Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Post-genomic illumination of paclitaxel biosynthesis

Nature Plants volume 10, pages 1875–1885 (2024)Cite this article

Subjects

Abstract

Paclitaxel rapidly became one of the most effective anticancer drugs. However, the production of paclitaxel is hindered by substantial challenges, particularly considering the significant quantities of drug required and the inherently low concentration of paclitaxel and its intermediates in plants. Paclitaxel is currently produced in a so-called semi-synthesis in which baccatin III is extracted from Taxus species and chemically converted to paclitaxel. Despite the fact that many of the intermediates of paclitaxel biosynthesis are yet to be experimentally determined, a set of recent papers—facilitated by the sequencing and assembly of three Taxus genomes—has uncovered the minimal gene sets for both baccatin III and paclitaxel biosynthesis. Here we summarize the key milestones towards our understanding of paclitaxel biosynthesis and highlight recent advancements made possible by genome-level analysis of potential key genes involved. We argue that these studies will ultimately pave the way towards the elucidation of the entire paclitaxel biosynthetic pathway and facilitate the industrial production of paclitaxel via synthetic biology approaches. However, several major challenges lie ahead before we can fully tap into the amazing curative potential that taxanes provide.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Timeline of the major events in paclitaxel research.
Fig. 2: The alternative routes of baccatin III biosynthesis.
Fig. 3: Oxetane ring formation.
Fig. 4: Genome assemblies facilitate our understanding of the paclitaxel biosynthesis pathway.

Similar content being viewed by others

References

  1. Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P. & McPhail, A. T. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 93, 2325–2327 (1971).

    PubMed  Google Scholar 

  2. Huang, C. H., Kingston, D. G., Magri, N. F., Samaranayake, G. & Boettner, F. E. New taxanes from Taxus brevifolia, 2. J. Nat. Prod. 49, 665–669 (1986).

    PubMed  Google Scholar 

  3. Yang, C.-P. H. & Horwitz, S. B. Taxol®: the first microtubule stabilizing agent. Int. J. Mol. Sci. 18, 1733 (2017).

    PubMed  PubMed Central  Google Scholar 

  4. Jordan, M. A. & Wilson, L. Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4, 253–265 (2004).

    PubMed  Google Scholar 

  5. Menzin, A. W., King, S. A., Aikins, J. K., Mikuta, J. J. & Rubin, S. C. Taxol (paclitaxel) was approved by FDA for the treatment of patients with recurrent ovarian cancer. Gynecol. Oncol. 54, 103 (1994).

    PubMed  Google Scholar 

  6. Zhang, Y., Scossa, F. & Fernie, A. R. The genomes of Taxus species unveil novel candidates in the biosynthesis of taxoids. Mol. Plant 14, 1773–1775 (2021).

    PubMed  Google Scholar 

  7. Bray, F. et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 74, 229–263 (2024).

    PubMed  Google Scholar 

  8. Li, J. et al. Chloroplastic metabolic engineering coupled with isoprenoid pool enhancement for committed taxanes biosynthesis in Nicotiana benthamiana. Nat. Commun. 10, 4850 (2019).

    PubMed  PubMed Central  Google Scholar 

  9. Nicolaou, K. et al. Total synthesis of taxol. Nature 367, 630–634 (1994).

    PubMed  Google Scholar 

  10. Min, L. et al. Strategies and lessons learned from total synthesis of taxol. Chem. Rev. 123, 4934–4971 (2023).

    PubMed  Google Scholar 

  11. Imamura, Y., Takaoka, K., Komori, Y., Nagatomo, M. & Inoue, M. Total synthesis of taxol enabled by inter‐and intramolecular radical coupling reactions. Angew. Chem. 135, e202219114 (2023).

    Google Scholar 

  12. Watanabe, T., Oga, K., Matoba, H., Nagatomo, M. & Inoue, M. Total synthesis of taxol enabled by intermolecular radical coupling and Pd-catalyzed cyclization. J. Am. Chem. Soc. 145, 25894–25902 (2023).

    PubMed  Google Scholar 

  13. Zhang, S. et al. Research advances in clinical applications, anticancer mechanism, total chemical synthesis, semi-synthesis and biosynthesis of paclitaxel. Molecules 28, 7517 (2023).

