Bikinin-like inhibitors targeting GSK3/Shaggy-like kinases: characterisation of novel compounds and elucidation of their catabolism in planta

详细信息    查看全文

• 作者：Wilfried Rozhon (7) (8) (9)
  Wuyan Wang (10) (8)
  Franz Berthiller (11)
  Juliane Mayerhofer (7)
  Tingting Chen (8)
  Elena Petutschnig (12) (7)
  Tobias Sieberer (13) (9)
  Brigitte Poppenberger (8) (9)
  Claudia Jonak (7)
  
  7. GMI-Gregor Mendel Institute of Molecular Plant Biology ; Austrian Academy of Sciences ; Vienna Biocenter ; Dr. Bohr-Gasse 3 ; Vienna ; 1030 ; Austria
  8. Biotechnology of Horticultural Crops ; Technische Universit盲t M眉nchen ; Liesel-Beckmann-Stra脽e 1 ; Freising ; 85354 ; Germany
  9. Max F. Perutz Laboratories ; Department of Microbiology ; Immunobiology and Genetics ; University of Vienna ; Vienna ; 1030 ; Austria
  10. Plant Biochemistry ; ETH Z眉rich ; Universit盲tsstr. 2 ; Z眉rich ; 8092 ; Switzerland
  11. Center for Analytical Chemistry ; Department of Agrobiotechnology ; University of Natural Resources and Life Sciences ; Konrad Lorenz Stra脽e 20 ; Tulln ; 3430 ; Austria
  12. Albrecht-von-Haller-Institute of Plant Sciences ; Department of Plant Cell Biology ; Georg-August-University G枚ttingen ; Julia-Lermontowa-Weg 3 ; G枚ttingen ; 37077 ; Germany
  13. Department of Plant Sciences ; Research Unit Plant Growth Regulation ; Technische Universit盲t M眉nchen ; Liesel-Beckmann-Stra脽e 1 ; Freising-Weihenstephan ; 85354 ; Germany
  
• 关键词：Brassinosteroid ; GSK ; 3/shaggy ; like kinase ; Inhibitor ; Protein phosphorylation ; Signal transduction
• 刊名：BMC Plant Biology
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：14
• 期：1
• 全文大小：1,418 KB
• 参考文献：1. Clouse, SD (2011) Brassinosteroid signal transduction: from receptor kinase activation to transcriptional networks regulating plant development. Plant Cell 23: pp. 1219-1230 1105/tpc.111.084475" target="_blank" title="It opens in new window">CrossRef
  2. Choe, S, Tanaka, A, Noguchi, T, Fujioka, S, Takatsuto, S, Ross, AS, Tax, FE, Yoshida, S, Feldmann, KA (2000) Lesions in the sterol delta reductase gene of Arabidopsis cause dwarfism due to a block in brassinosteroid biosynthesis. Plant J 21: pp. 431-443 CrossRef
  3. Gachotte, D, Husselstein, T, Bard, M, Lacroute, F, Benveniste, P (1996) Isolation and characterization of an Arabidopsis thaliana cDNA encoding a delta 7-sterol-C-5-desaturase by functional complementation of a defective yeast mutant. Plant J 9: pp. 391-398 CrossRef
  4. Choe, S, Noguchi, T, Fujioka, S, Takatsuto, S, Tissier, CP, Gregory, BD, Ross, AS, Tanaka, A, Yoshida, S, Tax, FE, Feldmann, KA (1999) The Arabidopsis dwf7/ste1 mutant is defective in the delta7 sterol C-5 desaturation step leading to brassinosteroid biosynthesis. Plant Cell 11: pp. 207-221
  5. Choe, S, Dilkes, BP, Gregory, BD, Ross, AS, Yuan, H, Noguchi, T, Fujioka, S, Takatsuto, S, Tanaka, A, Yoshida, S, Tax, FE, Feldmann, KA (1999) The Arabidopsis dwarf1 mutant is defective in the conversion of 24-methylenecholesterol to campesterol in brassinosteroid biosynthesis. Plant Physiol 119: pp. 897-907 1104/pp.119.3.897" target="_blank" title="It opens in new window">CrossRef
  6. Kauschmann, A, Jessop, A, Koncz, C, Szekeres, M, Willmitzer, L, Altmann, T (1996) Genetic evidence for an essential role of brassinosteroids in plant development. Plant J 9: pp. 701-713 CrossRef
