%0 Journal Article %T Enhancement of isoprene production in engineered Synechococcus elongatus UTEX 2973 by metabolic pathway inhibition and machine learning-based optimization strategy. %A Yadav I %A Rautela A %A Gangwar A %A Wagadre L %A Rawat S %A Kumar S %J Bioresour Technol %V 387 %N 0 %D 2023 Nov 12 %M 37579861 %F 11.889 %R 10.1016/j.biortech.2023.129677 %X An engineered Synechococcus elongatus UTEX 2973-IspS.IDI is used to enhance isoprene production through geranyl diphosphate synthase (CrtE) inhibition and process parameters (light intensity, NaHCO3 and growth temperature) optimization approach. A cumulative isoprene production of 1.21 mg/gDCW was achieved with productivity of 12.6 μg/gDCW/h in culture supplemented with 20 μg/mL alendronate. This inhibition strategy improvises the cumulative isoprene production 5.76-fold in presence of alendronate. The maximum cumulative production of isoprene is observed to be 5.22 and 6.20 mg/gDCW (54.4 and 64.6 μg/gDCW/h) at statistical and artificial neural network genetic algorithm (ANN-GA) optimized conditions, respectively. The overall increase of isoprene production is found to be 29.52-fold using an integrated approach of inhibition and ANN-GA optimization in comparison to unoptimized cultures without alendronate. This study reveals that alendronate use as a potential inhibitor and machine learning based optimization is a better approach in comparison to statistical optimization to enhance the isoprene production.