosage; ajout d'éléments nutritifs, matière organique labile, microorganismes) qui sont assez faciles à intégrer aux pratiques agricoles existantes. Ce dernier point est important car on estime que la pollution couvre environ 19 000 ha de terres arables. Jusqu'à présent cependant, il n'y avait aucune preuve d'atténuation naturelle dans les environnements affectés par la chlordécone et donc de la possibilité de stimuler le rythme du processus. La raison généralement invoquée pour expliquer cette apparente absence de dégradation dans l’environnement est la structure chimique particulière de la CLD (structure en forme de «cage» bishomocubane avec un fort encombrement stérique causé par les 10 atomes de chlore liés à la cage), couplée à sa faible solubilité dans l’eau (3 mg / l à 20 ° C) et une hydrophobie élevée (Log Kow 20 ° C, pH 7 = 4,5) qui la rendraient réfractaire à la dégradation. Dans ce chapitre, au moyen d'une approche thermodynamique, nous démontrons qu’aucune raison énergétique ne justifie que la structure de la CLD ne soit pas accessible à une dégradation microbienne et nous proposons des raisons possibles à l’absence apparente de dégradation de la CLD aux Antilles et ce qui pourrait être fait pour inverser la situation

Biocatalytic Potential of the Epoxide Hydrolase from Agrobacterium radiobacter AD1 and a Mutant with Enhanced Enantioselectivity

Optically pure epoxides are useful synthons for a variety of biologically active compounds. The epoxide hydrolase obtained from Agrobacterium radiobacter AD1 hydrolyses racemic aryl epoxides with moderate and aliphatic epoxides with low enantioselectivity. The three-dimensional structure of this enzyme indicates that two tyrosine residues interact with the epoxide oxygen. Mutating one of these, tyrosine 215, to a phenylalanine (Y215F) resulted in an enzyme with increased enantioselectivity towards aryl epoxides. The relatively strong decrease in activity towards the remaining enantiomers makes this enzyme a much better biocatalyst than the wild-type enzyme for the preparation of optically pure (S)-styrene oxide derivatives.

Silica-Catalysed and Highly Stereoselective Convergent and Nonconvergent Rearrangements of Menthone Enol Acetate Epoxides: Easy Access to the Four α-Hydroxymenthone Stereoisomers

International audienc

Correction to Gibbs Free Energy of Chlordecone and Potential Degradation Products: Implications for Remediation Strategies and Environmental Fate

Correction to Gibbs Free Energy of Chlordecone and Potential Degradation Products: Implications for Remediation Strategies and Environmental Fat