Asymmetric Biocatalysis

The first generation process developed for the production of L-carnitine was a single-stage continuous process with cell-recycling that utilized the maintenance phase production that is characteristic of this strain. This process had a very high volumetric productivity of 130 g/L/d in the steady state [3], Owing to the kinetics of this process the product solution contained 92% L-carnitine and 8% unconverted butyrobetaine. L-Carnitine and butyrobetaine have very similar physio-chemical properties, which makes their separation from the product solution diffi- 

The environmental considerations for the biotechnological process are also important. A comparison of the waste stream (Fig. 2) from the bio-process with that from the Lonza chemical synthesis [5] showed that the amount of waste water, total organic carbon (TOC), salts, and waste for incineration were all considerably lower for the bio-process [6], 

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Wohlgemuth, R. (2010) Asymmetric biocatalysis with microbial enzymes and cells. Curr. Opin. Microbiol., 13, 283-292. 

The oxidation of heteroatoms and, in particular, the conversion of sulfides to asymmetric sulfoxides has continued to be a highly active field in biocatalysis. In particular, the diverse biotransformations at sulfur have received the majority of attention in the area of enzyme-mediated heteroatom oxidation. This is particularly due to the versatile applicability of sulfoxides as chiral auxiliaries in a variety of transformations coupled with facile protocols for the ultimate removal [187]. 

Itoh, N., Nakamura, M., Inoue, K. and Makino, Y. (2007) Continuous production of chiral 1,3-butanediol using immobilized biocatalysts in a packed bed reactor promising biocatalysis method with an asymmetric hydrogen-transfer bioreduction. Applied Microbiology and Biotechnology, 75 (6), 1249-1256. 

The best results for the asymmetric cyanohydrination reactions are obtained through biocatalysis, using the readily available enzyme oxynitrilase. This provides cyanohydrins from a number of substances with over 98% ee.146... 

A detailed review of the literature of non-enzymic catalysts is given in Comprehensive Asymmetric Catalysis eds Jacobsen, E.N., Pfaltz, A. and Yamamoto, H. Springer-Verlag, Berlin/Heidelberg, 1999. As an introductory text for post-graduate students see Catalysis in Asymmetric Synthesis, Williams, J.MJ. Sheffield Academic Press, Sheffield, UK, 1999. A comparison of biocatalysis versus chemical catalysis has also been made by Averill, B.A., Laane, N.W.M., Straathof, A.JJ. and Tramper, J., in Catalysis An Integrated Approach (eds van Santen, R.A. van Leeuwen, P.W.N.M., Moulijn, J.A. and Averill, B.A.) Elsevier, The Netherlands, 1999, Chapter 7. 

Biocatalysis is still an emerging field hence, some transformations are more established than others.Panke et alP have performed a survey of patent applications in the area of biocatalysis granted between the years 2000 and 2004. They found that although hydrolases, which perform hydrolyses and esterifications, still command widespread attention and remain the most utilized class of enzyme (Figure 1.5), significant focus has turned towards the use of biocatalysts with different activities and in particular alcohol dehydrogenases (ADHs) - also known as ketoreductases (KREDs) - used for asymmetric ketone reduction. 

Microbial reduction has been recognized for decades as a laboratory method of preparing alcohols from ketones with exquisite enantioselectivity. The baker s yeast system represents one of the better known examples of biocatalysis, taught on many undergraduate chemistry courses. Numerous other microorganisms also produce the ADH enzymes (KREDs) responsible for asymmetric ketone reduction, and so suitable biocatalysts have traditionally been identified by extensive microbial screening. Homann et have... 

Keywords Peroxidase, Biocatalysis, Asymmetric synthesis. Kinetic resolution. Hydroperoxide, Epoxidation, Sulfoxidation, Halogenation, Hydroxylation, Phenol coupling. 

Amino acids may be produced by biocatalysis either by asymmetric synthesis or... 

As discussed in part 2.2.3 biocatalysis may be used both in asymmetric synthesis and resolution in order to obtain enantiopure compounds. A major difference between asymmetric synthesis and resolution is that the former in theory may give 100% yield of the wanted enantiomer. Resolution on the other hand can only give 50% yield since the starting point is a mixture of 50% of each enantiomer. This is the classical disadvantage of resolution. 

In Chapter 2, the two methods of enantioselective biocatalysis have been introduced Asymmetric synthesis and kinetic resolution. 

Turnover numbers (TONs) and substrate/catalyst ratios ([S]/[C] ratios) seem the preferred quantities in homogeneous catalysis, in contrast to biocatalyst loading (units L-1) and TTNs in biocatalysis. In the case of slow homogeneous chemical catalysts, the [S]/[C] ratio can approach unity (stoichiometric conditions). In the limit of no recycle, the values for TTN and TON are identical upon re-use of catalyst, TTN increases correspondingly. Whereas recycling is very important in biocatalysis, it does not seem to be common practice in homogeneous chemical asymmetric catalysis. 

Matsuda T, Yamanaka R et al (2009) Recent progress in biocatalysis for asymmetric oxidation and reduction. Tetrahedron Asymmetry 20 513-557... 

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