Plant chemical biology: are we meeting the promise?

Abstract

As an early adopter of plant chemical genetics to the study of endomembrane trafficking, we have observed the growth of small molecule approaches. Within the field, we often describe the strengths of the approach in a broad, generic manner, such as the ability to address redundancy and lethality. But, we are now in a much better position to evaluate the demonstrated value of the approach based on examples. In this perspective, we offer an assessment of chemical genetics in plants and where its applications may be of particular utility from the perspective of the cell biologist. Beyond this, we suggest areas to be addressed to provide broader access and enhance the effectiveness of small molecule approaches in plant biology.

Chemical Genetics Uncovers Novel Inhibitors of Lignification, Including p-Iodobenzoic Acid Targeting CINNAMATE-4-HYDROXYLASE

“…On the other hand, these compounds could specifically inhibit one particular isozyme of an enzyme family, resulting in a visible reduction in Wiesner staining of seedlings, whereas the inhibition might not be sufficient to inhibit lignification in Casparian strips of roots or in TE-induced cell cultures. Although overcoming gene redundancy is one of the most cited advantages of chemical genetics, precedents exist of inhibitors that do not target all members of a conserved family (Hicks and Raikhel, 2014). Jarin-1, for instance, selectively inhibits jasmonate-Ile formation by specifically interacting with JASMONATE RESISTANT1 of the GH3 enzyme family (Meesters et al, 2014).…”

“…Finally, compounds can be applied easily to essentially any plant model system or crop, whereas a genetic perturbation needs to be introduced in one genotype at a time (Tóth and van der Hoorn, 2010). Thanks to these characteristics, chemical biology has been successful for drug discovery (Cong et al, 2012), and it is becoming increasingly more popular to discover molecular mechanisms of physiological processes in plants (De Rybel et al, 2009Dejonghe and Russinova, 2014;Hicks and Raikhel, 2014).…”

Chemical regulators of plant hormones and their applications in basic research and agriculture*

“…Chemical genetics is a powerful tool in biology studies that utilizes small molecules screened from chemical libraries to decipher biological processes. Compared to conventional genetics approaches, chemical genetics has several important advantages, including that it can overcome the lethality of certain mutations and gene redundancy [394][395][396]. In the above sections, we summarized numerous chemical regulators that were screened from chemical libraries or were rationally designed ( Figures 1-10, and Table 1).…”

Facile high-throughput forward chemical genetic screening by in situ monitoring of glucuronidase-based reporter gene expression in Arabidopsis thaliana

“…For example, small molecules can in principle target multiple members of a protein family or, alternatively, the effects they exert can be temporally controlled and possibly reversed by withdrawing the chemical from the system. However, in contrast to animal systems, which are nurtured from drug discovery programs and cancer research, the application of chemical genetics in basic plant research stands quite in contrast to industrial applications such as pesticide (herbicide and fungicide) discovery and has only recently found broader application as documented in a number of reviews (Blackwell and Zhao, 2003 ; Raikhel and Pirrung, 2005 ; Kaschani and van der Hoorn, 2007 ; Hicks and Raikhel, 2009 , 2012 , 2014 ; Tóth and van der Hoorn, 2010 ).…”