Stereoselective Bioreduction of 1-(4-Methoxyphenyl)ethanone by Whole Cells of Marine-Derived Fungi

Souza

Appl Microbiol Biotechnol

et al. 2017

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.

Section: Discussionmentioning

confidence: 99%

Section: Distribution Of Ketone Reductases In Various Marine Fungimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Souza

Appl Microbiol Biotechnol

et al. 2017

“…Novel and robust microorganisms with perfect catalytic activity and stereoselectivity in the fields of biocatalytic reduction are in great demand. Future success can be achieved from the exploitation of marine microorganisms’ enzymatic potential [ 11 , 12 , 13 , 14 , 15 , 16 ]. 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 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

Marine-derived fungus Geotrichum candidum AS 2.361 was previously reported by our group as an active strain for the enantioselective reduction of ketones. Although some other Geotrichum strains were also found from the terrestrial sources, information on their stability and reusability is scarce. Herein, the stabilities—in terms of pH tolerance, thermostability, and storage stability, and reusability—of G. candidum AS 2.361 were described for the asymmetric reduction of a series of aromatic ketones. Two differently immobilized cells (agar immobilization and calcium alginate immobilization) as well as free cells were prepared. For three substrates (1-(3-bromophenyl) ethan-1-one (1b), 1-(2-chlorophenyl) ethan-1-one (1d), and acetophenone (1g)) immobilized cells on agar showed a great improvement in the bioreduction activities compared to the free cells, increasing yields up to 97% with ee values of 99%. Cells immobilized on agar/calcium alginate could maintain more than 90% of the original activities within the assayed pH ranges of 3.5–11, while free cells were highly sensitive to alkaline and acidic conditions. Concerning thermostability, immobilized cells on agar kept 99% of their original activities after incubation at 60 °C for 1 h, while almost no activity was detected for the free cells under the same condition. Immobilized cells were stable at 4 °C for 80 days without any activity loss, while free cells started to decrease the activity after storage at 4 °C for six days. The immobilized cells retained almost 99% activity after four reuse cycles, while free cells lost almost all the activities at on the third cycle.

“…Whole-cell based biocatalytic reduction has attracted great attention and has been extensively investigated in recent years for the unique advantages such as outstanding enantioselectivity, mild reaction conditions, environmental friendliness and regeneration of cofactors in situ [6-8]. So far, yeasts, bacteria, fungi, and even plant tissues have been extensively researched as biocatalysts for bio-reduction processes [9,10], and many excellent biocatalytic reaction processes have been developed. However, most of these biocatalysts follow Prelog’s rule [11], and thus the ( S )-alcohols are usually obtained when the smaller substituent of the ketone has the lower CIP priority.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic anti-Prelog reduction of prochiral ketones with whole cells of Acetobacter pasteurianus GIM1.158

Wei

Lou

et al. 2014

Microb Cell Fact

BackgroundEnantiomerically pure alcohols are important building blocks for production of chiral pharmaceuticals, flavors, agrochemicals and functional materials and appropriate whole-cell biocatalysts offer a highly enantioselective, minimally polluting route to these valuable compounds. At present, most of these biocatalysts follow Prelog’s rule, and thus the (S)-alcohols are usually obtained when the smaller substituent of the ketone has the lower CIP priority. Only a few anti-Prelog (R)-specific whole cell biocatalysts have been reported. In this paper, the biocatalytic anti-Prelog reduction of 2-octanone to (R)-2-octanol was successfully conducted with high enantioselectivity using whole cells of Acetobacter pasteurianus GIM1.158.ResultsCompared with other microorganisms investigated, Acetobacter pasteurianus GIM1.158 was shown to be more effective for the reduction reaction, affording much higher yield, product enantiomeric excess (e.e.) and initial reaction rate. The optimal temperature, buffer pH, co-substrate and its concentration, substrate concentration, cell concentration and shaking rate were 35°C, 5.0, 500 mmol/L isopropanol, 40 mmol/L, 25 mg/mL and 120 r/min, respectively. Under the optimized conditions, the maximum yield and the product e.e. were 89.5% and >99.9%, respectively, in 70 minutes. Compared with the best available data in aqueous system (yield of 55%), the yield of (R)-2-octanol was greatly increased. Additionally, the efficient whole-cell biocatalytic process was feasible on a 200-mL preparative scale and the chemical yield increased to 95.0% with the product e.e. being >99.9%. Moreover, Acetobacter pasteurianus GIM1.158 cells were proved to be capable of catalyzing the anti-Prelog bioreduction of other prochiral carbonyl compounds with high efficiency.ConclusionsVia an effective increase in the maximum yield and the product e.e. with Acetobacter pasteurianus GIM1.158 cells, these results open the way to use of whole cells of this microorganism for challenging enantioselective reduction reactions on laboratory and commercial scales.