Chemical genetic approaches to plant biology.

Synthetic chemistry and plant biology intersect in myriad ways. To date, however, the overlap of research methods between these two fields is limited. Outside of the agrochemical industry, most synthetic chemists simply view plants as sources of diverse and structurally complex organic molecules (i.e. natural products), frequently with exquisite biological activities. Little knowledge of plant biology is required to extract the desired natural products out of the plant tissues, in fact, pharmacognostic endeavors with natural products date back thousands of years (Parascandola, 1980; McTavish, 1987; Travis, 1989; Akerele, 1993). Similarly, most plant biologists rarely rely on synthetic chemistry to address day-to-day questions in their research. In other areas of the biological sciences, however, the synthetic chemistry/biology interface is substantially more developed. For example, the iterative synthesis and evaluation of collections of non-natural compounds is one of the cornerstones of the pharmaceutical sciences (Spencer, 1998). With the advent of combinatorial chemistry (Balkenhohl et al., 1996; Oliver and Abell, 1999) and high-throughput screening techniques over the past decade (Oldenburg, 1998; Engels and Venkatarangan, 2001), significantly larger synthetic compound libraries have been generated, and the pace of screening has dramatically escalated. Such techniques are now accessible to academic research labs (Tan et al., 1999) and have become central tools in the burgeoning field of chemical biology (Wells, 1999). Taking cues from the pharmaceutical industry, the agrochemical industry has also implemented combinatorial chemistry and high-throughput screening to uncover new herbicides and pesticides (Ridley et al., 1998). However, the systematic exploration of plant biological pathways with small molecule probes (molecular mass 700 D) is an approach still in its infancy. This general approach to biology, today called “chemical genetics,” is centered around the tenet that small organic molecules can be used like mutations in classical genetics to modulate protein functions and to assist in the delineation of biological pathways (Stockwell, 2000; Alaimo et al., 2001; Shogren-Knaak et al., 2001). Herein, we give a general introduction to chemical genetics, and through analysis of representative examples from the recent literature and our own laboratories, we highlight its potential as a wide-ranging tool for plant biology research.