Multistep biocatalysis

Hydroxy-Stearic acid (from OA) O2 Multistep biocatalysis 48 (22) >... 

Multistep biocatalysis for the preparation of optically pure epoxides was applied by Sello and coworkers [24, 25]. The commercially available 3-vinyl benzaldehyde was the substrate of choice for the synthesis of 3-(oxiran-2-yl) benzoic acid in high yields and optical purity by solely employing enzyme catalysis (Scheme 3.6). This goal was achieved by applying a mixed culture approach with different recombinant E. coli strains expressing, individually, both oxidizing biocatalysts. One strain contained a native ADH and a SMO from Pseudomonas Jiuorescens ST, while a second one expressed a naphthalene dihydrodiol dehydrogenase (NDDH) from P. Jiuorescens N3. 

Schrewe, M., Ladkau, N., Buehler, B., and Schmid, A. (2013) Direct terminal alkylamino-functionalization via multistep biocatalysis in one recombinant whole-cell catalyst. Adv. Synth. Catal., 355, 1693-1697. 

B. Buhler, B. Witholt, B. Hauer, A. Schmid, Characterization and application of xylene monooxygenase for multistep biocatalysis, Appl. Environ. Microbiol. 68 (2002) 560-568. 

Production of fine chemicals and active pharmaceutical ingredients (APIs) will also continue to benefit from the judicious application of biocatalysis, in many cases as part of multistep synthetic schemes. Of particular relevance is the increasing demand for chirally pure pharmaceuticals, driven by concerns about the unwanted side-effects often associated with racemic drugs. Another growth area is likely to be the production of biologically active carbohydrates, traditionally requiring complex and expensive chemistries for production, to be used as pharmaceuticals, in infant formula, and as nutritional supplements. 

Whole-cell based biocatalysis utilizes an entire microorganism for the production of the desired product. One of the oldest examples for industrial applications of whole-cell biocatalysis is the production of acetic acid from ethanol with an immobilized Acetobacter strain, which was developed nearly 200 yr ago. The key advantage of whole-cell biocatalysis is the ability to use cheap and abundant raw materials and catalyze multistep reactions. Recent advances in metabolic engineering have brought a renaissance to whole-cell biocatalysis. In the following sections, two novel industrial processes that utilize whole-cell biocatalysis are discussed with emphasis on the important role played by metabolic engineering. 

In Chapter 1 (Section 1.6.1, Bio-based Economy) it was noted how white biotechnologies contribute to sustainability. We may cite, as an additional example, that DSM s route to the antibiotic cephalexin (a combination of a fermentation and an enzymatic reaction with respect to multistep chemo-synthesis) reduces of 65% the materials and energy used, and about 50% the variable costs [153]. Other examples of biocatalysis and white biotechnologies used industrially by DSM are summarized in Table 2.5. 

Presumably, coordination catalysis and biocatalysis will be more intercrmnected in the very near future, and we can imagine for the multistep synthesis of an elaborated product the successive intervention of both these strategies. This volume would be helpful to academic and industrial researchers who are involved in the fields of coordination chemistry, homogeneous catalysis, and organic synthesis, in order to develop efficient tools to have the access to fine chemicals from abundant and low-cost substrates. 

By 1930, biocatalysis was also integrated into multistep chemical syntheses. The manufacture of o-ephedrine was based on Neuberg s demonstration that yeast would convert benzaldehyde to phenylacetyl-carbinol [(R)-l-phenyl-l-hydroxypropan-2-one (11)] (Neuberg and Ohle, 1922). Of particular interest, because of its relation with the work of Brown and Bertrand, is the synthesis of vitamin C [L-ascorbic acid (12)]. Two... 

Basic concept of cascade biocatalysis, (a) Conventional multistep chemical synthesis of compound A-F, via intermediates B-E. (b) Replacement of steps B-C and D-E by biocataly-sls, maintaining Interstep recovery. (c) Replacement of adjacent steps B-C, C-D, D-E by biocatalysis, with the potential for eliminating interstep recovery. 

Biocatalysis for drug discovery and development with an industrial perspective, and biocatytic cascade reactions with e integration of biocatalysts with one or more additional reaction steps, and multistep biocatalytic reaction sequences and multienzyme-catalyzed conversions, are presented. 

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