The Development of Biocatalysis as a Tool for Drug Discovery

Abstract

Enzymes are versatile biocatalysts capable of performing selective reactions. The advantages of enzymes in comparison to classical chemistry including chemical catalysts are the generally milder process conditions and avoidance of harmful reactants. Their high selectivity and specificity are especially beneficial for the enzymatic synthesis of new products with potential applications in drug research. Therefore, in the past decades, the utilization of isolated enzymes or whole-cell biocatalysts has spread through a growing number of biotechnological industries. The applications comprise the production of chiral building blocks for the pharmaceutical and fine chemical industry, the enzymatic synthesis of drug metabolites for testing of toxicity, function, biological activity, degradation and the production of biocatalytically modified natural products, which all play a role in drug discovery. Especially Oreste Ghisalba's contributions, which paved the way for the industrial use of enzymes, will be considered in this review.

Bioengineering of Anti‐Inflammatory Natural Products

“…A well‐known method to increase the structural diversity from an isolated natural product is whole‐cell biotransformation. The molecule of interest is fed to an organism other than the producer (in most cases a fungus or a bacterium), which then carries out various site‐specific and stereospecific reactions (Figure 2A) [18,19] . Although the outcome of such a derivatization is often not foreseeable, the knowledge about microbial strains carrying out desirable transformations has accumulated over the years.…”

“…The molecule of interest is fed to an organism other than the producer (in most cases a fungus or a bacterium), which then carries out various site-specific and stereospecific reactions (Figure 2A). [18,19] Although the outcome of such a derivatization is often not foreseeable, the knowledge about microbial strains carrying out desirable transformations has accumulated over the years. Quite often, proven "biotransformers" are easily available from microbial culture collections.…”

A Bio-logical Approach to Catalysis in the Pharmaceutical Industry

“…[35] These three aspects (synthesis of chiral building blocks, metabolism investigation and late stage functionalisation) are thoroughly covered in a review by Schwarz et al, which is published in this issue of Chimia. [36] Instead, this review looks at how the ability of enzymes to conduct delicate chemistry in aqueous media can benefit the drug discovery process, focusing on examples in peptide drug discovery and DNA encoded chemical libraries, which will be described in the next paragraphs.…”

Utilization of Soybean Oil Waste for a High-Level Production of Ceramide by a Novel Phospholipase C as an Environmentally Friendly Process

“…Most importantly, they usually produce toxic byproducts, which make the obtained materials unsuitable for food applications. Instead, the biosynthesis of ceramide via enzymatic strategy is an alternative method that is efficient, sustainable, and easy to achieve industrial-scale production . Previously, a feasible bioprocess has been established to synthesize ceramide from sphingomyelin (SM) via the enzymatic hydrolysis, showing advantages of cost-efficient, green, and security compared with the extraction and chemical synthesis …”

“…Instead, the biosynthesis of ceramide via enzymatic strategy is an alternative method that is efficient, sustainable, and easy to achieve industrial-scale production. 8 Previously, a feasible bioprocess has been established to synthesize ceramide from sphingomyelin (SM) via the enzymatic hydrolysis, showing advantages of cost-efficient, green, and security compared with the extraction and chemical synthesis. 9 SM is an important phospholipid composed of ceramide and polar headgroup phosphorylcholine, which is similar to the structure of glycerophospholipid.…”