Jasmonates are phytohormones that regulate many aspects of plant growth, development, and defense. Within the signaling cascades that are triggered by jasmonates, the JASMONATE-ZIM DOMAIN (JAZ) ...repressor proteins play a central role. The endogenous bioactive JA-lle conjugate mediates the binding of JAZ proteins to the F-box protein CORONATINE INSENSITIVE1 (COM), part of the Skpi/Cullin/F-box SCF COI1 ubiquitin E3 ligase complex. Upon the subsequent destruction of the JAZ proteins by the 26S proteasome, multiple transcription factors are relieved from JAZ-mediated repression, allowing them to activate their respective downstream responses. However, many questions remain regarding the targets, specificity, function, and regulation of the different JAZ proteins. Here, we review recent studies on the model plant Arabidopsis thaliana that provided essential and novel insights. JAZ proteins have been demonstrated to interact with a broad array of transcription factors that each control specific downstream processes. Recruitment of the corepressor TOPLESS unveiled a mechanism for JAZ-mediated gene repression. Finally, the presence of JAZ proteins was also found to be regulated by alternative splicing and interactions with proteins from other hormonal signaling pathways. Overall, these contemporary findings underscore the value of protein-protein interaction studies to acquire fundamental insight into molecular signaling pathways.
Plants produce countless specialized compounds of diverse chemical nature and biological activities. Their biosynthesis often exclusively occurs either in response to environmental stresses or is ...limited to dedicated anatomical structures. In both scenarios, regulation of biosynthesis appears to be mainly controlled at the transcriptional level, which is generally dependent on a combined interplay of DNA-related mechanisms and the activity of transcription factors that may act in a combinatorial manner. How environmental and developmental cues are integrated into a coordinated cell type-specific stress response has only partially been unraveled so far. Building on the available examples from (metabolic) gene expression, here we propose theoretical models of how this integration of signals may occur at the level of transcriptional control.
An increasing number of publications highlight the importance of cell type-specific stress responses that seem to be predominantly controlled at the transcriptional level. This may also be the case for JA-mediated defense mechanisms, but which components of combinatorial control of gene expression are involved in this is unclear.
The number of described interactions of TFs of the same or different families is rising.
An increasing number of tools has become available, facilitating the research on nonmodel plants such as next-generation sequencing, genome editing, and the isolation of populations of specific cell types.
Past research in the field of regulation of specialized metabolism has focused on the discovery of TFs regulating specific metabolic pathway genes. The ensuing findings provide an excellent starting point to unravel how different TFs act in a coordinated manner and how DNA-related mechanisms have an impact on gene expression in specialized metabolism.
Over the years, jasmonates (JAs) have become recognized as one of the main plant hormones that regulate stress responses by activating defense programs and the production of specialized metabolites. ...High JA levels have been associated with reduced plant growth, supposedly as a result of the reallocation of carbon sources from primary growth to the biosynthesis of defense compounds. Recent advances suggest however that tight regulatory networks integrate several sensing pathways to steer plant metabolism, and thereby drive the trade-off between growth and defense. In this review, we discuss how JA influences primary metabolism and how it is connected to light-regulated processes, nutrient sensing and energy metabolism. Finally, we speculate that JA, in a conceptual parallelism with adrenaline for humans, overall boosts cellular processes to keep up with an increased metabolic demand during harsh times.
•Jasmonate boosts defense and metabolic processes to increase plant resilience.•Jasmonate is linked to light-regulated processes, HY5 activity, and photomorphogenesis.•Jasmonate connects with the central energy sensor TOR and the SnRK complex.•Like adrenaline in animals, jasmonate boosts plant performances but overexposure can be harmful.
Jasmonates (JAs) act as conserved elicitors of plant secondary metabolism. JA perception triggers extensive transcriptional reprogramming leading to the concerted activation of entire metabolic ...pathways. This observation inspired numerous quests for ‘master’ regulators capable of enhancing the production of specific sets of valuable plant metabolites. Many transcription factors (TFs), often JA-activated themselves, with a role in the JA-modulated regulation of metabolism were discovered. At the same time, it became clear that metabolic reprogramming is subject to complex control mechanisms integrated in robust cellular networks. In this review, we discuss current knowledge of the effect of JA-modulated TFs in the elicitation of secondary metabolism in the model plant Arabidopsis (Arabidopsis thaliana) and a range of medicinal plant species with structurally divergent secondary metabolites. We draw parallels with the regulation of secondary metabolism in fungi and consider the remaining challenges to map and exploit the transcriptional machineries that drive JA-mediated elicitation of plant secondary metabolism.
Abscisic acid (ABA) is a sesquiterpene signaling molecule produced in all kingdoms of life. To date, the best known functions of ABA are derived from its role as a major phytohormone in plant abiotic ...stress resistance. Different organisms have developed different biosynthesis and signal transduction pathways related to ABA. Despite this, there are also intriguing common themes where ABA often suppresses host immune responses and is utilized by pathogens as an effector molecule. ABA also seems to play an important role in compatible mutualistic interactions such as mycorrhiza and rhizosphere bacteria with plants, and possibly also the animal gut microbiome. The frequent use of ABA in inter-species communication could be a possible reason for the wide distribution and re-invention of ABA as a signaling molecule in different organisms. In humans and animal models, it has been shown that ABA treatment or nutrient-derived ABA is beneficial in inflammatory diseases like colitis and type 2 diabetes, which confer potential to ABA as an interesting nutraceutical or pharmacognostic drug. The anti-inflammatory activity, cellular metabolic reprogramming, and other beneficial physiological and psychological effects of ABA treatment in humans and animal models has sparked an interest in this molecule and its signaling pathway as a novel pharmacological target. In contrast to plants, however, very little is known about the ABA biosynthesis and signaling in other organisms. Genes, tools and knowledge about ABA from plant sciences and studies of phytopathogenic fungi might benefit biomedical studies on the physiological role of endogenously generated ABA in humans.
