Broadening the Scope of Biocatalysis in Sustainable Organic Synthesis

Abstract

This Review is aimed at synthetic organic chemists who may be familiar with organometallic catalysis but have no experience with biocatalysis, and seeks to provide an answer to the perennial question: if it is so attractive, why wasn't it extensively used in the past? The development of biocatalysis in industrial organic synthesis is traced from the middle of the last century. Advances in molecular biology in the last two decades, in particular genome sequencing, gene synthesis and directed evolution of proteins, have enabled remarkable improvements in scope and substantially reduced biocatalyst development times and cost contributions. Additionally, improvements in biocatalyst recovery and reuse have been facilitated by developments in enzyme immobilization technologies. Biocatalysis has become eminently competitive with chemocatalysis and the biocatalytic production of important pharmaceutical intermediates, such as enantiopure alcohols and amines, has become mainstream organic synthesis. The synthetic space of biocatalysis has significantly expanded and is currently being extended even further to include new‐to‐nature biocatalytic reactions.

The 15th Frank Warren Organic Chemistry Conference

“…Roger Sheldon, detailed the genesis of green chemistry,a nd its integration into mainstream manufacturing, through the development of biocatalytic engineering. [6] In as imilar vein, Prof. Rosalyn Klein discussed case studies emanating from her lab on the application of green chemistry principles in the medicinal chemistry context,w hileP rof. Moira Bode (University of the Witwatersrand), described her group's recent advances in biocatalysis for the kinetic resolution of enantiopureM orita-Baylis-Hillman Adducts.…”

Thermal and Mechanical Stability of Immobilized Candida antarctica Lipase B: an Approximation to Mechanochemical Energetics in Enzyme Catalysis.

“…Enzymes are potent biocatalysts that are able to carry out numerous chemical transformations with remarkable chemo‐, regio‐ and stereo‐selectivity . The intrinsic sustainability of enzymatic processes along with the use of green reaction conditions such as absence of potentially toxic solvents, and activation with non‐conventional sources of energy has expanded the use of biocatalysis in both chemical industries and in academic institutions, focusing in drug discovery and in the synthesis of molecules with relevant biological activity .…”

“…Enzymes are potent biocatalysts that are able to carry out numerous chemical transformations with remarkable chemo-, regio-and stereo-selectivity. [1][2][3][4][5] The intrinsic sustainability of enzymatic processes along with the use of green reaction conditions such as absence of potentially toxic solvents, and activation with non-conventional sources of energy has expanded the use of biocatalysis in both chemical industries and in academic institutions, focusing in drug discovery and in the synthesis of molecules with relevant biological activity. [6][7][8] Recent developments in protein engineering and enzyme directed evolution, [9,10] together with the availability of efficient methods for the production of recombinant molecules, have led to rapidly expanding new fields in biocatalysis.…”

Re‐Investigation of Hydration Potential of Rhodococcus Whole‐Cell Biocatalysts towards Michael Acceptors

“…Their unique 3‐dimensional structures provide ways to activate the water molecule as well as stabilise transition states during the reaction . Therefore, using microbial activities or applying purified enzymes in biocatalytic reactions to achieve a selective water addition to double bonds is nowadays often seen as advantageous . Hydratases (EC 4.2.1.x) catalyse the water addition to activated as well as isolated double bonds.…”

“…[1,4] Therefore, using microbial activities or applying purified enzymes in biocatalytic reactions to achieve a selective water addition to double bonds is nowadays often seen as advantageous. [5][6][7] Hydratases (EC 4.2.1.x) catalyse the water addition to activated as well as isolated double bonds. However, especially enzymes from the primary metabolism exhibit a narrow substrate scope which confines the applicability of these enzymes to their natural substrates.…”