MYC2: A Master Switch for Plant Physiological Processes and Specialized Metabolite Synthesis

Phytohormones are important regulators of plant growth and development. In response to damage, plants generally integrate phytohormone signaling pathways to trigger immune defense and repair responses throughout the plant body. Particularly, jasmonic acid (JA) signaling is a core signaling pathway that becomes activated in response to plant damage. After the plant is damaged, a large amount of JA is produced, which is then transformed into (+)-7-iso-jasmonoyl-L-isoleucine (JA-Ile) with biological activity. JA-Ile promotes the formation of the SCF-COI1-JAZ coreceptor complex, degrades JAZ (Jasmonate ZIM-domain) through 26S proteasome ubiquitination, and relieves JAZ's inhibition of MYC2, thereby activating the transcription of MYC2 downstream genes, thus triggering plant defense and repair. As a JA signaling hub, MYC2 participates in multiple signaling pathway-networks that integrate light signaling, hormone signaling, natural product synthesis, and the complex processes of plant growth and development. In addition, JA not only activates the defense response of the plant itself, but also enhances the content of linalool and β-ocimene or induces the release of other volatile organic compounds, such as shikimic acid derivatives, to enhance the resistance of adjacent plants to the attack of arthropod herbivores.

The review synthesizes current knowledge on MYC2-mediated JA signaling and its integration with other pathways. Core JA signaling: JA-Ile is perceived by COI1, enabling the SCFCOI1-JAZ co-receptor to target JAZ repressors for ubiquitin-dependent degradation, releasing MYC2 to activate JA-responsive genes. MYC2, a bHLH transcription factor, contains an N-terminal JAZ-interaction and activation domain and a C-terminal DNA-binding bHLH domain that recognizes G-box elements (CACGTG). JAZ proteins repress MYC2 via NINJA-TPL co-repressors and histone deacetylation (e.g., HDA6), and a single amino acid change in MYC2/MYC3 can disrupt JAZ interaction. MYC2 forms homo-/heterodimers with MYC3/4/5 and recruits chromatin regulators via MED25, including HAC1, GCN5, and SPLAYED, to modulate histone acetylation and nucleosome remodeling at target promoters; it also helps recruit the pre-initiation complex and RNA Pol II. MYC2 induces JA-responsive bHLH repressors (MTB1–3) establishing negative feedback, with LUH acting as a scaffold with MED25 and HAC1 to promote H3K9ac at JAZ2 and LOX2. Crosstalk: ABA signaling connects via direct PYL6–MYC2 interaction; ethylene antagonism involves MYC2 interaction with EIN3/EIL1, reducing their DNA binding; GA DELLAs bind JAZs, freeing MYC2; SA antagonism involves NPR1 interaction with MYC2, disrupting MYC2–MED25 to suppress JA-responsive genes. Light and circadian inputs: blue-light CRY1/CRY2 induce MYC2/4, integrating with photomorphogenesis (HY5) and SPA1 regulation; circadian control modulates JA biosynthesis and MYC2 activity. Post-translational regulation: blue light enhances SUMOylation of MYC2 (K139, K480), stabilizing it and modulating DNA binding and interaction with PUB10; CUL3-BPM E3 ligases target MYC factors for degradation, forming additional negative feedback layers. Functional roles reviewed include: (1) Biotic/abiotic stress—MYC2 networks mediate herbivore and pathogen defenses (terpene synthases, flavonoids, PPCs/SGAs), water-spray-induced JA via ORA47/bHLH19/ERF109, drought (ABA-dependent rd22, ADH), salt (MYC2-like→OsCYP2), cold tolerance (MYC2→CBFs, BADH-like for glycine betaine), and modulation by nematode RALF–FER signaling. (2) Growth and development—leaf vein development and senescence (TRP, Dof2.1 loop, CAT2 repression; SAG and photosynthesis gene regulation), root meristem and regeneration (PLT1/2 repression; ERF115/109 induction; auxin biosynthesis links), nutrient uptake and nodulation, fruit ripening (ethylene biosynthesis via ACS/ACO and ERF modules), ovule PCD (SAG39), seed storage protein accumulation (MYC2/3/4), spikelet morphogenesis (OsJAZ1–OsCOI1b–OsMYC2→OsMADS1), pollen development (carbohydrate metabolism genes), and sex differentiation in chestnut. (3) Specialized metabolism—direct/indirect MYC2 regulation of key enzymes and TFs for paclitaxel (Taxus; ERF12/15; taxadiene synthase), artemisinin (Artemisia; CYP71AV1, DBR2), tanshinones/phenolic acids (Salvia; CYP98A14, SmGGPPS), vinblastine (Catharanthus; ORCA2/3/4), gossypol (cotton; CYP71BE79), and triterpenoid saponins (Psammosilene); negative regulation of triptolide (Tripterygium). The review also surveys synthetic biology applications, proposing a JA–JAZ–MYC2 conditional molecular switch controlling MYC2-responsive promoters across microbial and plant chassis, artificial chromosome strategies, co-culture systems (E. coli–S. cerevisiae) to overcome P450 expression limits, and inducible ON/OFF control for pathway optimization.