    PubMed  PubMed Central  Google Scholar 

  14. Mutanda, I., Li, J., Xu, F. & Wang, Y. Recent advances in metabolic engineering, protein engineering, and transcriptome-guided insights toward synthetic production of taxol. Front. Bioeng. Biotechnol. 9, 632269 (2021).

    PubMed  PubMed Central  Google Scholar 

  15. Cheng, J. et al. Chromosome-level genome of Himalayan yew provides insights into the origin and evolution of the paclitaxel biosynthetic pathway. Mol. Plant 14, 1199–1209 (2021).

    PubMed  Google Scholar 

  16. Xiong, X. et al. The Taxus genome provides insights into paclitaxel biosynthesis. Nat. Plants 7, 1026–1036 (2021).

    PubMed  PubMed Central  Google Scholar 

  17. Song, C. et al. Taxus yunnanensis genome offers insights into gymnosperm phylogeny and taxol production. Commun. Biol. 4, 1203 (2021).

    PubMed  PubMed Central  Google Scholar 

  18. Zhang, Y. et al. Synthetic biology identifies the minimal gene set required for paclitaxel biosynthesis in a plant chassis. Mol. Plant 16, 1951–1961 (2023).

    PubMed  Google Scholar 

  19. Jiang, B. et al. Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III. Science 383, 622–629 (2024).

    PubMed  Google Scholar 

  20. Liu, J. C.-T., De La Peña, R., Tocol, C. & Sattely, E. S. Reconstitution of early paclitaxel biosynthetic network. Nat. Commun. 15, 1419 (2024).

    PubMed  PubMed Central  Google Scholar 

  21. Yang, C. et al. Biosynthesis of the highly oxygenated tetracyclic core skeleton of Taxol. Nat. Commun. 15, 2339 (2024).

    PubMed  PubMed Central  Google Scholar 

  22. Zhao, Y. et al. Oxetane ring formation in taxol biosynthesis is catalyzed by a bifunctional cytochrome P450 enzyme. J. Am. Chem. Soc. 146, 801–810 (2023).

    PubMed  Google Scholar 

  23. Lange, B. M. & Conner, C. F. Taxanes and taxoids of the genus Taxus—a comprehensive inventory of chemical diversity. Phytochemistry 190, 112829 (2021).

    PubMed  PubMed Central  Google Scholar 

  24. Narayanan, A. K. & Nagegowda, D. A. Biosynthesis of the triterpenoid withanolides in Withania somnifera. Curr. Opin. Plant Biol. 81, 102576 (2024).

    PubMed  Google Scholar 

  25. Garza-Garcia, J. J. O. & Qu, Y. Chemical, pharmacological properties and biosynthesis of opioid mitragynine in Mitragyna speciosa (kratom). Curr. Opin. Plant Biol. 81, 102600 (2024).

    PubMed  Google Scholar 

  26. Chavez, B. G., Dias, S. L. & D’Auria, J. C. The evolution of tropane alkaloids: coca does it differently. Curr. Opin. Plant Biol. 81, 102606 (2024).

    PubMed  Google Scholar 

  27. Sánchez-Pérez, R. & Neilson, E. H. The case for sporadic cyanogenic glycoside evolution in plants. Curr. Opin. Plant Biol. 81, 102608 (2024).

    PubMed  Google Scholar 

  28. Bergman, M. E. & Dudareva, N. Plant specialized metabolism: diversity of terpene synthases and their products. Curr. Opin. Plant Biol. 81, 102607 (2024).

    PubMed  Google Scholar 

  29. Wani, M. C. & Horwitz, S. B. Nature as a remarkable chemist: a personal story of the discovery and development of Taxol. Anticancer Drugs 25, 482–487 (2014).

    PubMed  PubMed Central  Google Scholar 

  30. Walsh, V. & Goodman, J. From taxol to Taxol: the changing identities and ownership of an anti-cancer drug. Med. Anthropol. 21, 307–336 (2002).

    PubMed  Google Scholar 

  31. Guénard, D., Guéritte-Voegelein, F., Dubois, J. & Potier, P. Structure-activity relationships of Taxol and Taxotere analogues. J. Natl Cancer Inst. Monogr. 15, 79–82 (1993).

    Google Scholar 

  32. Holton, R., Biediger, R. J. & Boatman, D. P. in TAXOL®: Science and Applications (ed. Suffness, M.) Ch. 5 (CRC, 1995).

