The world's first plant signaling molecule regulation technology ″COR-Coronatine″ got the ICAMA registration for the first time

1. Origin of COR-Coronatine

Phytotoxins are generally secondary metabolites of microorganisms, and these active substances can interfere with the normal physiological functions of plant cells or directly kill cells [1, 2]. Plant pathogens utilize a range of phytotoxins to suppress host defenses and promote pathogenicity [3]. In 1977, Ichihara et al. isolated a compound from the culture medium of Pseudomonassyingaepv. atroppurpurea, which is a non-host-specific phytotoxin that can cause chlorosis in various plants and named it coronatine[4]. The global Chinese generic name of coronatine was led by the Chinese company Chengdu Newsun Crop Science Co., Ltd., approved by the China Standardization Technical Committee and acquired on May 3, 2013. COR-Coronatine is an analogue of the plant hormone methyl jasmonate (MeJA), which can regulate many physiological and chemical processes such as plant growth and development and stress resistance through the jasmonic acid pathway, and has broad application prospects in defoliation, control excessive growth, weeding, improve fruit coloring, increase fruit sugar content, seed germination under low temperature, abiotic stress resistance, disease resistance, insect resistance and etc.

2. Researches on Structure and Functions of COR-Coronatine

2.1 Structural characteristics and mechanism of actions of Coronatine 

Coronatine (C18H25NO4, molecular weight: 319 g/mol) is composed of coronamic acid (CMA) that contains α-amino acid and coronafacic acid (CFA) that with polyketide structure linked by amide bonds [5]. Several variants of Pseudomonas syringae can produce coronatine [6], which is a structural analogue of methyl jasmonate (MeJA) (Fig. 1), and can be recognized by the jasmonic acid receptor COI1 (COR-insensitive 1) in plants, activates the jasmonic acid signaling pathway, but COR is more active than MeJA in some functions [7] (Fig. 2).

Fig. 1: Structural Differences Between Coronatine(COR) And Methyl Jasmonate

The application of COR led to the discovery of the jasmonic acid receptor COI1 [8]. The researchers selected a COR-insensitive mutant coi1 (COR-insensitive 1) from tens of thousands of Arabidopsis thaliana. Subsequent in-depth studies found that an F-box protein in the mutant was inactivated, causing the JA signaling pathway unable to activate.

As shown in Figure 2, the receptor complex SCFCOI1, JAZ protein and transcription factor MYC constitute the core transduction mechanism of JA signaling. Under non-stress conditions, plant endogenous active JA-Ile accumulates at low levels, and JAZ protein inhibits the expression of early JA-responsive genes by recruiting the TPL transcriptional repression complex. However, in the presence of COR/JA-Ile, COR/JA-Ile can be bound by the JA receptor complex SCFCOI1, which promotes the degradation of JAZ protein through the 26S proteasome pathway, and then releases the MYC2 transcription factor to activate the JA signal response pathway, initiate downstream gene expression, and produce a series of physiological responses

Fig. 2: Mechanism of Actions of Coronatine

2.2 Physiological functions of coronatine

The physiological response of COR signal in plants depends on its concentration to a certain extent, showing different physiological effects at different concentrations.

High concentrations of COR (>10 μM) [10] can cause leaf chlorosis, release ethylene [11, 12], stimulate JA signaling and inhibit plant salicylic acid (SA)-dependent defense through antagonism [13], inhibit stomata closure to allow bacteria to enter the interior of plant leaves [14], cause chlorotic symptoms in infected plants, and inhibit plant cell wall defenses by interfering with the secondary metabolism [15]. Studies have shown that COR increases the accumulation of defense-related protease inhibitors and secondary metabolites, such as volatiles, nicotine, and alkaloids [16]. In addition, Toum et al. found in the studies of cotton defoliation that COR significantly improved the boll-opening without affecting the cotton boll weight, lint percentage and seed quality, and could be a potential cotton defoliant, with a different physiological mechanism of actions from that of the currently used Thidiazuron (TDZ) [17] (Fig. 3), so it can be used for defoliation and weed control.