• MYC2 is a central effector of JA signaling, released from JAZ repression upon JA-Ile-triggered SCFCOI1-JAZ degradation, and activates JA-responsive genes via G-box binding.
• MYC2 integrates with chromatin machinery (MED25, HAC1, GCN5, SPLAYED) and establishes feedback regulation through MTB bHLH repressors and LUH-mediated coactivation, fine-tuning JA responses.
• Extensive hormonal and environmental crosstalk: MYC2 interacts with ABA (PYL6), ethylene (EIN3/EIL1), GA (DELLA–JAZ competition), and SA (NPR1), and is modulated by light/circadian cues (CRY1/2, SPA1, HY5), SUMOylation (K139/K480), and CUL3-BPM ubiquitin ligases, providing multilayered control of defense and development.
• Biotic stress: MYC2 and related MYCs regulate herbivore and pathogen defense via induction of terpene synthases (TPS), flavonoids, PPCs and SGAs, PR genes, and PDF1.2; they contribute to species-specific resistances (e.g., rice OsMYC2 to planthoppers; tomato immunity; cotton gossypol pathway).
• Abiotic stress: MYC2 enhances drought (rd22, ADH), salt (OsCYP2 via MYC2-like), cold tolerance (CBF pathways, BADH-like for glycine betaine), and responds to mechanical stimuli (water spray via ORA47/ERF109/bHLH19).
• Development: MYC2 controls leaf venation and senescence (Dof2.1 loop; CAT2 repression; SAG genes), root meristem maintenance and regeneration (PLT1/2 repression; ERF115/109 induction), nutrient uptake, fruit ripening (ACS/ACO via ERF2/3), ovule PCD (SAG39), seed storage protein accumulation (MYC2/3/4 redundancy), spikelet morphogenesis (OsJAZ1–OsMYC2→OsMADS1), pollen maturation, and sex differentiation (chestnut).
• Specialized metabolism: MYC2 directly/indirectly regulates key enzymes/TFs for high-value metabolites—paclitaxel (Taxus; ERFs; taxadiene synthase), artemisinin (CYP71AV1, DBR2), tanshinones/phenolic acids (CYP98A14, SmGGPPS), vinblastine (ORCAs), gossypol (CYP71BE79), triterpenoid saponins; can also act as a negative regulator (triptolide in Tripterygium).
• Synthetic biology prospect: A modular JA–JAZ–MYC2 inducible switch can drive MYC2-responsive promoters within artificial chromosomes to coordinate entire pathways in microbial (E. coli, S. cerevisiae) or plant chassis (Nicotiana benthamiana, crops, microalgae), enabling precise ON/OFF control, reduced metabolic burden, and improved yields of complex plant natural products (e.g., paclitaxel co-culture strategies; vinblastine and artemisinic acid precedents).

The review frames MYC2 as a master regulatory node that translates JA accumulation into coordinated transcriptional programs across defense, development, and specialized metabolism. By detailing MYC2’s interactions with repressors (JAZ/NINJA/TPL), coactivators (MED25, HAC1, GCN5, SPLAYED, LUH), and its integration with ABA, ET, GA, SA, and light/circadian pathways, the article explains how plants achieve context-dependent responses to biotic and abiotic stimuli. The compiled evidence across multiple species shows MYC2’s direct regulation of key biosynthetic genes and secondary TFs, explaining observed metabolite accumulation (terpenoids, alkaloids, phenylpropanoids) under stress or developmental cues. Translating these insights, the authors propose leveraging the inducible, tightly controlled JA–JAZ–MYC2 axis as a molecular switch in synthetic biology to temporally and quantitatively regulate entire biosynthetic pathways on artificial chromosomes in suitable chassis. This addresses challenges of low natural yields and complex pathway regulation, providing a route to scalable production of high-value metabolites while minimizing host burden through inducible expression.

This review consolidates MYC2’s central role in JA signaling and its extensive crosstalk, highlighting MYC2 as a key regulator of plant stress responses, growth and development, and specialized metabolite biosynthesis. It identifies direct MYC2 targets and secondary transcriptional cascades that underlie production of therapeutically important compounds (e.g., paclitaxel, artemisinin, vinblastine). The authors outline a synthetic biology strategy in which a JA–JAZ–MYC2 inducible molecular switch drives MYC2-responsive promoters on artificial chromosomes to coordinate complex pathways in microbial and plant chassis, enabling precise ON/OFF control for efficient metabolite production. Future research should focus on: refining MYC2-based switches (orthogonality, dynamic range), expanding validated MYC2-responsive promoters across species, integrating pathway compartmentalization (e.g., P450 expression), optimizing chassis co-cultures, and validating scalability and stability for industrial bioproduction.

The article is a narrative review and does not present new experimental datasets; conclusions rely on published studies from diverse species, which may limit generalizability. While proposing a JA–JAZ–MYC2 molecular switch for synthetic biology, practical implementation faces challenges including: host-specific differences in MYC2/JAZ/COI1 function, potential interference from endogenous JA signaling, limited availability of fully characterized MYC2-responsive promoters for all pathway genes, difficulties expressing membrane-bound/cytochrome P450 enzymes (particularly in prokaryotes), metabolic burden and toxicity of intermediates, and stability/containment of large artificial chromosomes. Empirical validation and optimization in selected chassis and pathways remain necessary.