Asymmetric synthesis of (S)-3-chloro-1-phenyl-1-propanol using Saccharomyces cerevisiae reductase with high enantioselectivity

Applied Microbiology and Biotechnology
Yun Hee ChoiHyung-Kwoun Kim

Abstract

3-Chloro-1-phenyl-1-propanol is used as a chiral intermediate in the synthesis of antidepressant drugs. Various microbial reductases were expressed in Escherichia coli, and their activities toward 3-chloro-1-phenyl-1-propanone were evaluated. The yeast reductase YOL151W (GenBank locus tag) exhibited the highest level of activity and exclusively generated the (S)-alcohol. Recombinant YOL151W was purified by Ni-nitrilotriacetic acid (Ni-NTA) and desalting column chromatography. It displayed an optimal temperature and pH of 40 degrees C and 7.5-8.0, respectively. The glucose dehydrogenase coupling reaction was introduced as an NADPH regeneration system. NaOH solution was occasionally added to maintain the reaction solution pH within the range of 7.0-7.5. By using this reaction system, the substrate (30 mM) could be completely converted to the (S)-alcohol product with an enantiomeric excess value of 100%. A homology model of YOL151W was constructed based on the structure of Sporobolomyces salmonicolor carbonyl reductase (Protein Data Bank ID: 1Y1P). A docking model of YOL151W with NADPH and 3-chloro-1-phenyl-1-propanone was then constructed, which showed that the cofactor and substrate bound tightly to the active site of the enzyme...Continue Reading

References

Mar 5, 1992·Nature·R LüthyD Eisenberg
Dec 5, 1993·Journal of Molecular Biology·A Sali, T L Blundell
Jan 29, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Meera VaswaniSubramanyam Ramesh
Apr 30, 2004·Journal of Computational Chemistry·Junmei WangDavid A Case
Dec 31, 2004·The Journal of Organic Chemistry·Iwona A KaluznaJon D Stewart
Jun 28, 2005·Nucleic Acids Research·Johannes SödingAndrei N Lupas
Jun 28, 2005·Nucleic Acids Research·Joost SchymkowitzLuis Serrano
Aug 9, 2005·Applied and Environmental Microbiology·Yoshihide MakinoNobuya Itoh
Oct 4, 2005·Journal of Computational Chemistry·David A CaseRobert J Woods
Jan 18, 2006·Journal of Biotechnology·Holger PfruenderDirk Weuster-Botz
Feb 3, 2007·Journal of Computational Chemistry·Ruth HueyDavid S Goodsell
Sep 11, 2007·Journal of Biotechnology·Kirsten SchroerStephan Lütz
Dec 7, 2007·Accounts of Chemical Research·Jeffrey C MoorePaul N Devine
Jul 12, 2008·Gene·Bingding Huang, Michael Schroeder
Mar 14, 2009·Bioorganic & Medicinal Chemistry Letters·Mark AndrewsMalcolm MacKenny

❮ Previous
Next ❯

Citations

Jul 8, 2010·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Klaus BreichaKarsten Niefind
Oct 31, 2020·Frontiers in Bioengineering and Biotechnology·Jee Loon FooMatthew Wook Chang

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.