  7. Choe, S, Dilkes, BP, Fujioka, S, Takatsuto, S, Sakurai, A, Feldmann, KA (1998) The DWF4 gene of Arabidopsis encodes a cytochrome P450 that mediates multiple 22alpha-hydroxylation steps in brassinosteroid biosynthesis. Plant Cell 10: pp. 231-243
  8. Szekeres, M, Nemeth, K, Koncz-Kalman, Z, Mathur, J, Kauschmann, A, Altmann, T, Redei, GP, Nagy, F, Schell, J, Koncz, C (1996) Brassinosteroids rescue the deficiency of CYP90, a cytochrome P450, controlling cell elongation and de-etiolation in Arabidopsis. Cell 85: pp. 171-182 CrossRef
  9. Li, J, Nagpal, P, Vitart, V, McMorris, TC, Chory, J (1996) A role for brassinosteroids in light-dependent development of Arabidopsis. Science 272: pp. 398-401 1126/science.272.5260.398" target="_blank" title="It opens in new window">CrossRef
  10. Kim, GT, Fujioka, S, Kozuka, T, Tax, FE, Takatsuto, S, Yoshida, S, Tsukaya, H (2005) CYP90C1 and CYP90D1 are involved in different steps in the brassinosteroid biosynthesis pathway in Arabidopsis thaliana. Plant J 41: pp. 710-721 1111/j.1365-313X.2004.02330.x" target="_blank" title="It opens in new window">CrossRef
  11. Nomura, T, Kushiro, T, Yokota, T, Kamiya, Y, Bishop, GJ, Yamaguchi, S (2005) The last reaction producing brassinolide is catalyzed by cytochrome P-450聽s, CYP85A3 in tomato and CYP85A2 in Arabidopsis. J Biol Chem 280: pp. 17873-17879 CrossRef
  12. Li, J, Chory, J (1997) A putative leucine-rich repeat receptor kinase involved in brassinosteroid signal transduction. Cell 90: pp. 929-938 CrossRef
  13. Li, J, Wen, J, Lease, KA, Doke, JT, Tax, FE, Walker, JC (2002) BAK1, an Arabidopsis LRR receptor-like protein kinase, interacts with BRI1 and modulates brassinosteroid signaling. Cell 110: pp. 213-222 CrossRef
  14. Nam, KH, Li, J (2002) BRI1/BAK1, a receptor kinase pair mediating brassinosteroid signaling. Cell 110: pp. 203-212 CrossRef
  15. Tang, W, Kim, TW, Oses-Prieto, JA, Sun, Y, Deng, Z, Zhu, S, Wang, R, Burlingame, AL, Wang, ZY (2008) BSKs mediate signal transduction from the receptor kinase BRI1 in Arabidopsis. Science 321: pp. 557-560 1126/science.1156973" target="_blank" title="It opens in new window">CrossRef
  16. Kim, TW, Guan, S, Sun, Y, Deng, Z, Tang, W, Shang, JX, Sun, Y, Burlingame, AL, Wang, ZY (2009) Brassinosteroid signal transduction from cell-surface receptor kinases to nuclear transcription factors. Nat Cell Biol 11: pp. 1254-1260 CrossRef
  17. Jonak, C, Hirt, H (2002) Glycogen synthase kinase 3/SHAGGY-like kinases in plants: an emerging family with novel functions. Trends Plant Sci 7: pp. 457-461 CrossRef
  18. Li, J, Nam, KH (2002) Regulation of brassinosteroid signaling by a GSK3/SHAGGY-like kinase. Science 295: pp. 1299-1301
  19. Perez-Perez, JM, Ponce, MR, Micol, JL (2002) The UCU1 Arabidopsis gene encodes a SHAGGY/GSK3-like kinase required for cell expansion along the proximodistal axis. Dev Biol 242: pp. 161-173 CrossRef
  20. Rozhon, W, Mayerhofer, J, Petutschnig, E, Fujioka, S, Jonak, C (2010) ASKtheta, a group-III Arabidopsis GSK3, functions in the brassinosteroid signalling pathway. Plant J 62: pp. 215-223 1111/j.1365-313X.2010.04145.x" target="_blank" title="It opens in new window">CrossRef
  21. Vert, G, Chory, J (2006) Downstream nuclear events in brassinosteroid signalling. Nature 441: pp. 96-100 CrossRef
  22. Dal Santo, S, Stampfl, H, Krasensky, J, Kempa, S, Gibon, Y, Petutschnig, E, Rozhon, W, Heuck, A, Clausen, T, Jonak, C (2012) Stress-induced GSK3 regulates the redox stress response by phosphorylating glucose-6-phosphate dehydrogenase in Arabidopsis. Plant Cell 24: pp. 3380-3392 1105/tpc.112.101279" target="_blank" title="It opens in new window">CrossRef
