The target genes for Solanaceae secondary metabolism engineering: evolution and genome organization

Metabolic engineering of plant secondary metabolism provides a way to obtain plants with elevated level of valuable molecular compounds. Alternatively, metabolic engineering can be used for reduction of toxic substances accumulation in plant tissues. This approach allows one to expand the application of toxic plants in agriculture and biotechnology. The crops of Solanaceae family provide an example of toxic plants of high economic value. Solanaceae family includes edible crops such as potato, tomato and eggplants, medicinal plants like Withania somnifera L. and major non-food crop Nicotiana tabacum L. The secondary metabolism of Solanaceae family is widely diverse and includes the biosynthesis and accumulation of number of toxic compounds, such as nicotine and other alkaloids in tobacco, steroidal glycoalcaloids in potato and withanolides in winter cherry W. somnifera. The secondary metabolic pathways of Solanaceae family have evolved from primary metabolism via duplication of the enzyme coding genes and diversification of genes functions. Local, segment and the whole genome duplications and subsequent formation of metabolic genes clusters are the main processes in secondary metabolic pathways formation. Recent whole genome sequence data from number of Sonanaceae species allows one to reconstruct the putative mechanism of primary and secondary metabolism genetic control and evolution. Genomic data together with novel guided endonuclease based genome modification tools provide an opportunity for introduction of precise changes into secondary metabolism. Suppression of nicotine accumulation in tobacco is promising approach for developing of novel plant systems for molecular farming. Toxicity of wild potato relatives impedes their usage in potato breeding. Tobacco and wild potato toxicity reduction can be achieved by different genome modification approaches: knock-out of the key enzyme genes of alkaloids synthesis, the large deletion of the whole cluster of the secondary metabolic genes or the precise editing of key transcription factors in secondary metabolism regulation pathways.

1. Abdelkareem A. et al. Jasmonate-induced biosynthesis of steroidal glycoalkaloids depends on COI1 proteins in tomato // Biochemical and Biophysical Research Communications. 2017. Vol. 489, № 2. P. 206–210.

2. Aharoni A., Galili G. Metabolic engineering of the plant primary–secondary metabolism interface // Current Opinion in Biotechnology. 2011. Vol. 22, № 2. P. 239–244. DOI: 10.1016/j.copbio.2010.11.004

3. Aversano R. et al. The Solanum commersonii Genome Sequence Provides Insights into Adaptation to Stress Conditions and Genome Evolution of Wild Potato Relatives // The Plant Cell. 2015. Vol. 27, № 4. P. 954–968. DOI: 10.1105/tpc.114.135954

4. Beekwilder J. et al. Characterization of potato proteinase inhibitor II reactive site mutants // Eur. J. Biochem. 2000. Vol. 267, № 7. P. 1975–1984.

5. Boer K.D. et al. APETALA2/ETHYLENE RESPONSE FACTOR and basic helix–loop–helix tobacco transcription factors cooperatively mediate jasmonate-elicited nicotine biosynthesis // The Plant Journal. 2011. Vol. 66, № 6. P. 1053–1065. DOI: 10.1111/j.1365-313X.2011.04566.x

6. Bombarely A. et al. Insight into the evolution of the Solanaceae from the parental genomes of Petunia hybrida // Nature Plants. 2016. Vol. 2, № 6. P. 16074. DOI: 10.1038/nplants.2016.74

7. Cárdenas P.D. et al. GAME9 regulates the biosynthesis of steroidal alkaloids and upstream isoprenoids in the plant mevalonate pathway // Nat Commun. 2016. Vol. 7. P. 10654. DOI: 10.1038/ncomms10654

8. Chae L. et al. Genomic Signatures of Specialized Metabolism in Plants // Science. 2014. Vol. 344, № 6183. P. 510–513. DOI: 10.1126/science.1252076

9. Chintapakorn Y., Hamill J.D. Antisense-mediated down-regulation of putrescine N-methyltransferase activity in transgenic Nicotiana tabacum L. can lead to elevated levels of anatabine at the expense of nicotine // Plant Mol. Biol. 2003. Vol. 53, № 1–2. P. 87–105. DOI: 10.1023/B:PLAN.0000009268.45851.95

10. Chu H.Y., Wegel E., Osbourn A. From hormones to secondary metabolism: the emergence of metabolic gene clusters in plants // The Plant Journal. 2011. Vol. 66, № 1. P. 66–79. DOI: 10.1111/j.1365-313X.2011.04503.x

