An industrial perspective fermentative bioreduction of aromatic ketones by Penicillium rubens VIT SS1 and Penicillium citrinum VIT SS2

Abstract

Microbial mediated, especially the fungi mediated asymmetric reduction of the ketone is one of the most promising tools for the synthesis of chiral alcohols. Many fungal cultures were isolated from soil and screened for the stereo selective bioreduction of acetophenone. The potential isolates are characterised using molecular techniques and found to be Penicillium rubens VIT SS1 (Genbank ID: MK063869) and Penicillium citrinum VIT SS2 (Genbank ID: MW960208). Both the isolates were tested for the bioreduction of few aromatic ketones such as 4-fluoro acetophenone, 3-hydroxy acetophenone, and oxcarbazepine, which are the key chiral intermediates of various pharmaceutical drugs. The P. rubens VIT SS1 produced (S)-alcohol obeying Prelog’s rule, and P. citrinum was anti-Prelog configuration in nature. Preparatory scale reactions were conducted using the optimised bioreduction process, and the keto loading was significantly increased by 12-fold (from 0.5 to 6 g/L) with >99% conversion and >98% enantiomeric excess. The study discloses the vast prospective approach of exploring filamentous fungi for sustainable synthesis of chiral alcohols in an environment-friendly, novel, and cost competent way.

Keywords:

• Bioreduction
• Penicillium sp
• aromatic ketone
• 3-hydroxy acetophenone
• licarbazepine

Acknowledgements

The authors want to express their gratitude 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. Also, we thank the management of IosynthLabs Private Limited, Bangalore, for their continuous encouragement.

Disclosure statement

The authors declare that they have no conflicts of interests.