The use of marine-derived fungi for preparation of enantiomerically pure alcohols

Abstract

A highly enantioselective and minimally polluting approach to optically pure chiral alcohols is developed using cheap, readily available and sustainable marine-derived fungi as catalysts. An evaluation of the synthetic potential of 13 Chinese marine fungi was performed to screen for enantioselective reduction of 13 aromatic ketones from different compound classes as substrates. Good yields and excellent enantioselectivities were achieved with this method. In details, first the effects of several crucial variables on the bioreduction of aromatic ketones with whole cells of marine fungi were explored systematically. Next, we obtained insight into the substrate scope of the tested fungi under the optimized conditions, and selected reduction processes were performed at a commercial scale of up to 1000 mL to determine scalability, which led to excellent yields and enantioselectivities. Last, ketone reductases from two prioritized fungi exhibited good recyclability, with those of Rhodotorula mucilageinosa giving a > 95% yield with up to 99% ee during 3 cycles and those of Rhodotorula rubra giving a > 95% yield with up to 99% ee during 9 cycles.

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

“…To compare the biocatalytic activity of free and immobilized G. candidum AS 2.361 cells for the asymmetric reduction of ketones, both free cells and immobilized cells (on agar and calcium alginate) were used as catalysts for the reactions. Free cells were obtained as described previously [ 19 ]. Immobilized cells were obtained according to the protocols described in the Experimental Section 3.2 .…”

“…Organic solvents were removed using a rotary evaporator. Free cells of G. candidum AS 2.361 were obtained as described in a previous report by our group [ 19 ]. Geotrichum candidum AS 2.361 used in this study was deposited and commercially available in Guangdong Culture Collection Center ( ), which belongs to the World Federation for Culture Collections (Budapest Notification no.…”

“…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.…”

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

“…Indeed, fungi host novel enzymes showing optimal activities at extreme values of salt concentrations, pH and temperature, compared to enzymes isolated from terrestrial origins [ 51 , 52 , 53 ]. These advantages, in addition to their chemical and stereochemical properties and readily available sources (e.g., sea sources of enzymes represented by microorganisms or fungi, plants or animals; ease of growth), make marine enzymes ideal biocatalysts for fine chemistry and pharmaceutical sectors; these enzymes should be broadly explored [ 28 , 29 , 30 , 48 , 54 , 55 , 56 ].…”