Taguchi analysis and asymmetric keto-reduction of acetophenone and its
derivatives by soil filamentous fungal isolate: Penicillium rubens VIT SS1
Saravanan Jothia,b and Suneetha Vuppua
aSchool of Biosciences and Technology, VIT University, Vellore, India; bR&D, Iosynth Labs Private Limited, Bangalore, India
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 enantioselectivity.
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.