34583-34-1Relevant articles and documents
Borneol dehydrogenase from Pseudomonas sp. TCU-HL1 possesses novel quinuclidinone reductase activities
Chen, Hao-Ping,Ho, Tsung-Jung,Hung, Chien-Chi,Khine, Aye Aye,Lu, Pei-Chieh,Simaremare, Sailent Rizki Sari,Tung, Chi-Hua,Wu, Jia-Ru,Yiin, Lin-Ming
, (2021/08/30)
Borneol dehydrogenase (BDH) catalyses the last step of the camphor biosynthetic pathway in plants and the first reaction in the borneol degradation pathway in soil microorganisms. Native or engineered BDH can be used to produce optically pure borneol and camphor. The recently reported apo-form crystal structure of BDH (PDB ID: 6M5N) from Pseudomonas sp. TCU-HL1 superimposes well with that of 3-quinuclidinone reductase (QR) (PDB ID: 3AK4) from Agrobacterium tumefaciens. QR catalyses the conversion of 3-quinuclidinone into (R)-3-(?)-quinuclidinol, an important chiral synthone for several drugs. However, the kinetic parameter, kcat, of QR was not determined in the previous reports even though both BDH and QR have various potential industrial applications. Here, we aimed to further characterise their structural and functional relationship. Recombinant QR with the native sequence was cloned, expressed in E. coli, and purified. We found that 3-quinuclidinone can be used as an alternative substrate for BDH. Only (R)-3-(?)-quinuclidinol was detected in this BDH-catalysed reaction. The results of 3 D molecular docking simulation show that 3-quinuclidinone and (+)-/(-)- borneol were docked to two different parts of the QR active site. In contrast, all three compounds are docked uniformly to the alpha-1 helix of BDH. There results explain why BDH can turnover 3-quinuclidinone, while QR can not act on (+)-/(-)-borneol.
Microbial stereospecific reduction of 3-quinuclidinone with newly isolated Nocardia sp. and Rhodococcus erythropolis
Wang, Yu,Li, Jianjiong,Wu, Qiaqing,Zhu, Dunming
, p. 14 - 19 (2013/08/24)
Two bacterium strains, Nocardia sp. WY1202 and Rhodococcus erythropolis WY1406, were isolated from soil samples. They catalyzed the asymmetric reduction of 3-quinuclidinone to give enantiomeric pure (R)- and (S)-3-quinuclidinol, respectively. The optimal temperatures for the bioreduction by Nocardia sp. and R. erythropolis were 30 °C and 37 °C, respectively, while both strains showed highest activity at pH 8.0. Without external addition of expensive NADH or NADPH, (R)-3-quinuclidinol and (S)-3-quinuclidinol were obtained with 93% and 92% isolated yield and >99% enantiomeric excess. As such, microbial reduction by Nocardia sp. WY1202 or R. erythropolis WY1406 offers a new stereospecific approach to both antipodes of 3-quinuclidinol of pharmaceutical importance.
Industrially viable preparation of (R)-3-Quinuclidinol, a key building block of muscarine M1, M3 agonists and M3 antagonists
Chavakula, Ramadas,Mutyala, Narayana Rao,Chennupati, Srinivasa Rao
, p. 507 - 509 (2013/12/04)
-