Dr. Santosh Kumar Padhi, and his Ph.D. student Ayon Chatterjee, Department of Biochemistry, in collaboration with Dr. N. Prakash Prabhu and his Ph.D. student G. Priyanka, School of Life Sciences has recently published in ACS Catalysis, 2024, 14, 12623-12634 (doi.org/10.1021/acscatal.4c04000.) entitled “Uncovering Hydroxynitrile Lyase Variants with Promiscuous Diastereoselective Nitroaldolase Activity Towards Highly Stereocontrolled Synthesis of Anti β-Nitroalcohols.” ACS Catalysis is a prestigious journal of American Chemical Society with an impact factor of 11.3.
Sustainable manufacture of fine chemicals, chiral molecules and active pharmaceutical ingredients is a not only the demand of chemical and pharma industries but also a global desire. Optically active β-nitroalcohol diastereomers and their derivatives are found as key structural motifs in natural products, and bioactive molecules. While their synthesis using diastereoselective Henry reaction (DHR) is well-known, it is majorly achieved using chemical catalysts. Biocatalysis offer sustainable technology along with high selectivity and efficiency to the synthesis of diverse chemical structural units. The authors used enzyme engineering and prepared variants of Arabidopsis thaliana hydroxynitrile lyase (AtHNL) which empowered the promiscuous DHR with not only broad synthetic scope toward different aldehydes, and nitroalkane, but also high enantio- and diastereoselectivity (up to >99% enantiomeric excess, >99% diastereomeric excess, >99% isomeric content, and ~3470 total turnover number) in the production of diverse anti (1R,2S)-β-nitroalcohols.
The tailor-made biocatalyst could be used in gram-scale biocatalysis followed by a one-step chemical synthesis to prepare L-norephedrine, a therapeutic, with >99% enantiomeric excess and diastereomeric excess. Mechanistic study using isotope label experiments and computations studied uncovered the molecular basis of the stereocontrol displayed by the biocatalyst. This study has been patent filed (Application No: 202341031596) from University of Hyderabad. Dr. Padhi believes that this technology will find industrial application.