Carbon biotransformations

In principle, numerous reports have detailed the possibility to modify an enzyme to carry out a different type of reaction than that of its attributed function, and the possibility to modify the cofactor of the enzyme has been well explored [8,10]. Recently, the possibility to directly observe reactions, normally not catalyzed by an enzyme when choosing a modified substrate, has been reported under the concept of catalytic promiscuity [9], a phenomenon that is believed to be involved in the appearance of new enzyme functions during the course of evolution [23]. A recent example of catalytic promiscuity of possible interest for novel biotransformations concerns the discovery that mutation of the nucleophilic serine residue in the active site of Candida antarctica lipase B produces a mutant (SerlOSAla) capable of efficiently catalyzing the Michael addition of acetyl acetone to methyl vinyl ketone [24]. The oxyanion hole is believed to be complex and activate the carbonyl group of the electrophile, while the histidine nucleophile takes care of generating the acetyl acetonate anion by deprotonation of the carbon (Figure 3.5). 

A related situation is found in the case of P-substituted cycloketones here, the electronic difference between the two a-carbons is almost insignificant, resulting in unselective migration upon chemical oxidation. BVMOs have a particularly different behavior, as they can influence the stereo- and/or regioselectivity of the biooxidation. In the latter case, the distribution of proximal and distal lactones is affected by directing the oxygen insertion process either into the bond close or remote to the position of the P-substituent. Consequently, a regioisomeric excess (re) can be defined for this biotransformation, similar to enantiomeric excess or diastereomeric excess values [143]. 

Vogel TM, McCarty PL. 1985. Biotransformation of tetrachloroethylene to trichloroethylene, dichloroethylene, vinyl chloride and carbon dioxide imder methanogenic conditions. Appl Environ Microbiol 49 1080-1083. 

As mentioned in the introductory part, stereochemical course of the conversion of isocitric acid to a-ketoglutaric acid in TCA cycle is completely enantiose-lective although the reaction does not form an asymmetric carbon in the usual metabolic path. If such type of oxidative decarboxylation can be applied to synthetic compounds, it is expected that an entirely new type of asymmetric biotransformation will be developed. 

The biotransformation of methyl phenyl phosphonate to benzene by K. pneumoniae (Cook et al. 1979) (Figure 2.7a). Further examples of the cleavage of the carbon-phosphorus... 

Hasham SA, DL Freedman (1999) Enhanced biotransformation of carbon tetrachloride by Acetobacterium woodii upon addition of hydroxycobalamin and fructose. Appl Environ Microbiol 65 4537-4542. 

Somsamak P, HH Richnow, MM Haggblom (2005) Carbon isotope fractionation during anaerobic biotransformation of methyl fert-butyl ether and ferf-amyl methyl ether. Environ Sci Technol 39 103-109. 

Shih C-C, ME Davey, J Zhou, JM Tiedje, CS Criddle (1996) Effects of phenol feeding pattern on microbial community structure and cometabolism of trichloroethylene. Appl Environ Microbiol 62 2953-2960. Somsamak P, HH Richnow, MM Haggblom (2005) Carbon isotope fractionation during anaerobic biotransformation of methyl ferf-butyl ether and ferf-amyl methyl ether. Environ Sci Technol 39 103-109. Somsamak P, RM Cowan, MM Haggblom (2001) Anaerobic biotransformation of fuel oxygenates under sulfate-reducing conditions. EEMS Microbiol Ecol 37 259-264. 

ElSisi, A.E.D., Earnest, D.L. and Sipes, LG. (1993a). Vitamin-A potentiation of carbon tetrachloride hepatotoxicity -enhanced lipid peroxidation without enhanced biotransformation. Toxicol. Appl. Pharmacol. 119, 289-294. 

In some cases, microorganisms can transform a contaminant, but they are not able to use this compound as a source of energy or carbon. This biotransformation is often called co-metabolism. In co-metabolism, the transformation of the compound is an incidental reaction catalyzed by enzymes, which are involved in the normal microbial metabolism.33 A well-known example of co-metabolism is the degradation of (TCE) by methanotrophic bacteria, a group of bacteria that use methane as their source of carbon and energy. When metabolizing methane, methanotrophs produce the enzyme methane monooxygenase, which catalyzes the oxidation of TCE and other chlorinated aliphatics under aerobic conditions.34 In addition to methane, toluene and phenol have been used as primary substrates to stimulate the aerobic co-metabolism of chlorinated solvents. 

Van der Zee FP, Bisschops IAE, Lettinga G et al (2003) Activated carbon as an electron acceptor and redox mediator during the anaerobic biotransformation of azo dyes. Environ Sci Technol 37 402-408... 

Despite the diverse range of documented enzyme-catalyzed reactions, there are only certain types of transformations that have thus far emerged as synthetically useful. These reactions are the hydrolysis of esters, reduction/oxidation reactions, and the formation of carbon-carbon bonds. The first part of this chapter gives a brief overview by describing some examples of various biotransformations that can easily be handled and accessed by synthetic organic chemists. These processes are now attracting more and more attention from nonspecialists of enzymes. 

In the arena of carbon-carbon bond-forming reactions, obviously a central feature in synthetic organic chemistry, the number of nonbiocatalytic methods in regular use far outweighs the small portfolio of biotransformations that can be considered to be available for general employment. 

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