Fine chemicals biocatalysis

The term biotransformation or biocatalysis is used for processes in which a starting material (precursor) is converted into the desired product in just one step. This can be done by use either of whole cells or of (partially) purified enzymes. Product examples range from bulk chemicals (such as acrylamide) to fine chemicals and chiral synthons (chiral amines or alcohols, for example). There are several books and reviews dealing with the use of bio transformations either at laboratory or at industrial scales [1, 10-13]. 

Given the wide utility of biocatalysis in the fine chemical industry, why is there such an in-house reliance on classical methods of enantioseparation In fact, why is biocatalysis not applied more generally as a replacement for atom-inefficient or hazardous reactions that are intensively used in the pharmaceutical industry, such as amidation, reduction and oxidation ... 

Biocatalysis contributes significantly to the generation of APIs through the supply of chiral building blocks from the fine chemical industry. In contrast, there is a clear underutilization within the pharmaceutical industry, where it could provide more efficient and greener methods of late-stage intermediate and API production. 

Panke, S., Held, M. and Wubbolts, M., Trends and innovations in industrial biocatalysis for the production of fine chemicals. Curr. Opin. Biotechnol., 2004,15, 272-279. 

The perspectives for an increasing use of biotechnology processes (biocatalysis, microbial fermentation) for LMW fine chemicals are promising. Substitution of traditional chemicals by biotechnology processes constitutes the most important means for reduction of manufacturing cost for existing fine chemicals. By 2010,30-60% of fine-chemical production processes are expected to comprise a biotechnology step ... 

In conclusion, biocatalysis should be, or become, part of the technology toolbox of any fine-chemical company. Cell culture fermentation, on the other hand, should be considered only by large fine-chemical companies with a full war chest and a long-term strategic orientation. 

Catalysis is becoming important and, in the future, biocatalysis (using cells, cell debris, enzymes) may be the most efficient way of producing fine chemicals. 

A. Eiese and M. V. Filho, Production of fine chemicals using biocatalysis, Curr. Opin. Biotechnol. 1999, 10, 595-603. 

Roberts, S. M. Biocatalysis for fine Chemical Synthesis (Wiley, Weinheim, 1999). 

The major application of cross-linked enzyme crystals in the pharmaceutical and fine chemicals industry is in biocatalysis or the use of CLCs to catalyze various... 

Most fine chemical syntheses involve multiple steps including protection, catalysis, and deprotection operations. In those cases where exquisite enantio- or regioselectivity or specificity is demanded, then biocatalysis will be considered. The mild conditions often used for biocatalysis confer the added advantage of overcoming the need for protection and deprotection in many cases.4 Nevertheless, the enzymatic process will usually be one or at best a few steps, in an otherwise 10-20-step synthesis. Consequently, biocatalytic reactions are most normally preceded and followed by a chemical conversion. With this in mind, implementation needs to consider the integration of the biocatalytic step with the neighboring operations. 

The use of industrial enzymes for the synthesis of bulk and fine chemicals represents a somewhat specialized application for biocatalysts relative to their broader uses, as outlined above. Industrial biocatalysis is, however, becoming increasingly relevant within the chemical industry for the production of a wide range of materials (see Table 31.3).1,2,4-8 Broadly defined, a biocatalytic process involves the acceleration of a chemical reaction by a biologically derived catalyst. In practice, the biocatalysts concerned are invariably enzymes and are used in a variety of forms. These include whole cell preparations, crude protein extracts, enzyme mixtures, and highly purified enzymes, both soluble and immobilized. 

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. 

Biocatalysis has many advantages in the context of green chemistry, e.g. mild reaction conditions and often fewer steps than conventional chemical procedures because protection and deprotection of functional groups are often not required. Consequently, classical chemical procedures are increasingly being replaced by cleaner biocatalytic alternatives in the fine chemicals industry (see later). 

The potential environmental and economic advantages that biocatalysts promise certainly warrant the necessary investments required to overcome the energy barriers of reducing biocatalysis to practice in the synthesis of both commodity and fine chemicals. The last quarter-century has brought extensive advancement is the field of biocatalysis and the next quarter-century promises to yield further advances. 

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