11. D’Amelia V. et al. Subfunctionalization of duplicate MYB genes in Solanum commersonii generated the cold-induced ScAN2 and the anthocyanin regulator ScAN1 // Plant Cell Environ. 2018. Vol. 41, № 5. P. 1038–1051. DOI: 10.1111/pce.12966

12. Deboer K.D. et al. The A622 gene in Nicotiana glauca (tree tobacco): evidence for a functional role in pyridine alkaloid synthesis // Plant Mol. Biol. 2009. Vol. 69, № 3. P. 299–312. DOI: 10.1007/s11103-008-9425-2

13. Field B. et al. Formation of plant metabolic gene clusters within dynamic chromosomal regions // PNAS. 2011. Vol. 108, № 38. P. 16116– 16121. DOI: 10.1073/pnas.1109273108

14. Freeling M., Thomas B.C. Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity // Genome Res. 2006. Vol. 16, № 7. P. 805–814. DOI: 10.1101/gr.3681406

15. Gerasimova S.V. et al. Genome editing system CRISPR/CAS9 and peculiarities of its application in monocots // Russ J Plant Physiol. 2017. Vol. 64, № 2. P. 141–155. DOI: 10.1134/S1021443717010071

16. Goossens J. et al. Jasmonates: signal transduction components and their roles in environmental stress responses // Plant Mol Biol. 2016. Vol. 91, № 6. P. 673–689. DOI: 10.1007/s11103-016-0480-9

17. Hardigan M.A. et al. Genome diversity of tuber-bearing Solanum uncovers complex evolutionary history and targets of domestication in the cultivated potato // PNAS. 2017. Vol. 114, № 46. P. E9999– E10008. DOI: 10.1073/pnas.1714380114

18. Heim W.G. et al. Cloning and characterization of a Nicotiana tabacum methylputrescine oxidase transcript // Phytochemistry. 2007. Vol. 68, № 4. P. 454–463. DOI: 10.1016/j.phytochem.2006.11.003

19. Hibi N. et al. Gene expression in tobacco low-nicotine mutants // Plant Cell. 1994. Vol. 6, № 5. P. 723–735. DOI: 10.1105/tpc.6.5.723

20. Ivanova K.A., Gerasimova S.V., Khlestkina E.K. The Biosynthesis Regulation of Potato Steroidal Glycoalkaloids // Vavilov Journal of Genetics and Breeding. 2018. Vol. 22, № 1. P. 25–34. DOI: 10.18699/VJ18.328

21. Kajikawa M. et al. Genomic Insights into the Evolution of the Nicotine Biosynthesis Pathway in Tobacco // Plant Physiol. 2017. Vol. 174, № 2. P. 999–1011. DOI: 10.18699/VJ18.328

22. Kajikawa M. et al. Vacuole-Localized Berberine Bridge Enzyme-Like Proteins Are Required for a Late Step of Nicotine Biosynthesis in Tobacco1[C][W] // Plant Physiol. 2011. Vol. 155, № 4. P. 2010–2022. DOI: 10.1104/pp.110.170878

23. Kajikawa M., Hirai N., Hashimoto T. A PIP-family protein is required for biosynthesis of tobacco alkaloids // Plant Mol. Biol. 2009. Vol. 69, № 3. P. 287–298. DOI: 10.1007/s11103-008-9424-3

24. Knoch E. et al. Third DWF1 paralog in Solanaceae, sterol Δ24-isomerase, branches withanolide biosynthesis from the general phytosterol pathway // PNAS. 2018. P. 201807482. DOI: 10.1073/pnas.1807482115

25. Korotkova A.M. et al. Crop genes modified using the CRISPR/Cas system // Russ J Genet Appl Res. 2017. Vol. 7, № 8. P. 822–832. DOI: 10.1134/S2079059717050124

26. Kumar A. et al. Lanosterol synthase-like is involved with differential accumulation of steroidal glycoalkaloids in potato // Planta. 2017. Vol. 246, № 6. P. 1189–1202. DOI: 10.1007/s00425-017-2763-z

27. Lewis R.S. et al. Transgenic and Mutation-Based Suppression of a Berberine Bridge Enzyme-Like (BBL) Gene Family Reduces Alkaloid Content in Field-Grown Tobacco // PLOS ONE. 2015. Vol. 10, № 2. P. e0117273. DOI:10.1371/journal.pone.0117273

