Modulation of fatty acid metabolism and tricarboxylic acid cycle to enhance the lipstatin production through medium engineering in Streptomyces toxytricini

This work investigated the potential of medium engineering to obtain maximum biomass, non-conventional carbon sources for lipstatin production and modulation of tricarboxylic acid (TCA) cycle to promote lipstatin synthesis. It was found that 2:3 carbon and nitrogen ratio, produced maximum biomass of 7.9 g/L in growth medium and 6.6 g/L in pre-seed medium. Among the studied non-conventional carbon sources i.e., soya flour 40 g/L and sesame oil 30 mL/L were found producing 1109.37 mg/L (1.24-fold of control) and 1196.75 mg/L (1.34-fold of control) lipstatin respectively. Supplementation of TCA cycle intermediates revealed that NADH and succinic acid showed lipstatin production to 1132.99 mg/L and 1171.10 mg/L respectively. Experimental outcome was validated in 7 L bioreactor and produced 2242.63 mg/L lipstatin which was ∼14% higher than shake flask.