A Comparative Study on Asymmetric Reduction of Ketones Using the Growing and Resting Cells of Marine-Derived Fungi

Abstract

Whole-cell biocatalysts offer a highly enantioselective, minimally polluting route to optically active alcohols. Currently, most of the whole-cell catalytic performance involves resting cells rather than growing cell biotransformation, which is one-step process that benefits from the simultaneous growth and biotransformation, eliminating the need for catalysts preparation. In this paper, asymmetric reduction of 14 aromatic ketones to the corresponding enantiomerically pure alcohols was successfully conducted using the growing and resting cells of marine-derived fungi under optimized conditions. Good yields and excellent enantioselectivities were achieved with both methods. Although substrate inhibition might be a limiting factor for growing cell biotransformation, the selected strain can still completely convert 10-mM substrates into the desired products. The resting cell biotransformation showed a capacity to be recycled nine times without a significant decrease in the activity. This is the first study to perform asymmetric reduction of ketones by one-step growing cell biotransformation.

Microbial Oxidoreductases: Biotechnological and Synthetic Applications

“…However, in many reactions, dif iculties remain in achieving suficient purity and productivity (Musa and Phillips, 2011). To overcome this disadvantage of conventional processes, the biological catalysts, ie enzymes, are used for the asymmetrical synthesis of optically pure substances (Liu, 2018).…”

Enzymatic synthesis of enantiopure alcohols: current state and perspectives

“…48 For example, marine-derived fungi have been successfully used for the asymmetric reduction of a series of aromatic ketones in our laboratory. 2 Novel industrially relevant ketoreductases continue to become available, and novel process engineering concepts have been developed. For example, an attractive approach has been developed using an engineered ketoreductase, which allows the bioreduction of the ketoreductases in the synthesis of atorvastatin and atazanavir, Fig.…”

“…Currently, enantiomerically pure alcohols are important building blocks that are widely used as intermediates in the chemical and pharmaceutical industries for synthesis of ne products with chiral centers such as, avourings, agrochemicals, drugs, liquid crystals and specialty materials. 1,2 Thus, their synthesis is continuously of great interest to researchers. Considering that the traditional synthetic methods predominantly use toxic metals or expensive complex ligands, enzyme-catalysed syntheses offer signicant advantages to these methods, such as remarkable chemo-, regio-, and stereoselectivity, environmentally benign processes and energyefficient operations.…”

Immobilized and Free Cells of Geotrichum candidum for Asymmetric Reduction of Ketones: Stability and Recyclability

“…Marine microorganisms are thoroughly adapted to surviving and growing under extreme environments, resulting in their production of novel enzymes with optimal biochemical properties at harsh conditions (extreme temperature, pressure, pH, or organic solvent) [ 17 , 18 ]. Such habitat-related characteristics make marine microorganisms ideal biocatalysts of asymmetric bioreduction for the production of the desired enantiomerically pure alcohols [ 19 , 20 , 21 ].…”

“…In our previous work [ 19 , 20 , 21 ], 13 marine-derived fungus strains were characterized as active strains for the catalytic activity in the enantioselective reduction of 13 aromatic ketones of different compound classes. Excellent-to-good yields and enantioselectivities were achieved with these marine-derived fungi, such as Rhodotorula mucilaginosa , R. rubra , Penicillium citrinum , Aspergillus sydowii , A. sclerotiorum , and G. candidum AS 2.361.…”