Identification of a newly isolated Rhodotorula mucilaginosa NQ1 and its development for the synthesis of bulky carbonyl compounds by whole‐cell bioreduction

Abstract

A strain NQ1, which showed efficient asymmetric reduction of 3,5‐bis(trifluoromethyl) acetophenone (BTAP) to enantiopure (S)‐[3,5‐bis(trifluoromethyl)phenyl]ethanol ((S)‐BTPE), which is the key intermediate for the synthesis of a receptor antagonist and antidepressant, was isolated from a soil sample. Based on its morphological and internal transcribed spacer sequence, the strain NQ1 was identified to be Rhodotorula mucilaginosa NQ1. Some key reaction parameters involved in the bioreduction catalyzed by whole cells of R. mucilaginosa NQ1 were subsequently optimized, and the optimized conditions for the synthesis of (S)‐BTPE were determined to be as follows: 5·0 ml phosphate buffer (200 mmol l−1, pH 7·0), 80 mmol l−1 of BTAP, 250 g (wet weight) l−1 of resting cell, 35 g l−1 of glucose and a reaction for 18 h at 30°C and 180 rev min−1. The strain NQ1 exhibited a best yield of 99% and an excellent enantiomeric excess of 99% for the preparation of (S)‐BTPE under the above optimal conditions, and could also asymmetrically reduce a variety of bulky prochiral carbonyl compounds to their corresponding optical hydroxyl compound with excellent enantioselectivity. These results indicated that R. mucilaginosa NQ1 had a good capacity to reduce BTAP to its corresponding (S)‐BTPE, and might be a new potential biocatalyst for the production of valuable chiral hydroxyl compounds in industry.

Microbial alcohol dehydrogenases: recent developments and applications in asymmetric synthesis

“…In addition to the bacterial strains mentioned above, 37 Wang et al reported a fungal strain, Rhodotorula mucilaginosa NQ1, isolated from soil for the reduction of 3,5-bis(trifluoromethyl)acetophenone ( 4 ) to ( S )-[3,5-bis(trifluoromethyl)-phenyl]ethanol ( 5 ) (Scheme 6). 58 After systematic optimization studies, 80 mmol L −1 of substrate 4 was reduced using 250 g (wet weight) per L of resting cells and 35 g L −1 of glucose as the cosubstrate, which led to product 5 in good isolated yield (82%) and ee (99%). In addition, reduction of substrate 4 using whole cells of strain NQ1 was scaled up with 1 L of reaction mixture in a 5 L bioreactor.…”

Biocatalytic Asymmetric Synthesis of (S)‐1‐[3,5‐bis(trifluoromethyl)phenyl]ethanol by an Immobilized KRED in Batch and Flow Conditions

“…Several microorganisms have been reported in recent years, such as Cyberlindnera saturnus, [25] Sphingomonas sp., [26] Candida tropicalis, [27] Rhodotorula mucilaginosa, [28] Rhodococcus erytropolis, [29] Saccharomyces rhodotorula. [30] Medium engineering and in particular the use of deep eutectic solvents (DESs) was explored in some of these studies [25,27a,29] to overcome the problem of unsatisfactory results with whole cell biocatalysis.…”