Whole fungal elicitors boost paclitaxel biosynthesis induction in Corylus avellana cell culture

Abstract

Paclitaxel is an effective natural-source chemotherapeutic agent commonly applied to treat a vast range of cancers. In vitro Corylus avellana culture has been reported as a promising and inexpensive system for paclitaxel production. Fungal elicitors have been made known as the most efficient strategy for the biosynthesis induction of secondary metabolites in plant in vitro culture. In this research, C. avellana cell suspension culture (CSC) was exposed to cell extract (CE) and culture filtrate (CF) derived from Camarosporomyces flavigenus, either individually or combined treatment, in mid and late log phase. There is no report on the use of whole fungal elicitors (the combined treatment of CE and CF) for the elicitation of secondary metabolite biosynthesis in plant in vitro culture. The combined treatment of CE and CF significantly led to more paclitaxel biosynthesis and secretion than the individual use of them. Also, multivariate statistical approaches including stepwise regression (SR), ordinary least squares regression (OLSR), principal component regression (PCR) and partial least squares regression (PLSR) were used to model and predict paclitaxel biosynthesis and secretion. Based on value account for (VAF), root mean square error (RMSE), coefficient of determination (R 2), mean absolute percentage error (MAPE) and relative percent difference (RPD) can be concluded that mentioned regression models effectively worked only for modeling and predicting extracellular paclitaxel portion in C. avellana cell culture.

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

“…Previous studies (Salehi et al, 2019b;Salehi et al, 2019c;Farhadi et al, 2020;Salehi et al, 2020) demonstrated the positive influences of cell extract (CE) and culture filtrate (CF) of endophytic fungi on paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana. Fungal elicitor type, concentration and adding time, and also exposure time of cell culture (CSC harvesting time) should be optimized to achieve the maximum biosynthesis of paclitaxel in C. avellana CSC (Salehi et al, 2019b;Salehi et al, 2019c;Farhadi et al, 2020;Salehi et al, 2020). Precise analysis of the effects of these factors and their optimal selection would pave the way for the commercialization of bioprocessing C. avellana cells toward paclitaxel mass production.…”

“…In vitro culture of hazel ( Corylus avellana , European filbert) has been made known as a promising and inexpensive strategy for producing paclitaxel ( Gallego et al, 2017 ; Salehi et al, 2017 ; Salehi et al, 2018c ; Salehi et al, 2019b ; Salehi et al, 2019c ; Farhadi et al, 2020 ; Salehi et al, 2020 ). Biosynthesizing bioactive compounds in plants is influenced by various factors ( Torkamani et al, 2014 ; Salehi et al, 2017 ; Salehi et al, 2018a ; Salehi et al, 2018b ; Salehi et al, 2018c ; Salehi et al, 2019a ; Salehi et al, 2019b ; Salehi et al, 2019c ; Salehi et al, 2019d ).…”

“…Biosynthesizing bioactive compounds in plants is influenced by various factors ( Torkamani et al, 2014 ; Salehi et al, 2017 ; Salehi et al, 2018a ; Salehi et al, 2018b ; Salehi et al, 2018c ; Salehi et al, 2019a ; Salehi et al, 2019b ; Salehi et al, 2019c ; Salehi et al, 2019d ). Previous studies ( Salehi et al, 2019b ; Salehi et al, 2019c ; Farhadi et al, 2020 ; Salehi et al, 2020 ) demonstrated the positive influences of cell extract (CE) and culture filtrate (CF) of endophytic fungi on paclitaxel biosynthesis in cell suspension culture (CSC) of C. avellana . Fungal elicitor type, concentration and adding time, and also exposure time of cell culture (CSC harvesting time) should be optimized to achieve the maximum biosynthesis of paclitaxel in C. avellana CSC ( Salehi et al, 2019b ; Salehi et al, 2019c ; Farhadi et al, 2020 ; Salehi et al, 2020 ).…”

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

“…Nevertheless, Taxus recalcitrant behavior under in vitro culture is a drawback for fast-growing in vitro culture establishment of these valuable species [13]. Corylus avellana is a promising alternative for paclitaxel production because of its advantages including easy in vitro cultivation and fast-growing cells, and also extensive availability [13][14][15][16][17][18][19]. Large scale production of secondary metabolite (SM) through plant cell culture needs to apply several strategies including high-yielding cell line, growth medium optimization, precursor feeding, elicitation, etc.…”

“…Poor non-linear predictive and fitting abilities of traditional modeling methods [ 18 , 19 , 38 , 42 – 44 ] have shifted the studies to the use of data mining techniques such as artificial neural network (ANN) and neuro-fuzzy models. These models are able to identify and learn correlated patterns between input variables and corresponding target values in a complex and non-linear process.…”