  33. Koepp, A. E. et al. Cyclization of geranylgeranyl diphosphate to taxa-4(5),11(12)-diene is the committed step of taxol biosynthesis in Pacific yew. J. Biol. Chem. 270, 8686–8690 (1995).

    PubMed  Google Scholar 

  34. Rohmer, M., Knani, M., Simonin, P., Sutter, B. & Sahm, H. Isoprenoid biosynthesis in bacteria: a novel pathway for the early steps leading to isopentenyl diphosphate. Biochem. J. 295, 517–524 (1993).

    PubMed  PubMed Central  Google Scholar 

  35. Rohmer, M., Seemann, M., Horbach, S., Bringer-Meyer, S. & Sahm, H. Glyceraldehyde 3-phosphate and pyruvate as precursors of isoprenic units in an alternative non-mevalonate pathway for terpenoid biosynthesis. J. Am. Chem. Soc. 118, 2564–2566 (1996).

    Google Scholar 

  36. Rodríguez-Concepción, M. & Boronat, A. Elucidation of the methylerythritol phosphate pathway for isoprenoid biosynthesis in bacteria and plastids: a metabolic milestone achieved through genomics. Plant Physiol. 130, 1079–1089 (2002).

    PubMed  Google Scholar 

  37. Guerra-Bubb, J., Croteau, R. & Williams, R. M. The early stages of taxol biosynthesis: an interim report on the synthesis and identification of early pathway metabolites. Nat. Prod. Rep. 29, 683–696 (2012).

    PubMed  PubMed Central  Google Scholar 

  38. Long, R. M., Lagisetti, C., Coates, R. M. & Croteau, R. B. Specificity of the N-benzoyl transferase responsible for the last step of Taxol biosynthesis. Arch. Biochem. Biophys. 477, 384–389 (2008).

    PubMed  PubMed Central  Google Scholar 

  39. Williams, D. C. et al. Intramolecular proton transfer in the cyclization of geranylgeranyl diphosphate to the taxadiene precursor of taxol catalyzed by recombinant taxadiene synthase. Chem. Biol. 7, 969–977 (2000).

    PubMed  Google Scholar 

  40. Wheeler, A. L. et al. Taxol biosynthesis: differential transformations of taxadien-5 alpha-ol and its acetate ester by cytochrome P450 hydroxylases from Taxus suspension cells. Arch. Biochem. Biophys. 390, 265–278 (2001).

    PubMed  Google Scholar 

  41. Jennewein, S., Long, R. M., Williams, R. M. & Croteau, R. Cytochrome p450 taxadiene 5alpha-hydroxylase, a mechanistically unusual monooxygenase catalyzing the first oxygenation step of taxol biosynthesis. Chem. Biol. 11, 379–387 (2004).

    PubMed  Google Scholar 

  42. Dejong, J. M. et al. Genetic engineering of taxol biosynthetic genes in Saccharomyces cerevisiae. Biotechnol. Bioeng. 93, 212–224 (2006).

    PubMed  Google Scholar 

  43. Li, H., Horiguchi, T., Croteau, R. & Williams, R. M. Studies on taxol biosynthesis: preparation of taxadiene-diol- and triol-derivatives by deoxygenation of taxusin. Tetrahedron 64, 6561–6567 (2008).

    PubMed  PubMed Central  Google Scholar 

  44. Jennewein, S., Rithner, C. D., Williams, R. M. & Croteau, R. B. Taxol biosynthesis: taxane 13 alpha-hydroxylase is a cytochrome P450-dependent monooxygenase. Proc. Natl Acad. Sci. USA 98, 13595–13600 (2001).

    PubMed  PubMed Central  Google Scholar 

  45. Kaspera, R. & Croteau, R. Cytochrome P450 oxygenases of Taxol biosynthesis. Phytochem. Rev. 5, 433–444 (2006).

    PubMed  PubMed Central  Google Scholar 

  46. Chau, M. & Croteau, R. Molecular cloning and characterization of a cytochrome P450 taxoid 2alpha-hydroxylase involved in Taxol biosynthesis. Arch. Biochem. Biophys. 427, 48–57 (2004).

