The term “chemical biology” is commonly associated with research at the interface
of chemistry and biology, as revealed by a recent census amongst scientists working
in the field (Anonymous, 2015). Distinctively, as a truly interdisciplinary science,
chemical biology combines scientific concepts and experimental approaches from both
of its parent fields to understand molecular mechanisms in complex biological systems.
New chemical tools and technologies are developed to dissect, visualize and manipulate
biological processes or pathways and, conversely, studying biological systems may
foster the development of new chemical principles. Although chemical biology has so
far found most applications in pharmaceutical drug discovery, the search for novel
bioactive small molecules that produce phenotypes in plants is also an established
strategy in the agrichemical industry. In these approaches, the primary focus was
laid on the discovery and improvement of herbicides, pesticides and other agriculturally
useful compounds.
Upon recognition of the opportunities that bioactive small molecules may provide to
basic plant biology research, in particular in combination with genetic strategies,
the research field of plant “chemical genetics” emerged and has grown substantially
over the past decade. Essentially, small molecules are utilized to generate recognizable
phenotypes in a manner that is analogous to forward mutation genetics. However, chemical
genetics has the potential to circumvent inherent problems of classical, forward genetics,
such as lethality, pleiotropy or redundancy of gene functions because small molecules
can be applied in a conditional, dose-dependent and reversible manner. The persistent
challenge remains to identify the cognate target of such bioactive chemicals to discover
the genes, proteins or pathways that are responsible for a given phenotype. Likewise,
chemicals can be combined with other profiling technologies, such as genomics, proteomics
or metabolomics. There are now clear examples of important, fundamental discoveries
originating from plant chemical biology/genetics that demonstrate the power of this
experimental approach.
The current issue on plant chemical biology provides a snapshot of the field, comprising
review articles, perspectives and original research articles that both novices and
experts may find useful. In their perspective article, Hicks and Raikhel focus on
successful applications and the current challenges that the field of plant chemical
biology/genetics faces as it matures. The discovery of novel bioactive chemicals is
generally achieved by screening of compound collections (so-called chemical libraries),
using robust and reliable phenotypes. The design and execution of such screening campaigns
is outlined in a review article by Serrano et al. Here, in particular the newcomer
will find useful recommendations that will help to avoid common pitfalls. In addition,
recent success stories of plant chemical biology are highlighted, which may serve
as teaching examples for implementation of future chemical biology projects. Along
the same lines, in an original research article, Halder and Kombrink describe a facile
bioassay for quantifying β-glucuronidase (GUS) activity in situ, which may turn out
as a useful screening tool. Importantly, the methodology can be adopted for any transgenic
Arabidopsis line harboring an inducible (or repressible) GUS reporter, and such lines
are available for numerous developmental stages or signaling pathways. Once a chemical
screening campaign has provided a new bioactive compound, the ultimate goal is to
identify its mode of action and molecular target (or targets). Dejonghe and Russinova
discuss in their review article different strategies for direct target identification,
the current ones as well as the emerging ones, which have not yet found broad application
in plant biology. Despite all recent progress, this still remains the most challenging,
laborious and time-consuming step of chemical biology projects.
A recurring theme of plant chemical biology has been the search for, and application
of bioactive small molecules in plant hormone signaling. In this sector a large assortment
of chemicals has been identified and used as agonists or antagonists of phytohormones
and thereby provided new insights into plant hormone biology. Two review articles
by Rigal et al. and Fonseca et al. summarize some prominent examples of using chemical
biology/genetic strategies in plant hormone research. Redundancy is largely avoided,
as the former article focuses on signaling mediated by abscisic acid (ABA), salicylic
acid (SA), auxin (IAA), cytokinin (CK), and brassinosteroids (BR), while the latter
covers jasmonate (JA) signaling as well as phytohormone homeostasis, transport and
hormonal crosstalk. In addition, Nakamura and Asami provide a focused review on chemical
regulation of strigolactone (SL) signaling. Strigolactones have recently attracted
much attention, as they are multifunctional molecules that not only act as phytohormones,
inhibiting shoot branching, but also serve as rhizospheric communication signals between
plant and symbiotic fungi and/or parasitic plants from the Striga and Orobanche genera.
Identification or design of inhibitors of SL biosynthesis or SL receptors is a potential
method to control these devastating and agronomically important root parasites. Finally,
Almeida-Trapp et al. describe in an original research article the development and
validation of an analytic method for quantification of six phytohormones that are
frequently associated with stress responses, IAA, ABA, SA, JA, jasmonoyl-isoleucine
(JA-Ile), and 12-oxo-phytodienoic acid (OPDA). Such a critically evaluated and validated
method is obviously important for all plant hormone related work allowing direct comparison
of hormone levels established in different laboratories.
A second favorite topic of plant chemical biology research has been plant–pathogen
interactions and plant immune responses. Naturally occurring small molecules such
as toxins produced by pathogens or phytoalexins produced by plants upon infection
serve to intercept with growth and development of plants and pathogens, respectively.
Other, not-so-small molecules (i.e., peptides) are involved in the initial perception
of pathogen invasion by specific plant receptor-like kinases. Mott et al. discuss
in their review the diverse roles of apoplastic molecules (peptides and small molecules)
in modulating plant–pathogen interactions. A different view on such interactions is
provided by Bektas and Eulgem who discuss in their review the function of synthetic
elicitors that induce plant defense responses, but are distinct from known natural
elicitors of plant immunity. A large variety of such compounds has been identified
through screening efforts or targeted synthesis as analogs of natural compounds such
as salicylic acid. They are attractive for basic research, allowing functional dissection
of the plant immune system, as well as for applied purposes, as they can protect crop
plants from diseases. Stokes and McCourt develop the applied aspect of chemicals in
biological systems (here chemistry and agricultural biotechnology) a step further
by predicting a future trend toward “personalized” agriculture, which essentially
means to develop highly selective and species-specific herbicides and growth regulators.
Indeed, recent success stories in plant chemical biology demonstrate that the corresponding
technologies and tools are available. Thus, the development of tailored chemicals
that modify traits of crop species or target specific classes of weeds or pests by
collaboration of applied and academic research groups (in analogy to the current drug
discovery process) may provide a bright future for plant chemical biology.
Author contributions
EK served as editor of the research topic “When Chemistry Meets Biology – Generating
Innovative Concepts, Methods and Tools for Scientific Discovery in the Plant Sciences”
and wrote this editorial. MK served as editor of the research topic “When Chemistry
Meets Biology – Generating Innovative Concepts, Methods and Tools for Scientific Discovery
in the Plant Sciences” and wrote this editorial.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial
or financial relationships that could be construed as a potential conflict of interest.