Reprogramming plant specialized metabolism by manipulating protein kinases

Abstract

Being sessile, plants have evolved sophisticated mechanisms to balance between growth and defense to survive in the harsh environment. The transition from growth to defense is commonly achieved by factors, such as protein kinases (PKs) and transcription factors, that initiate signal transduction and regulate specialized metabolism. Plants produce an array of lineage-specific specialized metabolites for chemical defense and stress tolerance. Some of these molecules are also used by humans as drugs. However, many of these defense-responsive metabolites are toxic to plant cells and inhibitory to growth and development. Plants have, thus, evolved complex regulatory networks to balance the accumulation of the toxic metabolites. Perception of external stimuli is a vital part of the regulatory network. Protein kinase-mediated signaling activates a series of defense responses by phosphorylating the target proteins and translating the stimulus into downstream cellular signaling. As biosynthesis of specialized metabolites is triggered when plants perceive stimuli, a possible connection between PKs and specialized metabolism is well recognized. However, the roles of PKs in plant specialized metabolism have not received much attention until recently. Here, we summarize the recent advances in understanding PKs in plant specialized metabolism. We aim to highlight how the stimulatory signals are transduced, leading to the biosynthesis of corresponding metabolites. We discuss the post-translational regulation of specialized metabolism and provide insights into the mechanisms by which plants respond to the external signals. In addition, we propose possible strategies to increase the production of plant specialized metabolites in biotechnological applications using PKs.

Keywords: MAP kinase; Medicinal plants; Post-translational regulation; Protein kinases; Signal transduction; Specialized metabolites.

Fig. 1

A potential role of PKs in regulating specialized metabolism in medicinal plants. External stimuli are sensed by membrane-located kinases, such as wall-associated kinases (WAKs) and pathogen-associated molecular patterns (PAMPs) recognition receptor-like kinases (PRRs). The perception activates downstream kinases including cytosolic receptor-like kinases (RLCKs) and MAP kinase cascade, which eventually triggers the transcriptomic and metabolic reprogramming. PRRs may also connect with NADPH oxidases (RBOHs) or Ca²⁺-dependent kinases (CDPKs) to induce ROS/Ca²⁺-dependent signaling cascades, that may contribute to the regulation of specialized metabolism. TFs transcription factors; PM plasma membrane

Fig. 2

A strategy to screen for a transgenic plan that resists increased toxic metabolites. Modification of a kinase (1) in transgenic plants (2) by overexpressing or gene-editing (knock-in mutagenesis) an engineered kinase that is either constitutively activated (phospho-mimic) or with enhanced stability. “P” represents the phosphorylation of a protein kinase resulting in modified activity. The transgenic plants will be screened for increased metabolite accumulation and normal growth. In case the increase of metabolite accumulation causes growth inhibition, a secondary mutagenesis (3) using chemical means, such as ethyl methanesulfonate (EMS) or irradiation, will be employed to generate a mutant population (M1) with various growth phenotypes (plants with varying sizes in M2 population), from which a line (M3) with high metabolite accumulation and normal growth will be selected for futher breeding