Green (cell) factories for advanced production of plant secondary metabolites

Abstract

For centuries plants have been intensively utilized as reliable sources of food, flavoring, agrochemical and pharmaceutical ingredients. However, plant natural habitats are being rapidly lost due to climate change and agriculture. Plant biotechnology offers a sustainable method for the bioproduction of plant secondary metabolites using plant in vitro systems. The unique structural features of plant-derived secondary metabolites, such as their safety profile, multi-target spectrum and "metabolite likeness," have led to the establishment of many plant-derived drugs, comprising approximately a quarter of all drugs approved by the Food and Drug Administration and/or European Medicinal Agency. However, there are still many challenges to overcome to enhance the production of these metabolites from plant in vitro systems and establish a sustainable large-scale biotechnological process. These challenges are due to the peculiarities of plant cell metabolism, the complexity of plant secondary metabolite pathways, and the correct selection of bioreactor systems and bioprocess optimization. In this review, we present an integrated overview of the possible avenues for enhancing the biosynthesis of high-value marketable molecules produced by plant in vitro systems. These include metabolic engineering and CRISPR/Cas9 technology for the regulation of plant metabolism through overexpression/repression of single or multiple structural genes or transcriptional factors. The use of NMR-based metabolomics for monitoring metabolite concentrations and additionally as a tool to study the dynamics of plant cell metabolism and nutritional management is discussed here. Different types of bioreactor systems, their modification and optimal process parameters for the labor industrial-scale production of plant secondary metabolites are specified.

From Ethnomedicine to Plant Biotechnology and Machine Learning: The Valorization of the Medicinal Plant Bryophyllum sp.

“…Currently, medicinal plants represent the source of more than 25% of drugs officially approved by the Food and Drug Administration (FDA) and the European Medicinal Agency (EMA) for the development of novel synthetic drugs [128]. Their derived by-products account for the 75-90% of the total used in the primary healthcare systems of economically developed nations [129].…”

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

“…On the other hand, the extraction of NPs from intact plant limit the commercial production of these compounds owing to low yield, environmental restrictions and extinction risk of these valuable pharmaceutical sources [9,10]. Therefore, using biotechnological approaches particularly plant cell culture named "green cell factories" is a promising bioproduction platform to overcome these limitations and produce plant NPs on a large scale [1,9,11].…”

“…On the other hand, our previous researches [9,15,27] indicated the positive influences of different elicitors derived from endophytic fungi, cell extract (CE), culture filtrate (CF) and cell wall (CW), on paclitaxel biosynthesis in C. avellana cell culture. Several factors including elicitor concentration level, cell culture age and elicitor exposure time affect the process of paclitaxel biosynthesis elicitation in C. avellana cell culture [5,11,21], and optimal selection of these factors is a determinative issue for maximum biosynthesis of this valuable SM. Nevertheless, optimization of elicitation process is time-consuming and costly.…”

“…Several factors including elicitor concentration level, cell culture age and elicitor exposure time affect the process of paclitaxel biosynthesis elicitation in C . avellana cell culture [ 5 , 11 , 21 ], and optimal selection of these factors is a determinative issue for maximum biosynthesis of this valuable SM. Nevertheless, optimization of elicitation process is time-consuming and costly.…”

Analysis of plant secondary metabolism using stable isotope‐labelled precursors

“…It also provides information on the regulation of these metabolic pathways, in particular when in vitro and also in vivo measurements are integrated. In particular, NMR in vivo has demonstrated its potential for direct characterisation of the physiological and metabolic state of living cells in a non‐invasive manner and an ability to track metabolic changes in response to development and changes in the environment 48 . This approach is all the more capable of providing information on the regulation of a metabolic pathway, metabolic bottlenecks, concurrent pathways, etc., when using perturbated biological systems such as mutants, transgenic lines or elicited cells.…”