    PubMed  Google Scholar 

  47. Walker, K., Long, R. & Croteau, R. The final acylation step in taxol biosynthesis: cloning of the taxoid C13-side-chain N-benzoyltransferase from Taxus. Proc. Natl Acad. Sci. USA 99, 9166–9171 (2002).

    PubMed  PubMed Central  Google Scholar 

  48. Walker, K. & Croteau, R. Taxol biosynthetic genes. Phytochemistry 58, 1–7 (2001).

    PubMed  Google Scholar 

  49. Walker, K. D., Klettke, K., Akiyama, T. & Croteau, R. Cloning, heterologous expression, and characterization of a phenylalanine aminomutase involved in Taxol biosynthesis. J. Biol. Chem. 279, 53947–53954 (2004).

    PubMed  Google Scholar 

  50. Eisenreich, W., Menhard, B., Hylands, P. J., Zenk, M. H. & Bacher, A. Studies on the biosynthesis of taxol: the taxane carbon skeleton is not of mevalonoid origin. Proc. Natl Acad. Sci. USA 93, 6431–6436 (1996).

    PubMed  PubMed Central  Google Scholar 

  51. Ketchum, R. E. et al. Taxus metabolomics: methyl jasmonate preferentially induces production of taxoids oxygenated at C-13 in Taxus × media cell cultures. Phytochemistry 62, 901–909 (2003).

    PubMed  Google Scholar 

  52. Sanchez-Muñoz, R. et al. A novel hydroxylation step in the taxane biosynthetic pathway: a new approach to paclitaxel production by synthetic biology. Front. Bioeng. Biotechnol. 8, 410 (2020).

    PubMed  PubMed Central  Google Scholar 

  53. Sabzehzari, M., Zeinali, M. & Naghavi, M. R. Alternative sources and metabolic engineering of Taxol: advances and future perspectives. Biotechnol. Adv. 43, 107569 (2020).

    PubMed  Google Scholar 

  54. Ajikumar, P. K. et al. Isoprenoid pathway optimization for Taxol precursor overproduction in Escherichia coli. Science 330, 70–74 (2010).

    PubMed  PubMed Central  Google Scholar 

  55. Huang, Q., Roessner, C. A., Croteau, R. & Scott, A. I. Engineering Escherichia coli for the synthesis of taxadiene, a key intermediate in the biosynthesis of taxol. Bioorg. Med. Chem. 9, 2237–2242 (2001).

    PubMed  Google Scholar 

  56. Engels, B., Dahm, P. & Jennewein, S. Metabolic engineering of taxadiene biosynthesis in yeast as a first step towards Taxol (Paclitaxel) production. Metab. Eng. 10, 201–206 (2008).

    PubMed  Google Scholar 

  57. Besumbes, O. et al. Metabolic engineering of isoprenoid biosynthesis in Arabidopsis for the production of taxadiene, the first committed precursor of Taxol. Biotechnol. Bioeng. 88, 168–175 (2004).

    PubMed  Google Scholar 

  58. Hasan, M. M. et al. Metabolic engineering of Nicotiana benthamiana for the increased production of taxadiene. Plant Cell Rep. 33, 895–904 (2014).

    PubMed  Google Scholar 

  59. De La Peña, R. & Sattely, E. S. Rerouting plant terpene biosynthesis enables momilactone pathway elucidation. Nat. Chem. Biol. 17, 205–212 (2021).

    PubMed  Google Scholar 

  60. Utomo, J. C., Chaves, F. C., Bauchart, P., Martin, V. J. J. & Ro, D. K. Developing a yeast platform strain for an enhanced taxadiene biosynthesis by CRISPR/Cas9. Metabolites 11, 147 (2021).

    PubMed  PubMed Central  Google Scholar 

  61. Rontein, D. et al. CYP725A4 from yew catalyzes complex structural rearrangement of taxa-4(5),11(12)-diene into the cyclic ether 5(12)-oxa-3(11)-cyclotaxane. J. Biol. Chem. 283, 6067–6075 (2008).

    PubMed  Google Scholar 

  62. Edgar, S. et al. Mechanistic insights into taxadiene epoxidation by taxadiene-5α-hydroxylase. ACS Chem. Biol. 11, 460–469 (2016).

    PubMed  Google Scholar 

  63. Li, C. et al. A cytochrome P450 enzyme catalyses oxetane ring formation in paclitaxel biosynthesis. Angew. Chem. Int. Ed. 63, e202407070 (2024).

