Asymmetric reduction of electronically activated alkenes by ene reductases (ERs) is an attractive approach for the production of enantiopure chiral products. Herein, a novel FMN-binding ene reductase (PaER) from was heterologously expressed in BL21(DE3), and the recombinant enzyme was characterized for its biocatalytic properties. PaER displayed optimal activity at 40 °C and pH 7.5, respectively. The purified enzyme was quite stable below 30 °C over a broad pH range of 5.0-10.0. PaER was identified to have a good ability to reduce the C[double bond, length as m-dash]C bond of various α,β-unsaturated compounds in the presence of NADPH. In addition, PaER exhibited a high reduction rate ( = 3.57 s) and an excellent stereoselectivity (>99%) for ketoisophorone. Engineered cells harboring PaER and glucose dehydrogenase (for cofactor regeneration) were employed as biocatalysts for the asymmetric reduction of ketoisophorone. As a result, up to 1000 mM ketoisophorone was completely and enantioselectively converted to ()-levodione with a >99% ee value in a space-time yield of 460.7 g L d. This study provides a great potential biocatalyst for practical synthesis of ()-levodione.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9088392 | PMC |
http://dx.doi.org/10.1039/d2ra01716d | DOI Listing |
Molecules
December 2024
Institute of Chemistry, Moldova State University, 2028 Chisinau, Moldova.
The synthesis of tetra- and pentanorlabdane compounds with rearranged cycle B based on commercially available (+)-sclareolide is reported. Desired compounds were prepared from intermediate ketones via Baeyer-Villiger oxidation. The structures of synthesized compounds were confirmed by spectral IR, 1D (H, C, and DEPT), and 2D (H-COSY, H,C-HSQC, H,C-HMBC, H,N-HMBC, NOESY) NMR analyses, mass-spectrometry and single crystal X-rays diffraction.
View Article and Find Full Text PDFOrg Lett
December 2024
Process Research & Development, MRL, Merck & Co., Inc., Rahway, New Jersey 07065, United States.
We report the remote stereocontrol of all-carbon quaternary γ-centers via an ene-reductase (ERED)-catalyzed desymmetrization of prochiral cyclohexadienones. By leveraging high-throughput experimentation (HTE) protocols, we were able to rapidly identify EREDs capable of desymmetrizing both spirocyclic cyclohexadienones and non-spirocyclic 2,6-disubstituted cyclohexadienone substrates in up to 85% yield with excellent levels of stereoselectivity (up to >99% ee and >20:1 dr) under mild reaction conditions.
View Article and Find Full Text PDFBiochemistry
January 2025
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.
Dithiolopyrrolone (DTP) natural products are broad-spectrum antimicrobial and anticancer prodrugs. The DTP structure contains a unique bicyclic ene-disulfide that once reduced in the cell, chelates metal ions and disrupts metal homeostasis. In this work we investigate the intracellular activation of the DTPs and their resistance mechanisms in bacteria.
View Article and Find Full Text PDFBioorg Chem
January 2025
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, China. Electronic address:
Secondary biotransformation of 11β-hydroxy-dianabol (11β,17β-dihydroxy-17α-methylandrost-1,4-dien-3-one) (1), catalyzed by using two fungi Gibberella fujikuroi and Cunninghamella blakesleeana at ambient conditions, was carried out to synthesize its analogues. Transformation of compound 1 with G. fujikuroi yielded a new metabolite, 11β, 17β-dihydroxy-17α-methyl-5β-androst-1-ene-3-one (2), while four new derivatives, 6β, 17β-dihydroxy-17α-methylandrost-1,4-diene-3,11-dione (3), 15α,17β-dihydroxy-17α-methylandrost-1,4-diene-3,11-dione (4), 6β,11β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (5), and 7β,11β,17β-trihydroxy-17α-methylandrost-1,4-dien-3-one (6) were obtained by transformation with C.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
November 2024
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), ChemBioMed Interdisciplinary Research Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!