The 2018 National Award for Science and Technology Progress for Research on Discovery of Selective New Target of Created Fungicide Phenamacril and Its Industrial Application
Source： Date：2019-03-01 Click：234
Winners：Zhou Mingguo, Ma Zhonghua, Hou Yiping, Wang Honglei, Chen Yu, Yang Rongming, Duan Yabing, Diao Yamei, Zheng Zhaoyang, and Guan Chenghong
Fusarium species cause head scab in wheat, bakanae disease in rice and many other crop diseases leading to serious yield loss. Forethemore, most Fusarium species produce various types of mycotoxins contaminating agricultural products that in turn threaten food safety. Due to lack of crop varieties with high resistance to these fungi and development of their resistance to fungicides, Fusarium spp. have become increasingly serious crop pathogens hard to deal with. In meeting this important social demand, the researchers of the present program have studied and found that myosin-5 is an important new target for fungicides, illuminated the selective mechanism of phenamacril, a Fusarium-specific myosin inhibitor, identified the molecular mechanism of sensitivity and the risk of resistance of myosin inhibitor, developed key technology of safe and efficient prevention of Fusarium spp. damaging rice and wheat crops by management of phenamacril resistance risik; all of these efforts have contributed to innovation in agricultural technology extension, promotion of new pesticide development and control of the Fusarium diseases and their mycotoxins.
(1) Discovered myosin-5 as a selective target of fungicides and the toxicological mechanism of phenamacril. The researchers have integrated the traditional and modern experimental technologies; found myosin-5 to be an extremely important new target of fungicides, revealed the toxicological mechanisms of interfering in ATPase activity, destroying cytoplast transport and preventing cell development and DON synthesis of phenamacril by inhibiting the myosin-5, an indispensable element for life; and identified the factors, which are related to the functions of the myosin and regulate the toxicology of phenamacril, including the myosin passenger-protein gene, the fimbrin gene, the myosin-2B gene, and the redox pathway. The on Fungicide Resistance Action Committee (FRAC) has classified myosin as the first class-three extremely safe new selective target of fungicides after zymoprotein and structural protein in the history of fungicide development and nicknamed it “motor protein” with a “B6”code.
(2) Identified the molecular mechanism of sensitivity and the risk of resistance of the myosin-5 inhibitor. The researchers have found that the selectivity of phenamacril is based on the differentiation of myosin-5 in different species. The phenamacril has only selective antifungal activity to Fusarium spp. in which the amino acid sequence of target protein has 97% similarity with myosin-5 of Fusarium graminearum, including those causing head scab in wheat and bakanae disease in rice The myosin-5 has at least 12 amino acid residues with total mutation frequency of 23.9% that confer different resistance levels to phenamacril. Based on these results, the FRAC has given the resistance management strategies of phenamacril an individual code of 47, providing scientific motivation for application of the myosin inhibitor.
(3) Developed the first new process of green synthesis of the myosin inhibitor phenamacril. They have developed a new process of preparing the intermediate ethyl benzimidate hydrochloride for synthesis of phenamacril using endophytic HCL of the reaction system as catalyst, which reduces phenamacril synthesis into two steps and avoids the dangerous procedures of chlorination, hyperthermal degradation and ammoniation, but increases the overall yield to above 85% with the content of the active compound higher than 95% and the reduction of cost by over 40%.
(4) Innovated extension of the new technology for efficient and safely reduced application of fungicide for sustainable prevention and control of the Fusarium disaeses in rice and wheat, and producing great social and economic benefit. Based on the toxicology and resistance risk of phenamacril, the researchers of the present program have developed a series of new technologies of higher effect and lower amount of fungicide use by widening the anti-fungus spectrum and postponing the fungicide resistance, reducing the amount of the fungicide by over 60% in comparison with that of carbendazim application. In the past three years, the extension of application of the series of phenamacril products for prevention and control of head scab in wheat and bakanae disease in rice has covered over 90 million mu of farmland, which has helped increase the grain yield of over 3.4 million tons, decrease the micotoxin by 85%, and avoid a loss of 22 billion RMB for farmers. This achievement has made the technology developed here a well-known first choice of controlling Fusarium head blight and rice Bakanae diseases.
The researchers have published 39 research articles, have been issued 10 patents for invention, have been editor-in-chief of four monographs and co-editors of three (including two in English), and have hosted or give speeches at over 70 conferences, including six invited key-note speeches at international conferences. To sum up, the results of this program are important contributions to raising the scientific levels of pesticide creation and prevention and control of the major crop diseases that caused by Fusarium spp. in China