    Google Scholar 

  64. Schoendorf, A., Rithner, C. D., Williams, R. M. & Croteau, R. B. Molecular cloning of a cytochrome P450 taxane 10β-hydroxylase cDNA from Taxus and functional expression in yeast. Proc. Natl Acad. Sci. USA 98, 1501–1506 (2001).

    PubMed  PubMed Central  Google Scholar 

  65. Chau, M., Walker, K., Long, R. & Croteau, R. Regioselectivity of taxoid-O-acetyltransferases: heterologous expression and characterization of a new taxadien-5alpha-ol-O-acetyltransferase. Arch. Biochem. Biophys. 430, 237–246 (2004).

    PubMed  Google Scholar 

  66. Hampel, D., Mau, C. J. & Croteau, R. B. Taxol biosynthesis: identification and characterization of two acetyl CoA:taxoid-O-acetyl transferases that divert pathway flux away from Taxol production. Arch. Biochem. Biophys. 487, 91–97 (2009).

    PubMed  PubMed Central  Google Scholar 

  67. Li, B. J. et al. Improving 10-deacetylbaccatin III-10-β-O-acetyltransferase catalytic fitness for Taxol production. Nat. Commun. 8, 15544 (2017).

    PubMed  PubMed Central  Google Scholar 

  68. Ondari, M. E. & Walker, K. D. The taxol pathway 10-O-acetyltransferase shows regioselective promiscuity with the oxetane hydroxyl of 4-deacetyltaxanes. J. Am. Chem. Soc. 130, 17187–17194 (2008).

    PubMed  Google Scholar 

  69. Lanier, E. R., Andersen, T. B. & Hamberger, B. Plant terpene specialized metabolism: complex networks or simple linear pathways? Plant J. 114, 1178–1201 (2023).

    PubMed  PubMed Central  Google Scholar 

  70. Xie, L., Gao, J. & Zhou, Y. J. Synthetic biology for Taxol biosynthesis and sustainable production. Trends Biotechnol. 42, 674–676 (2024).

    PubMed  Google Scholar 

  71. Ramírez‐Estrada, K. et al. Transcript profiling of jasmonate‐elicited Taxus cells reveals a β‐phenylalanine‐CoA ligase. Plant Biotechnol. J. 14, 85–96 (2016).

    PubMed  Google Scholar 

  72. Koetsier, M. J., Jekel, P. A., Wijma, H. J., Bovenberg, R. A. & Janssen, D. B. Aminoacyl-coenzyme A synthesis catalyzed by a CoA ligase from Penicillium chrysogenum. FEBS Lett. 585, 893–898 (2011).

    PubMed  Google Scholar 

  73. Gou, Y., Jiang, X. & Lian, J. Intricate metabolic network for paclitaxel biosynthesis. BioDes. Res. https://doi.org/10.34133/bdr.0035 (2024).

  74. Liu, X., Zhu, X., Cheng, J. & Jiang, H. A new era for paclitaxel biosynthesis is coming. Mol. Plant 17, 370–371 (2024).

    PubMed  Google Scholar 

  75. Cope, E. A. Taxaceae: the genera and cultivated species. Bot. Rev. 64, 291–322 (1998).

    Google Scholar 

  76. Bundy, J. G., Davey, M. P. & Viant, M. R. Environmental metabolomics: a critical review and future perspectives. Metabolomics 5, 3–21 (2009).

    Google Scholar 

  77. Srividya, N. et al. Biochemical characterization of acyl activating enzymes for side chain moieties of Taxol and its analogs. J. Biol. Chem. 295, 4963–4973 (2020).

    PubMed  PubMed Central  Google Scholar 

  78. Nevarez, D. M., Mengistu, Y. A., Nawarathne, I. N. & Walker, K. D. An N-aroyltransferase of the BAHD superfamily has broad aroyl CoA specificity in vitro with analogues of N-dearoylpaclitaxel. J. Am. Chem. Soc. 131, 5994–6002 (2009).

    PubMed  Google Scholar 

  79. Chen, X. Y., Wang, J. Q., Yang, Y., Li, J. & Chen, Z. S. Natural product as substrates of ABC transporters: a review. Recent Pat. Anticancer Drug Discov. 16, 222–238 (2021).