Terpenoids constitute a large and diverse class of natural products that serve many functions in nature. Most of the tens of thousands of the discovered terpenoids are synthesized by plants, where ...they function as primary metabolites involved in growth and development, or as secondary metabolites that optimize the interaction between the plant and its environment. Several plant terpenoids are economically important molecules that serve many applications as pharmaceuticals, pesticides, etc. Major challenges for the commercialization of plant-derived terpenoids include their low production levels in planta and the continuous demand of industry for novel molecules withnewor superior biological activities. Here, wehighlight several synthetic biology methods to enhance and diversify the production of plant terpenoids, with a foresight towards triterpenoid engineering, the least engineered class of bioactive terpenoids. Increased or cheaper production of valuable triterpenoids may be obtained by ‘classic’ metabolic engineering of plants or by heterologous production of the compounds in other plants or microbes. Novel triterpenoid structures can be generated through combinatorial biosynthesis or directed enzyme evolution approaches. In its ultimate form, synthetic biology may lead to the production of large amounts of plant triterpenoids in in vitro systems or custom-designed artificial biological systems.
Saponins are a structurally diverse family of triterpenes that are widely found as main constituents in many traditional plant-based medicines and often have bioactivities of industrial interest. The ...heterologous production of triterpene saponins in microbes remains challenging and only limited successful pathway engineering endeavors have been reported. To improve the production capacities of a Saccharomyces cerevisiae saponin production platform, we assessed the effects of several hitherto unexplored gene knockout targets on the heterologous production of triterpenoids. Here, we show that the disruption of the phosphatidic acid phosphatase-encoding PAH1 through CRISPR/Cas9 results in a dramatic expansion of the endoplasmic reticulum (ER), which stimulated the production of recombinant triterpene biosynthesis enzymes and ultimately boosted triterpenoid and triterpene saponin accumulation. Compared to the wild-type starter strain, accumulation of the oleanane-type sapogenin β-amyrin, of its oxidized derivative medicagenic acid, and its glucosylated version medicagenic-28-O-glucoside was respectively increased by eight-, six- and 16-fold in the pah1 strain. A positive effect of pah1 could also be observed for the production of other terpenoids depending on ER-associated enzymes for their biosynthesis, such as the sesquiterpenoid artemisinic acid, which increased by twofold relative to the wild-type strain. Hence, this report demonstrates that pathway engineering in yeast through transforming the subcellular morphology rather than altering metabolic fluxes is a powerful strategy to increase yields of bioactive plant-derived products in heterologous hosts.
•A powerful strategy for engineering yeast-based metabolite production is proposed.•The principle relies on the transformation of subcellular morphology.•Expansion of the endoplasmic reticulum (ER) increases yeast metabolic capacity.•Expanded ER structures can harbour higher plant ER-associated enzyme levels.•The principle is applicable to plant-derived triterpenoids and sesquiterpenoids.
Summary
With tens of thousands of characterized members, terpenoids constitute the largest class of natural compounds that are synthesized by all living organisms. Several terpenoids play primary ...roles in the maintenance of cell membrane fluidity, as pigments or as phytohormones, but most of them function as specialized metabolites that are involved in plant resistance to herbivores or plant–environment interactions. Terpenoids are an essential component of human nutrition, and many are economically important pharmaceuticals, aromatics and potential next‐generation biofuels. Because of the often low abundance in their natural source, as well as the demand for novel terpenoid structures with new or improved bioactivities, terpenoid biosynthesis has become a prime target for metabolic engineering and synthetic biology projects. In this review we focus on the creation of new‐to‐nature or tailor‐made plant‐derived terpenoids in photosynthetic organisms, in particular by means of combinatorial biosynthesis and the activation of silent metabolism. We reflect on the characteristics of different potential photosynthetic host organisms and recent advances in synthetic biology and discuss their utility for the (heterologous) production of (novel) terpenoids.
Significance Statement
Terpenoids are the most complex group of specialized metabolites, and many are economically important pharmaceuticals, aromatics and potential next‐generation biofuels. This review highlights the utility of photosynthetic organisms as platforms for the heterologous production of novel terpenoid structures, emphasizing how combinatorial biosynthesis and the activation of silent endogenous metabolism can be exploited to produce new‐to‐nature or tailor‐made compounds.
The bHLH transcription factor MYC2, together with its paralogues MYC3 and MYC4, is a master regulator of the response to the jasmonate (JA) hormone in Arabidopsis (Arabidopsis thaliana). In the ...absence of JA, JASMONATE ZIM (JAZ) proteins interact with the MYC proteins to block their activity. Understanding of the mechanism and specificity of this interaction is key to unravel JA signalling. We generated mutant MYC proteins and assessed their activity and the specificity of their interaction with the 12 Arabidopsis JAZ proteins. We show that the D94N mutation present in the atr2D allele of MYC3 abolishes the interaction between MYC3 and most JAZ proteins. The same effect is observed when the corresponding conserved Asp (D105) was mutated in MYC2. Accordingly, MYC2ᴰ¹⁰⁵ᴺactivated target genes in the presence of JAZ proteins, in contrast to wild‐type MYC2. JAZ1 and JAZ10 were the only JAZ proteins still showing interaction with the mutant MYC proteins, due to a second MYC interaction domain, besides the classical Jas domain. Our results visualize the divergence among JAZ proteins in their interaction with MYC proteins. Ultimately, the transferability of the Asp‐to‐Asn amino acid change might facilitate the design of hyperactive transcription factors for plant engineering.