28. Li Y. et al. Genomic Analyses Yield Markers for Identifying Agronomically Important Genes in Potato // Molecular Plant. 2018. Vol. 11, № 3. P. 473–484. DOI: 10.1016/j.molp.2018.01.009

29. Markova D.N. et al. Evolutionary history of two pollen self-incompatibility factors reveals alternate routes to self-compatibility within Solanum // Am. J. Bot. 2017. Vol. 104, № 12. P. 1904–1919. DOI: 10.3732/ajb.1700196

30. Matsuura H.N., Fett-Neto A.G. Plant alkaloids: main features, toxicity, and mechanisms of action //Plant Toxins. – Springer, Dordrecht. 2017. – P. 243-261. DOI 10.1007/978-94-007-6728-7_2-1

31. McCue K.F. et al. Modification of potato steroidal glycoalkaloids with silencing RNA constructs // Am. J. Potato Res. 2018. Vol. 95, №1. P. 9-14. DOI: 10.1007/s12230-017-9609-x

32. McCue K.F. et al. Potato glycosterol rhamnosyltransferase, the terminal step in triose side-chain biosynthesis // Phytochemistry. 2007. Vol. 68, № 3. P. 327–334. DOI: 10.1016/j.phytochem.2006.10.025

33. McCue K.F. et al. The primary in vivo steroidal alkaloid glucosyltransferase from potato // Phytochemistry. 2006. Vol. 67, № 15. P. 1590–1597. DOI: 10.1016/j.phytochem.2005.09.037

34. McCue K.F. Potato glycoalkaloids, past present and future. Fruit Veget. Cereal Sci. Biotechn. 2009. Vol. 3, №1. P. 65-71.

35. Mishra L.C., Singh B.B., Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review // Altern Med Rev. 2000. Vol. 5, № 4. P. 334–346.

36. Moghe G.D. et al. Consequences of Whole-Genome Triplication as Revealed by Comparative Genomic Analyses of the Wild Radish Raphanus raphanistrum and Three Other Brassicaceae Species // The Plant Cell. 2014. Vol. 26, № 5. P. 1925–1937. DOI: 10.1105/tpc.114.124297

37. Moghe G.D., Last R.L. Something Old, Something New: Conserved Enzymes and the Evolution of Novelty in Plant Specialized Metabolism // Plant Physiology. 2015. Vol. 169, № 3. P. 1512–1523. DOI: 10.1104/pp.15.00994

38. Nagy R. et al. The characterization of novel mycorrhiza-specific phosphate transporters from Lycopersicon esculentum and Solanum tuberosum uncovers functional redundancy in symbiotic phosphate transport in solanaceous species // Plant J. 2005. Vol. 42, № 2. P. 236–250. DOI: 10.1111/j.1365-313X.2005.02364.x

39. Nakayasu M. et al. A Dioxygenase Catalyzes Steroid 16α-Hydroxylation in Steroidal Glycoalkaloid Biosynthesis1 // Plant Physiol. 2017. Vol. 175, № 1. P. 120–133. DOI: 10.1104/pp.17.00501

40. Nützmann H.-W., Osbourn A. Gene clustering in plant specialized metabolism // Current Opinion in Biotechnology. 2014. Vol. 26. P. 91– 99. DOI: 10.1016/j.copbio.2013.10.009

41. Ober D. Seeing double: gene duplication and diversification in plant secondary metabolism // Trends Plant Sci. 2005. Vol. 10, № 9. P. 444–449. DOI: 10.1016/j.tplants.2005.07.007

42. Osbourn A. Secondary metabolic gene clusters: evolutionary toolkits for chemical innovation // Trends in Genetics. 2010. Vol. 26, № 10. P. 449–457. DOI: 10.1016/j.tig.2010.07.001

43. Patra B. et al. Transcriptional regulation of secondary metabolite biosynthesis in plants // Biochim. Biophys. Acta. 2013. Vol. 1829, № 11. P. 1236–1247. DOI: 10.1016/j.bbagrm.2013.09.006

44. Qin C. et al. Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization // PNAS. 2014. Vol. 111, № 14. P. 5135–5140. DOI: 10.1073/pnas.1400975111

45. Riechers D.E., Timko M.P. Structure and expression of the gene family encoding putrescine N-methyltransferase in Nicotiana tabacum: new clues to the evolutionary origin of cultivated tobacco // Plant Mol. Biol. 1999. Vol. 41, № 3. P. 387–401.