    PubMed  Google Scholar 

  80. Wang, J. Q. et al. Multidrug resistance proteins (MRPs): structure, function and the overcoming of cancer multidrug resistance. Drug Resist. Updat. 54, 100743 (2021).

    PubMed  Google Scholar 

  81. Syed, S. B. et al. Targeting P-glycoprotein: investigation of piperine analogs for overcoming drug resistance in cancer. Sci. Rep. 7, 7972 (2017).

    PubMed  PubMed Central  Google Scholar 

  82. Yu, C. et al. Integrated mass spectrometry imaging and single-cell transcriptome atlas strategies provide novel insights into taxoid biosynthesis and transport in Taxus mairei stems. Plant J. 115, 1243–1260 (2023).

    PubMed  Google Scholar 

  83. Zheng, H. et al. Transcriptional regulatory network of high-value active ingredients in medicinal plants. Trends Plant Sci. 28, 429–446 (2023).

    PubMed  Google Scholar 

  84. Ying, C. et al. miR5298b regulated taxol biosynthesis by acting on TcNPR3, resulting in an alleviation of the strong inhibition of the TcNPR3–TcTGA6 complex in Taxus chinensis. Int. J. Biol. Macromol. 248, 125909 (2023).

    PubMed  Google Scholar 

  85. Zhang, M. et al. Transcriptome-wide identification and screening of WRKY factors involved in the regulation of taxol biosynthesis in Taxus chinensis. Sci. Rep. 8, 5197 (2018).

    PubMed  PubMed Central  Google Scholar 

  86. Zhang, K. et al. Transcriptome-wide analysis of AP2/ERF transcription factors involved in regulating Taxol biosynthesis in Taxus × media. Ind. Crops Prod. 171, 113972 (2021).

    Google Scholar 

  87. Zhan, X. et al. Mass spectrometry imaging and single-cell transcriptional profiling reveal the tissue-specific regulation of bioactive ingredient biosynthesis in Taxus leaves. Plant Commun. 4, 100630 (2023).

    PubMed  PubMed Central  Google Scholar 

  88. Chen, Y., Wang, Y., Liang, X., Zhang, Y. & Fernie, A. R. Mass spectrometric exploration of phytohormone profiles and signaling networks. Trends Plant Sci. https://doi.org/10.1016/j.tplants.2022.12.006 (2023).

  89. Shen, S. et al. An Oryza-specific hydroxycinnamoyl tyramine gene cluster contributes to enhanced disease resistance. Sci. Bull. 66, 2369–2380 (2021).

    Google Scholar 

  90. Chakraborty, P. Gene cluster from plant to microbes: their role in genome architecture, organism’s development, specialized metabolism and drug discovery. Biochimie 193, 1–15 (2022).

    PubMed  Google Scholar 

  91. Nützmann, H. W. & Osbourn, A. Gene clustering in plant specialized metabolism. Curr. Opin. Biotechnol. 26, 91–99 (2014).

    PubMed  Google Scholar 

  92. Zhan, C. et al. Plant metabolic gene clusters in the multi-omics era. Trends Plant Sci. 27, 981–1001 (2022).

    PubMed  Google Scholar 

  93. Boycheva, S., Daviet, L., Wolfender, J. L. & Fitzpatrick, T. B. The rise of operon-like gene clusters in plants. Trends Plant Sci. 19, 447–459 (2014).

    PubMed  Google Scholar 

  94. Nützmann, H. W., Scazzocchio, C. & Osbourn, A. Metabolic gene clusters in eukaryotes. Annu. Rev. Genet. 52, 159–183 (2018).

    PubMed  Google Scholar 

  95. Rhee, S. Y. & Mutwil, M. Towards revealing the functions of all genes in plants. Trends Plant Sci. 19, 212–221 (2014).

    PubMed  Google Scholar 

  96. Purugganan, M. D. & Jackson, S. A. Advancing crop genomics from lab to field. Nat. Genet. 53, 595–601 (2021).

    PubMed  Google Scholar 

  97. Stitt, M. Systems-integration of plant metabolism: means, motive and opportunity. Curr. Opin. Plant Biol. 16, 381–388 (2013).

    PubMed  Google Scholar 

  98. Usadel, B. et al. