Epoxide microbial

Ensign SA, FJ Smakk, JR Allen, MK Sluis (1998) New roles for COj in the microbial metabolism of aliphatic epoxides and ketones. Arch Microbiol 169 179-187. 

Another very recent development in the field of enzymatic domino reactions is a biocatalytic hydrogen-transfer reduction of halo ketones into enantiopure epoxides, which has been developed by Faber, Bornscheuer and Kroutil. Interestingly, the reaction was carried out with whole lyophilized microbial cells at pH ca. 13. Investigations using isolated enzymes were not successful, as they lost their activity under these conditions [26]. 

Gong, P.-F. and Xu, J.-H. (2005) Bio-resolution of a chiral epoxide using whole cells of Bacillus megaterium ECU1001 in a biphasic system. Enzyme and Microbial Technology, 36, 252-257. 

Prichanont, S., Leak, D.J. and Stuckey, D.C. (1998) Alkene monooxygenase-catalyzed whole cell epoxidation in a two-liquid phase system. Enzyme and Microbial Technology, 22 (6), 471 479. 

The interdigital secretion of the red hartebeest, A. b. caama, consists of fewer compound classes. It contains a few alkanes and short-chain, branched alcohols, fatty acids, including a few of the higher fatty acids up to octadecanoic acid, an epoxide and the cyclic ethers, rans-(2 ,5.R)-furanoid linalool oxide 23, as-(2JR,5S)-furanoid linalool oxide 24 and ds-(2S,5i )-furanoid linalool oxide 25 (Fig. 5) in a ratio of 2.5 1 1.5 respectively [138]. From the point of view that many of the constituents of the interdigital secretion of this animal are probably of microbial origin, it is interesting that cis- and trans- furanoid linalool oxides have also been found in castoreum [77]. 

With this system we converted 135 mM styrene (relative to the total liquid volume) to styrene oxide in 10 h at a cell dry weight of around lOg/L aqueous phase, with an average activity of 152 U/L total liquid volume. This corresponds to a space-time yield of 1.1 g (5)-styrene oxide per liter and hour. These are the highest specific activities reported thus far for a microbial epoxidation process. ... 

In spite of the potential interest of such enzymes for fine chemical synthesis, it was only recently that a detailed search for epoxide hydrolases from microbial... 

One of the first applications of the microbial hydrolysis of epoxides for the synthesis of a bioactive compound is based on the resolution of a 2,3-disub-stituted oxirane having a cis-configuration (Scheme 14). Thus, by using an enzyme preparation derived from Pseudomonas sp., the (91 ,10S)-enantiomer was hydrolyzed in a frans-specific fashion (i.e. via inversion of configuration at C-10) yielding the 9R,10R)-threo-diol. The remaining (9S,101 )-epoxide was converted into (-1-)-dispar lure, the sex pheromone of the gypsy moth in >95% ee [101]. 

Heptachlor rapidly degraded when incubated with acclimated, mixed microbial cultures under aerobic conditions. After 4 wk, 95.3% of the applied dosage was removed (Leigh, 1969). In a mixed bacterial culture under aerobic conditions, heptachlor was transformed to chlordene, 1-hydroxychlordene, heptachlor epoxide, and chlordene epoxide in low yields (Miles et al, 1971). Heptachlor rapidly degraded when incubated with acclimated, mixed microbial cultures under aerobic conditions. After 4 wk, 95.3% of the applied dosage was removed (Leigh, 1969). 

The mono-oxygenases which catalyse a series of oxidations such as hydroxylation, epoxidation, heteroatom oxidation and Baeyer-Villiger oxidation (Figure 2.24), depend on NADH or NADPH and cofactors usually Fe or Cu. A particularly important reaction is the direct incorporation of molecular oxygen into non-activated carbon centres, such as in synthesis of important steroidal drags by microbial 11 dr-hydroxylation of... 

Enzymic asynmietric epoxidation of alkenes may be performed by pure monooxygenases. However, due to practical problems such as need of cofactors, microbial oxidation with whole cells has been more widely used for the purpose. One great disadvantage however, is the toxicity of epoxides towards living cells. 

Asymmetric microbial oxidation afforded the (-)-epoxide which has been explored as a building block ring opening reactions with organometallic nucleophiles, and via Friedel-Crafts reactions have been reported. [226,227]. A non-biotransformative approach to this epoxide has also been described [228]. Copper(II)-catalysed oxidative hydrolysis (Eq. 72) affords a lactic acid analogue in high enantiomeric purity [229]. 

Rosenkranz, H.S. Poirier, L.A. (1979) Evaluation of the mutagenicity and DNA-modifying activity of carcinogens and noncarcinogens in microbial systems. J. natl Cancer Inst., 62, 873-892 Ross, A.M., Pohl, T.M., Piazza K., Thomas, M., Fox, B. Whalen, D.L. (1982) Vinyl epoxide... 

Methyl-5-hepten-2-one is a valuable precursor for microbial epoxidations and hence the production of chiral ethers with high optical purities. The biotransformation of 6-methyl-5-hepten-2-one (33) by Botryodiplodia malorum CBS 13450 to (/ )-sulcatol (84) was described [61], which is then epoxidised to the (55)-epoxide (85) and opened intramolecularly to cis-(2R,5R)-2-(2 -hydroxyisopropyl)-5-methyltetra-hydrofuran (86) and c/s-(35,67 )-3-hydroxy-2,2,6-trimethyltetrahydropyran (87). Reduction of 6-methyl-5-hepten-2-one (33) with baker s yeast to (5)-sulcatol (88) which was used as substrate for Kloeckera corticis... 

More recently, the degradation of a-pinene by Pseudomonas jluorescens NCIMB 11671 was described [97,98]. A novel pathway for the microbial breakdown of a-pinene (119) was proposed, Fig. (23). The attack is initiated by enzymatic oxygenation of the 1,2-double bond to form the epoxide (127). This epoxide then undergoes rapid rearrangement to produce a novel diunsaturated aldehyde, occurring as two isomeric forms. The primary product of the reaction (Z)-2-methyl-5-isopropylhexa-2,5-dien-l-al (trivial name isonovalal) (128) can undergo chemical isomerisation to the -form (novalal) (129). Isonovalal, the native form of... 

Microbially produced (2.S .3.S )-// .v-dihvdroxy-2.3-dihvdrobenzoic acid was used in the synthesis of enf-streptol, enf-senepoxide, and /so-crotepoxide (Fig. 33). The short and efficient synthesis of these biologically active compounds included the esterification of the carboxylic acid and protection of the diol moiety, delivering control of the regio- and stereoselectivity of the following epoxidation or dihydrox-ylation steps [178, 180]. 

Active hits were found for every type of substrate screened, including those for which other known microbial epoxide hydrolases were ineffective. For example, hydrolysis of m-stilbenc oxide was not successful with several microbial EHs tested previously.4243 By contrast, several of our new enzymes actively hydrolyzed this substrate and exhibited excellent enantioselectivities (>99% ee). It is important to note that these enzymes were found to be capable of selectively hydrolyzing a wide range of mc.vo-cpoxidcs, including cyclic and acyclic alkyl- and aryl-substituted substrates. 

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