  23. Piao, HL, Lim, JH, Kim, SJ, Cheong, GW, Hwang, I (2001) Constitutive over-expression of AtGSK1 induces NaCl stress responses in the absence of NaCl stress and results in enhanced NaCl tolerance in Arabidopsis. Plant J 27: pp. 305-314 CrossRef
  24. Yin, Y, Wang, ZY, Mora-Garcia, S, Li, J, Yoshida, S, Asami, T, Chory, J (2002) BES1 accumulates in the nucleus in response to brassinosteroids to regulate gene expression and promote stem elongation. Cell 109: pp. 181-191 CrossRef
  25. Wang, ZY, Nakano, T, Gendron, J, He, J, Chen, M, Vafeados, D, Yang, Y, Fujioka, S, Yoshida, S, Asami, T, Chory, J (2002) Nuclear-localized BZR1 mediates brassinosteroid-induced growth and feedback suppression of brassinosteroid biosynthesis. Dev Cell 2: pp. 505-513 CrossRef
  26. Yin, Y, Vafeados, D, Tao, Y, Yoshida, S, Asami, T, Chory, J (2005) A new class of transcription factors mediates brassinosteroid-regulated gene expression in Arabidopsis. Cell 120: pp. 249-259 11.044" target="_blank" title="It opens in new window">CrossRef
  27. Ye, H, Li, L, Guo, H, Yin, Y (2012) MYBL2 is a substrate of GSK3-like kinase BIN2 and acts as a corepressor of BES1 in brassinosteroid signaling pathway in Arabidopsis. Proc Natl Acad Sci U S A 109: pp. 20142-20147 CrossRef
  28. Gudesblat, GE, Schneider-Pizo艅, J, Betti, C, Mayerhofer, J, Vanhoutte, I, van Dongen, W, Boeren, S, Zhiponova, M, de Vries, S, Jonak, C, Russinova, E (2012) SPEECHLESS integrates brassinosteroid and stomata signalling pathways. Nat Cell Biol 14: pp. 548-554 CrossRef
  29. Poppenberger, B, Rozhon, W, Khan, M, Husar, S, Adam, G, Luschnig, C, Fujioka, S, Sieberer, T (2011) CESTA, a positive regulator of brassinosteroid biosynthesis. EMBO J 30: pp. 1149-1161 11.35" target="_blank" title="It opens in new window">CrossRef
  30. Kim, TW, Michniewicz, M, Bergmann, DC, Wang, ZY (2012) Brassinosteroid regulates stomatal development by GSK3-mediated inhibition of a MAPK pathway. Nature 482: pp. 419-422 CrossRef
  31. Khan, M, Rozhon, W, Bigeard, J, Pflieger, D, Husar, S, Pitzschke, A, Teige, M, Jonak, C, Hirt, H, Poppenberger, B (2013) Brassinosteroid-regulated GSK3/Shaggy-like kinases phosphorylate mitogen-activated protein (MAP) kinase kinases, which control stomata development in Arabidopsis thaliana. J Biol Chem 288: pp. 7519-7527 112.384453" target="_blank" title="It opens in new window">CrossRef
  32. Rozhon, W, Husar, S, Kalaivanan, F, Khan, M, Idlhammer, M, Shumilina, D, Lange, T, Hoffmann, T, Schwab, W, Fujioka, S, Poppenberger, B (2013) Genetic variation in plant CYP51s confers resistance against voriconazole, a novel inhibitor of brassinosteroid-dependent sterol biosynthesis. PLoS One 8: pp. e53650 CrossRef
  33. Min, YK, Asami, T, Fujioka, S, Murofushi, N, Yamaguchi, I, Yoshida, S (1999) New lead compounds for brassinosteroid biosynthesis inhibitors. Bioorg Med Chem Lett 9: pp. 425-430 CrossRef
  34. Sekimata, K, Han, SY, Yoneyama, K, Takeuchi, Y, Yoshida, S, Asami, T (2002) A specific and potent inhibitor of brassinosteroid biosynthesis possessing a dioxolane ring. J Agric Food Chem 50: pp. 3486-3490 11716w" target="_blank" title="It opens in new window">CrossRef
