Biocatalytic drawbacks

Supercritical fluids (SCFs) and in particular supercritical carbon dioxide (scC02) have also been shown to provide a unique medium in which to perform biocatalytic transformations. The ability to perform biocatalysis in a supercritical fluid was first demonstrated in 1985 by several groups. There are several advantages to the use of SCFs, as well as some drawbacks that need to be addressed if large-scale processes are to be developed. 

It can be concluded from the various results described above that numerous continuous efforts have been devoted to the synthesis of enantiopure epoxides over the last twenty to thirty years which has led to important fundamental knowledge on this topic. Unfortunately, many of these approaches still suffer from severe limitations as far as large-scale (industrial) applications are concerned. This is particularly the case for direct epoxidation of alkenes using monooxygenases. Indeed, most of these biocatalytic routes imply multienzy-matic processes, and/or are hampered by substrate and/or product inhibition leading to low productivity. Highly sophisticated processes had therefore to be set up in order to partially overcome these drawbacks. 

Enzymes have many potential advantages when used as catalysts for chemical synthesis. The unique properties offered by these biocatalysts are, first of all, their often outstanding chemo-, regio-, and, in particular, stereoselectivity. Furthermore, enzymes are highly efEcient catalysts working under very mild conditions. However, enzymes do also have some drawbacks that may limit their potential use, such as ability to accept a limited substrate pool only, and a moderate operational stability. Ways of overcoming most of these potential limitations exist and they pose in most cases more of a perceived than a real problem. Well over 100 different biocatalytic processes have been implemented on an industrial scale [1]. A few processes are... 

The heterologous expression of metabolically related enzymes represents one way to overcome several of the limitations and drawbacks of the above-described mixed culture strategies. Within a biocatalytic context, such an approach is appeahng only when all enzymes involved display sufHdently broad substrate tolerance in order to ultimately form a system capable of converting various starting materials. 

Although Leloir-GTs are accepted as perfect candidates for the biocatalytic production of glycans their dependence on nucleotide sugars makes cost effective synthesis strategies more complex. One approach to overcome this drawback is the (re)generation of donor-substrates with multienzyme systems [24,... 

Despite the previously mentioned examples vhich clearly prove the synthetic value of BY, there are several drawbacks that limit its vhdespread application to preparative organic chemistry (i) very low substrate concentrations tolerated by the microorganism that lead to an intrinsically too low productivity (ii) difficult work-up, due to the troublesome separation of the product from a huge amount of biomass (iii) typically incomplete conversion and occurrence of side reactions that imply the use of industrially unappealing chromatographic steps (iv) presence of enzymes with the same specific biocatalytic activity that might have different enantioselectivity. 

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