Mathematical Modeling of Growth and Paclitaxel Biosynthesis in Corylus avellana Cell Culture Responding to Fungal Elicitors Using Multilayer Perceptron-Genetic Algorithm

Paclitaxel is the top-selling anticancer medicine in the world. In vitro culture of Corylus avellana has been made known as a promising and inexpensive strategy for producing paclitaxel. Fungal elicitors have been named as the most efficient strategy for enhancing the biosynthesis of secondary metabolites in plant cell culture. In this study, endophytic fungal strain HEF₁₇ was isolated from C. avellana and identified as Camarosporomyces flavigenus. C. avellana cell suspension culture (CSC) elicited with cell extract (CE) and culture filtrate (CF) derived from strain HEF₁₇, either individually or combined treatment, in mid and late log phase was processed for modeling and optimizing growth and paclitaxel biosynthesis regarding CE and CF concentration levels, elicitor adding day, and CSC harvesting time using multilayer perceptron-genetic algorithm (MLP-GA). The results displayed higher accuracy of MLP-GA models (0.89-0.95) than regression models (0.56-0.85). The great accordance between the predicted and observed values of output variables (dry weight, intracellular, extracellular and total yield of paclitaxel, and also extracellular paclitaxel portion) for both training and testing subsets supported the excellent performance of developed MLP-GA models. MLP-GA method presented a promising tool for selecting the optimal conditions for maximum paclitaxel biosynthesis. An Excel^® estimator, HCC-paclitaxel, was designed based on MLP-GA model as an easy-to-use tool for predicting paclitaxel biosynthesis in C. avellana CSC responding to fungal elicitors.

Keywords: artificial neural network; cell extract; culture filtrate; endophytic fungus; secondary metabolite.