Harnessing synthetic chemistry to probe and hijack auxin signaling

: Contents Summary 417 I. Introduction 417 II. Auxin analogs 1: Plant growth regulators 418 III. Auxin analogs 2: Molecular genetics and chemical biology 418 IV. Auxin analogs 3: Structure-guided chemical design 418 V. Auxin analogs 4: Synthetic orthogonal auxin-TIR1 pair 420 VI. Conclusions and future perspectives 422 Acknowledgements 422 References 423 SUMMARY: Plant biologists have been fascinated by auxin - a small chemical hormone so simple in structure yet so powerful - which regulates virtually every aspect of plant growth, development and behavior. Synthetic chemistry has played a major role in unraveling the physiological effects of auxin and the application of synthetic analogs has had a dramatic effect on tissue culture, horticulture and the agriculture of economically relevant plant species. Chemical genetics of the model plant, Arabidopsis thaliana, has helped to elucidate the nuclear auxin signaling pathway mediated by the receptor, TIR1, and opened the door to structure-guided, rational designs of auxin agonists and antagonists. Further improvement and tuning of such analogs has been achieved through derivatization and screening. Finally, by harnessing synthetic chemistry and receptor engineering, an orthogonal auxin-TIR1 pair has been created and developed, enabling spatiotemporal control of auxin perception and response. This synergism of chemistry, biology and engineering sparks new ideas and directions to delineate, uncover and manipulate auxin signaling.