46. Schläpfer P. et al. Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants // Plant Physiol. 2017. Vol. 173, № 4. P. 2041–2059. DOI: 10.1104/pp.16.01942

47. Schranz M.E., Mohammadin S., Edger P.P. Ancient whole genome duplications, novelty and diversification: the WGD Radiation LagTime Model // Curr. Opin. Plant Biol. 2012. Vol. 15, № 2. P. 147–153. DOI: 10.1016/j.pbi.2012.03.011

48. Shoji T., Hashimoto T. Tobacco MYC2 Regulates Jasmonate-Inducible Nicotine Biosynthesis Genes Directly and By Way of the NIC2-Locus ERF Genes // Plant Cell Physiol. 2011. Vol. 52, № 6. P. 1117–1130. DOI: 10.1093/pcp/pcr063

49. Shoji T., Hashimoto T. Why does anatabine, but not nicotine, accumulate in jasmonate-elicited cultured tobacco BY-2 cells? // Plant Cell Physiol. 2008. Vol. 49, № 8. P. 1209–1216. DOI: 10.1093/pcp/pcn096

50. Sonawane P.D. et al. Plant cholesterol biosynthetic pathway overlaps with phytosterol metabolism // Nat Plants. 2016. Vol. 3. P. 16205. DOI: 10.1038/nplants.2016.205

51. The Tomato Genome Consortium. The tomato genome sequence provides insights into fleshy fruit evolution // Nature. 2012. Vol. 485, № 7400. P. 635–641. DOI: 10.1038/nature11119

52. Töpfer N., Fuchs L.-M., Aharoni A. The PhytoClust tool for metabolic gene clusters discovery in plant genomes // Nucleic Acids Res. 2017. Vol. 45, № 12. P. 7049–7063. DOI: 10.1093/nar/gkx404

53. Umemoto N. et al. Two Cytochrome P450 Monooxygenases Catalyze Early Hydroxylation Steps in the Potato Steroid Glycoalkaloid Biosynthetic Pathway // Plant Physiol. 2016. Vol. 171, № 4. P. 2458–2467. DOI 10.1104/pp.16.00137.

54. Wang P. et al. Generation of tobacco lines with widely different reduction in nicotine levels via RNA silencing approaches // J. Biosci. 2008. Vol. 33, № 2. P. 177–184.

55. Wang P. et al. Silencing of PMT expression caused a surge of anatabine accumulation in tobacco // Mol. Biol. Rep. 2009. Vol. 36, № 8. P. 2285–2289. DOI: 10.1007/s11033-009-9446-1

56. Xie J. et al. Biotechnology: A tool for reduced risk tobacco products - The nicotine experience from test tube to cigarette pack // Rev Adv Tob Sci. 2004. Vol. 30. P. 17–37.

57. Xu S. et al. Wild tobacco genomes reveal the evolution of nicotine biosynthesis // Proceedings of the National Academy of Sciences. 2017. Vol. 114, № 23. P. 6133–6138. DOI: 10.1073/pnas.1700073114

58. Zhang H.-B. et al. Tobacco Transcription Factors NtMYC2a and NtMYC2b Form Nuclear Complexes with the NtJAZ1 Repressor and Regulate Multiple Jasmonate-Inducible Steps in Nicotine Biosynthesis // Molecular Plant. 2012. Vol. 5, № 1. P. 73–84. DOI: 10.1093/mp/ssr056

59. Zhang S. et al. Distinct subfunctionalization and neofunctionalization of the B-class MADS-box genes in Physalis floridana // Planta. 2015. Vol. 241, № 2. P. 387–402. DOI: 10.1007/s00425-014-2190-3

60. Zhou M., Memelink J. Jasmonate-responsive transcription factors regulating plant secondary metabolism // Biotechnology Advances. 2016. Vol. 34, № 4. P. 441–449. DOI: 10.1016/j.biotechadv.2016.02.004

61. Zhu G. et al. Rewiring of the Fruit Metabolome in Tomato Breeding // Cell. 2018. Vol. 172, № 1–2. P. 249-261.e12. DOI: 10.1016/j.cell.2017.12.019