  35. Asami, T, Mizutani, M, Fujioka, S, Goda, H, Min, YK, Shimada, Y, Nakano, T, Takatsuto, S, Matsuyama, T, Nagata, N, Sakata, K, Yoshida, S (2001) Selective interaction of triazole derivatives with DWF4, a cytochrome P450 monooxygenase of the brassinosteroid biosynthetic pathway, correlates with brassinosteroid deficiency in planta. J Biol Chem 276: pp. 25687-25691 CrossRef
  36. Sekimata, K, Ohnishi, T, Mizutani, M, Todoroki, Y, Han, SY, Uzawa, J, Fujioka, S, Yoneyama, K, Takeuchi, Y, Takatsuto, S, Sakata, K, Yoshida, S, Asami, T (2008) Brz220 interacts with DWF4, a cytochrome P450 monooxygenase in brassinosteroid biosynthesis, and exerts biological activity. Biosci Biotechnol Biochem 72: pp. 7-12 CrossRef
  37. Tanaka, K, Asami, T, Yoshida, S, Nakamura, Y, Matsuo, T, Okamoto, S (2005) Brassinosteroid homeostasis in Arabidopsis is ensured by feedback expressions of multiple genes involved in its metabolism. Plant Physiol 138: pp. 1117-1125 1104/pp.104.058040" target="_blank" title="It opens in new window">CrossRef
  38. Kim, HB, Kwon, M, Ryu, H, Fujioka, S, Takatsuto, S, Yoshida, S, An, CS, Lee, I, Hwang, I, Choe, S (2006) The regulation of DWARF4 expression is likely a critical mechanism in maintaining the homeostasis of bioactive brassinosteroids in Arabidopsis. Plant Physiol 140: pp. 548-557 1104/pp.105.067918" target="_blank" title="It opens in new window">CrossRef
  39. Goda, H, Shimada, Y, Asami, T, Fujioka, S, Yoshida, S (2002) Microarray analysis of brassinosteroid-regulated genes in Arabidopsis. Plant Physiol 130: pp. 1319-1334 1104/pp.011254" target="_blank" title="It opens in new window">CrossRef
  40. Shi, YH, Zhu, SW, Mao, XZ, Feng, JX, Qin, YM, Zhang, L, Cheng, J, Wei, LP, Wang, ZY, Zhu, YX (2006) Transcriptome profiling, molecular biological, and physiological studies reveal a major role for ethylene in cotton fiber cell elongation. Plant Cell 18: pp. 651-664 1105/tpc.105.040303" target="_blank" title="It opens in new window">CrossRef
  41. Symons, GM, Davies, C, Shavrukov, Y, Dry, IB, Reid, JB, Thomas, MR (2006) Grapes on steroids. Brassinosteroids are involved in grape berry ripening. Plant Physiol 140: pp. 150-158 1104/pp.105.070706" target="_blank" title="It opens in new window">CrossRef
  42. Sekimata, K, Kimura, T, Kaneko, I, Nakano, T, Yoneyama, K, Takeuchi, Y, Yoshida, S, Asami, T (2001) A specific brassinosteroid biosynthesis inhibitor, Brz 2001: evaluation of its effects on Arabidopsis, cress, tobacco, and rice. Planta 213: pp. 716-721 CrossRef
  43. Hartwig, T, Corvalan, C, Best, NB, Budka, JS, Zhu, JY, Choe, S, Schulz, B (2012) Propiconazole is a specific and accessible brassinosteroid (BR) biosynthesis inhibitor for arabidopsis and maize. PLoS One 7: pp. e36625 CrossRef
  44. Oh, K, Yamada, K, Asami, T, Yoshizawa, Y (2012) Synthesis of novel brassinosteroid biosynthesis inhibitors based on the ketoconazole scaffold. Bioorg Med Chem Lett 22: pp. 1625-1628 11.12.120" target="_blank" title="It opens in new window">CrossRef
  45. Klein, PS, Melton, DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci U S A 93: pp. 8455-8459 CrossRef
  46. Stambolic, V, Ruel, L, Woodgett, JR (1996) Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol 6: pp. 1664-1668 CrossRef
  47. Yan, Z, Zhao, J, Peng, P, Chihara, RK, Li, J (2009) BIN2 functions redundantly with other Arabidopsis GSK3-like kinases to regulate brassinosteroid signaling. Plant Physiol 150: pp. 710-721 1104/pp.109.138099" target="_blank" title="It opens in new window">CrossRef
