With the breakthroughs in enzyme/protein engineering and new insights into the structure-function studies, enzymes and microorganisms have been extensively employed as a unique tool to facilitate the process of drug discovery and development. The major virtues of biotransformation, in terms of mild reaction conditions, high regio- or stereoselectivity, effective catalysis and process greenness, have attracted the attention of the scientists from both academia and industry. China, as a growing power in economy and science, has emphasized the redirection of future economic growth by eliminating environmental concerns, and Chinese scientists have made significant impacts in the area of biotransformation, similar to other scientific disciplines, in recent years. The special issue of Current Organic Chemistry concerning biotransformation in drug discovery and development includes five reviews on a number of key topics in this area currently under development, which is contributed by the leading scientists in this area in China.
The first review is provided by Prof. Yu. With the advances of chemical genetics and high-throughput screening platforms, lead compounds from natural sources have become increasingly valuable for interrogating fundamental aspects of biological systems. This review focuses on important microbial transformations used for the generation of lead compounds with pharmaceutical utilities and further structural diversification of complex natural products, especially those from traditional Chinese Medicines, such as terpenoids, alkaloids and steroids.
Studies on the biosynthesis of natural products contribute to the renaissance of natural products as drug discovery and development. Nevertheless, several factors hindered this demand, including rediscovery of known natural products with high frequency and the technical challenges associated with purification and structural elucidation of novel compounds from natural sources. Prof. Shang describes the biosynthesis of polyketides and non-ribosomal peptides and addresses the gene manipulation, chemo-enzymatic applications, structure prediction and innovative strategies developed in recent years to explore the vast portion of natural-product structural diversity that remains unexploited for their applications.
Dehydrogenases/reductases have been utilized as valuable biocatalysts to synthesize chiral alcohols for a relatively long period of time, but these enzymes have continued to play vital roles in biotransformation and the number of enzymes and industrial applications is remarkably growing. The third review by myself covers the recent development of a number of new dehydrogenases/reductases with useful substrate specificity, stereoselectivity and regioselectivity. It also provides an overview of the recent advances in the application of dehydrogenases/reductase to synthesize chiral building blocks for pharmaceuticals, including different therapeutic agents for various diseases.
Recent trends of biocatalyst engineering and solvent engineering in non-aqueous biocatalysis are covered in the contribution by Prof. Xu. This review presents exhaustively collected examples of enzyme catalyzed reactions in aqueous-organic media. As compared to non-aqueous biocatalysis in conventional organic solvents, enzyme has emerged as an imperative tool on the enhancements of catalytic activity, stability and selectivity in addition to the utilization of ionic liquids in the reaction media.
The discovery and construction of new biocatalysts with desired substrate specificity and stability used in green chemistry and pharmaceuticals have long been pursued by biologists and chemists. The last review contributed by Prof. Feng focuses on the advancements of molecular redesign and construction of new biocatalysts by rational and irrational strategies from three aspects: improvement of the catalytic performance, optimization of the substrate specificity and de novo design of biocatalysts.
Finally, it has been a pleasure for me to serve as the Guest Editor of this special issue at Current Organic Chemistry. I would like to thank all of the authors contributing to this special issue for their valuable time. It would not be possible to have such a fine issue with a number of profound reviews from the collective efforts by these outstanding scientists. I am sure that their contributions will provide extremely useful information and future directions on the research in the area of biotransformation.