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Research Progress

Optimized Abscisic Acid Analogs with Higher-than-natural Hormone Activities Identified

Nov 06, 2017

Drought is a major threat to crop production worldwide, and effective methods to mitigate its adverse effects have long been urgently required. Under natural conditions, land plants use abscisic acid (ABA), one of the phytohormones, to cope with drought and other abiotic stresses. Plants respond to drought stress by physiological and molecular reprogramming rearrangements, including stomatal closure and the induction of drought-responsive genes.

However, the rapid catabolism and chemical instability of ABA have weakened its application in the field, thus prompting researchers to search for other small alternative compounds that can function as ABA analogs but with increased chemical and/or physiological stability. One such compound, AM1, was previously identified as an ABA receptor agonist, although it was less effective than ABA in enhancing drought stress resistance in plants.

Recently, a study led by Prof. ZHU Jiankang at Shanghai Institute of Plant Physiology and Ecology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences, demonstrated that structure-based design is a powerful approach to create optimized compounds that are much more potent than ABA. This study, published in Nature Communications, also showed that the combination of these compounds with overexpression of an ABA receptor will be very effective in helping plants combat drought stress.

Researchers carried out a structure-guided optimization of AM1 based on the crystal structure of the ligand-receptor complex, and found that adding fluorine atoms in the benzyl ring of the AM1 backbone improves its binding to ABA receptors (named PYL) and makes it much more capable in protecting plants from drought stress. These new compounds, called AMFs, have receptor-binding affinities that are generally an order of magnitude higher than that of ABA.

By studying the structures of PYL2-AMFs complexes, they revealed that the added fluorine atoms increase the number of hydrogen bonds between the compounds and the surrounding amino acid residues in the PYL2 ligand-binding pocket. Like ABA, AMFs were found to promote stomatal closure and induce the expression of stress-responsive genes, and the effects of AMFs persist longer than those of ABA. Therefore, when sprayed on Arabidopsis and soybean plants, AMFs showed comparably more positive effects than ABA or AM1 in conferring drought resistance. 

Further study demonstrated that transgenic overexpression of PYL2 in plants also offered up increased drought resistance. However, the increase in drought resistance could be maximized when AMFs were applied to Arabidopsis and soybean PYL2-overexpression transgenic plants, revealing a synergistic effect between AMF treatment and PYL2 overexpression.

This study showed the potential of combining chemical and genetic approaches and paved the way for protecting plants under drought stress.

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