Fig. 3: Potential Application of Coronatine in Cotton Defoliation [17]

Middle concentrations of COR (1-10 μM) can respond to mechanical damages [18], regulate fruit ripening [19] and dropping [20, 21]. Studies have shown that COR can induce the production of anthocyanins in fruits and increase the accumulation of endogenous proteins, carbohydrates and other substances in plants [12, 22] (Figure 4), so it can be widely used for fast and uniform fruit coloration, sugar improvement, and the accumulation of flavor substances, improving the commerciality of fruits. In addition, COR can also inhibit the increase of non-essential reactive oxygen species in plants, reduce the risk of fruit softening, rapid disintegration and spoilage of plant cells, and prolong the storage period and shelf life of fruits [10], so it can be used for improving the quality of post-harvest fruits during storage period.

Fig. 4: Coronatine Induces Synthesis of Anthocyanins [12]

Low concentrations of COR (<1 μM) can promote the expression of a series of defense genes and the synthesis of defense response chemicals under harsh environmental conditions such as low temperature, heat damage, salinity, drought, and pests and diseases [23]. Studies have shown that COR can regulate the ″immune″ and ″stress″ responses of plants, and improve plant resistance by maintaining plant leaf water content, promoting soluble protein synthesis, regulating cell osmotic pressure and antioxidant enzyme activity, and inducing protease inhibitors, alleviate damage to plants caused by stresses and increase crop yields. It plays an important role in resisting abiotic stresses [10], such as improving the low temperature resistance of soybean, the salt tolerance of cotton, and the cold resistance of cucumber [24], drought resistance of rice [25], corn [26], cauliflower [27] and soybean [28], and heat resistance of chickpea [29], and etc., making COR of a great potential for improving stress resistance and increasing crop yields.

Fig. 5: Coronatine Improves the Heat Resistance of Wheat in High Temperature Environment

3. COR-Coronatine Has Been Officially Registered For The First Time

According to China's Measures For The Administration Of Pesticide Registration, the pesticides produced, traded and used within the territory of China should obtain the Pesticide Registration Certificate issued by the Ministry of Agriculture and Rural Affairs of the People's Republic of China, encourage and support the registration of safe, efficient and economic pesticides, and accelerate the elimination of pesticides with high risks to agriculture, forestry, human and animal safety, agricultural product quality safety and ecological environment.

On September 3 in 2021, according to The Regulations On The Administration Of Pesticides and Measures For The Administration Of Pesticide Registration in China, and after strict technical review and also the review by the China Pesticide Registration Review Committee, ICAMA (Institute for the Control of Agrochemicals, MOA) approved the registration application of Coronatine 98% TC and  Coronatine 0.006% SL submitted by Chengdu Newsun Crop Science Co., Ltd and issued the Pesticide Registration Certificate (Figure 6). This means the Coronatine, a new type of cross-times plant growth regulator , was officially registered for the first time.

Fig. 6: Registration Certificate of Coronatine 98% TC and Coronatine 0.006% SL in ICAMA

4. Industrialization of COR-Coronatine

In the past, due to the low output and high cost, the industrialization of COR faced great difficulties. Supported by the key R&D plans of ″China's National 863 Program″ (National High Technology Research and Development Program) and ″13th Five Year Plan″, Chengdu Newsun cooperated with China Agricultural University Plant Growth Regulators Engineering Research Center of the Ministry of Education, after nearly 20 years of scientific research, have constructed a high-yield engineering strain with a yield of 5-10 times higher than that of conventional strains, solved the problem of fermentation potency, and finally established the world's first production line of Coronatine fermentation in Chengdu Newsun, break through the bottleneck of production technology by using green and efficient microbial fermentation technology and biosynthesis technology. At the same time, membrane concentration, recrystallization and other methods are used to optimize the extraction and purification process of Coronatine, and finally obtain the Coronatine technical grade with a purity of more than 98% [30-31], realizing the batch production of Coronatine to meet the huge market demand.

As the world’s first industrialized jasmonate plant growth regulator, COR-Coronatine can be approved by ICAMA, which shows that China attaches great importance to the development and application of new, safe, efficient and economical biological pesticides. Through the in-depth and continuous research and transformation application of Coronatine in the fields of soybean seed treatment under low-temperature, abiotic stress resistance and yield increasing, fruit coloring improvement and sugar content increasing for citrus, grape, apple and other fruits, defoliation and weeding, it will certainly play an active and extensive role in improving global food security, agricultural products yield and quality in the future, and will also accelerate the green transformation of global agriculture, promote green agricultural production, and make great contributions to the green and high-quality development of global agriculture.

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