Biotransformations-bioconversions

During the last twenty years, biochemical reactions performed by microorganisms or catalyzed by microbial enzymes have been extensively evaluated from the viewpoint of synthetic organic chemistry, and as a consequence they have been shown to have a high potential for both theoretical and practical applications in synthetic chemistry. Many attempts to utilize biological reactions for practical synthetic processes have been made - for example, for the preparation of pharmaceuticals, fine chemicals, food additives, and commodity chemicals. Such synthetic technology is called microbial transformation, or alternatively, microbial conversion, biotransformation, bioconversion, or enzymation [1,2]. 

Microbial enzymes can be applied as catalysts for chenucal synthesis in biosynthetic processes or in biotransformations (bioconversions). In a biosynthetic process the product is formed de novo by the microbial cell from substrates, such as monosaccharides, molasses, soytean and com steep liquor. In a biotransformation, however, a precursor that is usually chemically synthesised is converted in one or several enzyme catalysed steps into the desired chemical. This chemical may be die end product or may serve as a precursor for further chemical modification. 

Biotransformations, bioconversions impact on the whole range of biological, biotechnological and biomedical applications, such as in the analysis of genes and transcripts, the therapeutic treatment of abnormal molecules in diseases, the construction of specific enzymes and proteins for therapy, analysis, production, the assembly and construction of synthetic bio-synthetic pathways in organisms for the synthesis of intermediates, antibiotics, vitamins, enzymes, flavors. 

Figure 4.1 Comparison of metabolic bioconversions and enzymatic biotransformations...

Next to the metabolic bioconversions there are enzymatic biotransformations, which are characterized by a low number of fundamental well-defined reactions [11], However, there are often inherent limitations that need to be addressed the crucial ones are the following ... 

The procedure is very easy to reproduce and to scale up. Bioconversion products can be easily isolated by evaporation of the extraction solvent (e.g. tert-butyl methyl ether). Table 12.4 summarizes the product concentrations, molecular conversion yields and enantioselectivities obtained during linalool biotransformation with C. cassiicola DSM 62475. 

Johnson DV, Griengl H (1997) Abstract No P 1-52,3rd International Symposimn on Bio-catalysis and Biotransformations, 22-26 September, Le Grand Motte, Prance Club. Bioconversions en Synthese Organique, CNRS Marseille... 

Biocatalysis. Biocatalysis, also termed biotransformation and bioconversion, makes use of natural or modified isolated enzymes, enzyme extracts, or whole-cell systems for the production of small molecules. A starting material is converted by the biocatalyst in the desired product. Enzymes are differentiated from chemical catalysts particularly with regard to stereoselectivity. 

Biotransformation, also called microbial transformation or bioconversion, can be defined as a process dealing with the conversion of a compound, often called a precursor, into a structurally related compound(s) by a biocatalyst in a limited number of enzymatic steps. 

Inactivation of the biocatalyst owing to these effects can be a significant limitation for industrial application of enzymatic and whole-cell biotransformation. For more than 20 years, many attempts have been made to associate the toxicity of different solvents with some of their physicochemical properties and to explain the influence of the two-phase system composition on bioconversion efficiency. 

Another example of fungal bioconversion of linalool was described in literature the biotransformation by Diplodia gossypina ATCC 10936 [61]. A conversion scheme for the bioconversion of both (/ )-(-)- and (S)-(+)-linalool was proposed. 

In a recent extensive overview on the biotransformation of terpenoids by Aspergillus spp., Noma and Asakawa [92] also mentioned a sixth pathway of limonene bioconversion the hydroxylation at the C-4 position to give / -mentha-1,8-dien-4-ol (111), Fig. (20), a compound also identified earlier as one of the bioconversion metabolites of limonene with Penicillium italicum [83]. In this review, the fifth pathway, leading to isopiperitenol (113) which is further oxidised to isopiperitenone (112) and its rearrangement product, piperitenone (114) is also discussed. 

The biotransformation of (K)-(+)-pulegone was also studied by a Japanese group [116]. The major bioconversion metabolite of this substrate with Botrytis allii was (-)-(1 / )-8-hydroxy-4-p-menthen-3-one. The secondary major product from this biotransformation was isolated and its structure established as piperitenone [117]. It is interesting to note that the same group also investigated the bioconversion of piperitone, the dihydrogenation product of piperitenone a strain of Rhizoctonia solani was found able to hydroxylate the substrate preferentially at the 6-position [118,119]. 

Abraham et al. [144-146] studied the biotransformation of caryophyllene (190) and humulene (196) by Diplodia gossypina (ATCC 10936) and two strains of Chaetomium cochliodes (DSM 63353 and ATCC 10195), Fig. (38) and Fig. (39). Sixty three products, including 49 that had never been described previously, were obtained and tested for their biological activity [147]. More recently, the bioconversion of (-)-caryophyllene by Chaetomium cochliodes IFO 30576 was also studied by another group [148]. The substrate was first epoxidized at the C-C double bond, producing (-)-caryophyllene-4,5-oxide (191), which was then hydroxylated at the ge/n-dimethyl group and C-7 position giving 193. 

Recently, it has been demonstrated that the yeast Saccharomyces cerevisiae (DHW S-3) can also be used for the (R)-selective reduction of the acetylsilane rac-48. By analogy with the bioconversions illustrated in Scheme 10, incubation of rac-48 with resting free cells of this microorganism yielded a 1 1 mixture of the corresponding diastereomeric (1-hydroxyethyl)silanes (SiR,CR)-49 and (SiS,CR)-5057. Under preparative conditions, the biotransformation products were isolated in 43% yield (relative to rac-48). The enantiomeric purities of the silanes (SiR,CR)-49 and (SiS,CR)-50 were >98% ee. 

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