Taguchi analysis and asymmetric keto-reduction of acetophenone and its derivatives by soil filamentous fungal isolate: Penicillium rubens VIT SS1

Abstract

Microbial asymmetric reduction of ketone is an efficient tool for the synthesis of chiral alcohols. This research focuses on exploring the soil fungal isolates for their ability toward the keto reduction of acetophenone and its derivatives to their corresponding chiral alcohols using growing cells. Bioreduction of acetophenone, 4-fluoro acetophenone, 4-methyl acetophenone, and 3-hydroxy acetophenone was carried out using different fungal cultures isolated from soil. Among the fungal isolates, Penicillium sp. and Aspergillus sp. showed significant bioconversion with varying enantio-selectivity. However, the Penicillium sp. has shown the maximum ability of bioreduction. The potential isolate was characterized using the internal transcribed spacer (ITS) region and found to be Penicillium rubens VIT SS1 (Genbank accession number: MK063869.1), which showed higher conversion and selectivity > 90%. The biocatalyst production and the reaction conditions were optimized using Taguchi analysis. The process conditions such as pH, temperature, media components, cosolvent, and substrate dosing were evaluated for the bioreduction of 3-hydroxy acetophenone, which is a key chiral intermediate of Phenylephrine and Rivastigmine using P. rubens VIT SS1. This study concludes about the potential of fungal cultures for sustainable synthesis of key chiral intermediates of Phenylephrine and Rivastigmine, similarly many aromatic chiral alcohols in simpler, novel, and cost-effective manner.

Keywords:

• Acetophenone
• Aspergillus sp.
• bioreduction
• 3-hydroxy acetophenone
• Penicillium sp.
• Rivastigmine

Acknowledgements

The authors thank to DST, honorable Chancellor, Dr. G. Viswanathan, Dr. Sekar Viswanathan, Mr. Sankar Viswanathan, and Mr. G.V. Selvam of VIT University for their constant encouragement and laboratory facilities from VIT University, Vellore, India to carry out this valuable work. The authors also thank the management of Iosynth Labs Private Limited, Bangalore for their support.

Disclosure statement

No potential conflict of interest was reported by the author(s).