Modeling of paclitaxel biosynthesis elicitation in Corylus avellana cell culture using adaptive neuro-fuzzy inference system-genetic algorithm (ANFIS-GA) and multiple regression methods

Abstract

Paclitaxel as a microtubule-stabilizing agent is widely used for the treatment of a vast range of cancers. Corylus avellana cell suspension culture (CSC) is a promising strategy for paclitaxel production. Elicitation of paclitaxel biosynthesis pathway is a key approach for improving its production in cell culture. However, optimization of this process is time-consuming and costly. Modeling of paclitaxel elicitation process can be helpful to predict the optimal condition for its high production in cell culture. The objective of this study was modeling and forecasting paclitaxel biosynthesis in C. avellana cell culture responding cell extract (CE), culture filtrate (CF) and cell wall (CW) derived from endophytic fungus, either individually or combined treatment with methyl-β-cyclodextrin (MBCD), based on four input variables including concentration levels of fungal elicitors and MBCD, elicitor adding day and CSC harvesting time, using adaptive neuro-fuzzy inference system (ANFIS) and multiple regression methods. The results displayed a higher accuracy of ANFIS models (0.94-0.97) as compared to regression models (0.16-0.54). The great accordance between the predicted and observed values of paclitaxel biosynthesis for both training and testing subsets support excellent performance of developed ANFIS models. Optimization process of developed ANFIS models with genetic algorithm (GA) showed that optimal MBCD (47.65 mM) and CW (2.77% (v/v)) concentration levels, elicitor adding day (16) and CSC harvesting time (139 h and 41 min after elicitation) can lead to highest paclitaxel biosynthesis (427.92 μg l-1). The validation experiment showed that ANFIS-GA method can be a promising tool for selecting the optimal conditions for maximum paclitaxel biosynthesis, as a case study.

A hybrid model based on general regression neural network and fruit fly optimization algorithm for forecasting and optimizing paclitaxel biosynthesis in Corylus avellana cell culture

“…As shown in Table 1 , the statistical values for GRNN-FOA models displayed higher prediction accuracy than regression models in previous study [ 12 ]. This finding was in line with the previous studies [ 7 , 13 ] showing AI technology had the superior performances as compared to conventional modeling methods for forecasting growth and paclitaxel biosynthesis in C. avellana cell culture.…”

“…In vitro culture of hazel (Corylus avellana) has been named as a promising and low-cost strategy for paclitaxel production [5][6][7][8][9][10][11][12][13]. The advantages of paclitaxel production through C. avellana cell culture are that the establishment of its in vitro culture is more straightforward than that of Taxus [6][7][8][9][10][11][12], and also the response of hazel to genetic manipulation through Agrobacterium is likely more hopeful as compared to that of Taxus since C. avellana is a dicotyledonous plant [14]. Obtaining highproducing cell cultures is essential for producing secondary metabolites by way of plant in vitro culture [15].…”

“…Obtaining highproducing cell cultures is essential for producing secondary metabolites by way of plant in vitro culture [15]. Biosynthesizing bioactive compounds in plants are influenced by various factors [6][7][8][16][17][18][19]. Fungal elicitors including cell extract (CE) and culture filtrate (CF) have been described as an impressive strategy for improving paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana [6,7,[10][11][12][13].…”

“…Biosynthesizing bioactive compounds in plants are influenced by various factors [6][7][8][16][17][18][19]. Fungal elicitors including cell extract (CE) and culture filtrate (CF) have been described as an impressive strategy for improving paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana [6,7,[10][11][12][13]. Fungal elicitor type, concentration level and adding time as well as exposure time of cell culture to it (harvesting time) should be optimized to achieve the highest biosynthesis of paclitaxel in C. avellana CSC [6,7,[10][11][12][13].…”

“…Fungal elicitors including cell extract (CE) and culture filtrate (CF) have been described as an impressive strategy for improving paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana [6,7,[10][11][12][13]. Fungal elicitor type, concentration level and adding time as well as exposure time of cell culture to it (harvesting time) should be optimized to achieve the highest biosynthesis of paclitaxel in C. avellana CSC [6,7,[10][11][12][13]. Precise analysis of the effects of these factors and their optimal selection would be a step forward to commercialize the bioprocess of C. avellana cells for paclitaxel mass production.…”