  48. Peng, P, Yan, Z, Zhu, Y, Li, J (2008) Regulation of the Arabidopsis GSK3-like kinase BRASSINOSTEROID-INSENSITIVE 2 through proteasome-mediated protein degradation. Mol Plant 1: pp. 338-346 CrossRef
  49. Zhang, S, Cai, Z, Wang, X (2009) The primary signaling outputs of brassinosteroids are regulated by abscisic acid signaling. Proc Natl Acad Sci U S A 106: pp. 4543-4548 CrossRef
  50. Bain, J, Plater, L, Elliott, M, Shpiro, N, Hastie, CJ, McLauchlan, H, Klevernic, I, Arthur, JS, Alessi, DR, Cohen, P (2007) The selectivity of protein kinase inhibitors: a further update. Biochem J 408: pp. 297-315 CrossRef
  51. Wallacea, A, Romneya, EM, Chaa, JW, Chaudhrya, FM (1977) Lithium toxicity in plants. Comm Soil Sci Plant Anal 8: pp. 773-780 CrossRef
  52. Naranjo, MA, Romero, C, Bell茅s, JM, Montesinos, C, Vicente, O, Serrano, R (2003) Lithium treatment induces a hypersensitive-like response in tobacco. Planta 217: pp. 417-424 CrossRef
  53. Zhu, JK, Liu, J, Xiong, L (1998) Genetic analysis of salt tolerance in arabidopsis. Evidence for a critical role of potassium nutrition. Plant Cell 10: pp. 1181-1191 1105/tpc.10.7.1181" target="_blank" title="It opens in new window">CrossRef
  54. De Rybel, B, Audenaert, D, Vert, G, Rozhon, W, Mayerhofer, J, Peelman, F, Coutuer, S, Denayer, T, Jansen, L, Nguyen, L, Vanhoutte, I, Beemster, GT, Vleminckx, K, Jonak, C, Chory, J, Inz茅, D, Russinova, E, Beeckman, T (2009) Chemical inhibition of a subset of Arabidopsis thaliana GSK3-like kinases activates brassinosteroid signaling. Chemistry & biology 16: pp. 594-604 CrossRef
  55. Clouse, SD, Langford, M, McMorris, TC (1996) A brassinosteroid-insensitive mutant in Arabidopsis thaliana exhibits multiple defects in growth and development. Plant Physiol 111: pp. 671-678 1104/pp.111.3.671" target="_blank" title="It opens in new window">CrossRef
  56. Fujioka, S, Li, J, Choi, YH, Seto, H, Takatsuto, S, Noguchi, T, Watanabe, T, Kuriyama, H, Yokota, T, Chory, J, Sakurai, A (1997) The Arabidopsis deetiolated2 mutant is blocked early in brassinosteroid biosynthesis. Plant Cell 9: pp. 1951-1962 1105/tpc.9.11.1951" target="_blank" title="It opens in new window">CrossRef
  57. Zhao, Y, Chow, TF, Puckrin, RS, Alfred, SE, Korir, AK, Larive, CK, Cutler, SR (2008) Chemical genetic interrogation of natural variation uncovers a molecule that is glycoactivated. Nat Chem Biol 3: pp. 716-721 CrossRef
  58. Knoop, F (1904) Der Abbau aromatischer Fetts盲uren im Tierk枚rper. Beitr Chem Physiol Pathol 6: pp. 150-162
  59. Spiess, GM, Zolman, BK (2013) Peroxisomes as a source of auxin signaling molecules. Subcell Biochem 69: pp. 257-281 CrossRef
  60. White, RH, Liebl, RA, Hymowitz, T (1990) Examination of 2,4-D tolerance in perennial Glycine species. Pest Biochem Physiol 38: pp. 153-161 CrossRef
  61. Davidonis, GH, Hamilton, RH, Mumma, RO (1980) Comparative metabolism of 2,4-dichlorophenoxyacetic acid in cotyledon and leaf callus from two varieties of soybean. Plant Physiol 65: pp. 94-97 1104/pp.65.1.94" target="_blank" title="It opens in new window">CrossRef
  62. Fujisawa, T, Matoba, Y, Katagi, T (2009) Application of separated leaf cell suspension to xenobiotic metabolism in plant. J Agric Food Chem 57: pp. 6982-6989 CrossRef
  63. Sinlapadech, T, Stout, J, Ruegger, MO, Deak, M, Chapple, C (2007) The hyper-fluorescent trichome phenotype of the brt1 mutant of Arabidopsis is the result of a defect in a sinapic acid:UDPG glucosyltransferase. Plant J 49: pp. 655-668 1111/j.1365-313X.2006.02984.x" target="_blank" title="It opens in new window">CrossRef
