Model-based fed-batch cultivation ofViola odorataplant cells exhibiting antimalarial and anticancer activity

Abstract Viola odorata is used in the indigenous medicine to treat respiratory tract disorders and is limited in availability. Bioprocess principles can be applied to develop sustainable methods to produce high-quality V. odorata biomass. To this effect, a modified stirred tank reactor and a balloon-type bubble column reactor were used to improve biomass production. Nutrient feeding strategies were developed using first principle-based mathematical modelling to achieve higher cell density in the reactor. Experimental validation of the fed-batch model-predicted strategy resulted in a two-fold enhancement in biomass production (32.2 g DW L-1) at the bioreactor level. Also, bioreactor-cultivated biomass extracts were tested for in vitro hemolytic, cytotoxic, anti-inflammatory, and in vivo antiplasmodial activities. This is the first report on fed-batch cultivation in bioreactors and the antiplasmodial activity of V. odorata. Overall, the bioactive potential of the in vitro-generated biomass extracts is found to be similar to that in the natural plant biomass extracts. Highlights Cultivation of V. odorata cell suspension culture using a modified stirred tank and balloon-type bubble column bioreactors. Batch kinetic models were developed and extrapolated into a fed-batch model. Enhanced biomass production (32.2 g DW L-1) in bioreactors using a nutrient-feeding strategy. Extracts showed anti-inflammatory effects and up to 80 % inhibition of parasite growth, with no hemolytic activity. Confirmed antiplasmodial activity in vivo, effective alongside artesunate. In vitro-generated biomass extracts showed comparable bioactive potential to that of natural plants. Competing Interest Statement The authors have declared no competing interest. Footnotes The names, affiliations and e-mail addresses of co-authors are listed below: Babu Ra, Email: biotechbabu92{at}gmail.com, Manokaran Veeramanib, Email: manokaran.deva{at}gmail.com, Aadinath Wallepurea, Email: aadhinathw{at}gmail.com, Vignesh Muthuvijayana, Email: vigneshm{at}iitm.ac.in a Department of Biotechnology, Bhupat and Jyoti Mehta School of Biosciences, Indian Institute of Technology Madras, Chennai, 600 036, India b Department of Chemical Engineering, Indian Institute of Technology Madras, Chennai, 600 036, India