  64. Lehfeldt, C, Shirley, AM, Meyer, K, Ruegger, MO, Cusumano, JC, Viitanen, PV, Strack, D, Chapple, C (2000) Cloning of the SNG1 gene of Arabidopsis reveals a role for a serine carboxypeptidase-like protein as an acyltransferase in secondary metabolism. Plant Cell 12: pp. 1295-1306 1105/tpc.12.8.1295" target="_blank" title="It opens in new window">CrossRef
  65. Kim, HB, Schaller, H, Goh, CH, Kwon, M, Choe, S, An, CS, Durst, F, Feldmann, KA, Feyereisen, R (2005) Arabidopsis cyp51 mutant shows postembryonic seedling lethality associated with lack of membrane integrity. Plant Physiol 138: pp. 2033-2047 1104/pp.105.061598" target="_blank" title="It opens in new window">CrossRef
  66. Taiz, L, Zeiger, E (2006) Plant Physiology. Sinauer Associates, Inc, Sunderland, Massachusettes
  67. Kramer, EM, Bennett, MJ (2006) Auxin transport: a field in flux. Trends Plant Sci 11: pp. 382-386 CrossRef
  68. Korte, F, Kvesitadze, G, Ugrekhelidze, D, Gordeziani, M, Khatisashvili, G, Buadze, O, Zaalishvili, G, Coulston, F (2000) Organic toxicants and plants. Ecotoxicol Environ Saf 47: pp. 1-26 CrossRef
  
• 刊物主题：Plant Sciences; Agriculture; Tree Biology;
• 出版者：BioMed Central
• ISSN：1471-2229

文摘

Background Plant GSK-3/Shaggy-like kinases are key players in brassinosteroid (BR) signalling which impact on plant development and participate in response to wounding, pathogens and salt stress. Bikinin was previously identified in a chemical genetics screen as an inhibitor targeting these kinases. To dissect the structural elements crucial for inhibition of GSK-3/Shaggy-like kinases by bikinin and to isolate more potent compounds we synthesised a number of related substances and tested their inhibitory activity in vitro and in vivo using Arabidopsis thaliana. Results A pyridine ring with an amido succinic acid residue in position 2 and a halogen in position 5 were crucial for inhibitory activity. The compound with an iodine substituent in position 5, denoted iodobikinin, was most active in inhibiting BIN2 activity in vitro and efficiently induced brassinosteroid-like responses in vivo. Its methyl ester, methyliodobikinin, showed improved cell permeability, making it highly potent in vivo although it had lower activity in vitro. HPLC analysis revealed that the methyl residue was rapidly cleaved off in planta liberating active iodobikinin. In addition, we provide evidence that iodobikinin and bikinin are inactivated in planta by conjugation with glutamic acid or malic acid and that the latter process is catalysed by the malate transferase SNG1. Conclusion Brassinosteroids participate in regulation of many aspects of plant development and in responses to environmental cues. Thus compounds modulating their action are valuable tools to study such processes and may be an interesting opportunity to modify plant growth and performance in horticulture and agronomy. Here we report the development of bikinin derivatives with increased potency that can activate BR signalling and mimic BR action. Methyliodobikinin was 3.4 times more active in vivo than bikinin. The main reason for the superior activity of methyliodobikinin, the most potent compound, is its enhanced plant tissue permeability. Inactivation of bikinin and its derivatives in planta involves SNG1, which constitutes a novel pathway for modification of xenobiotic compounds.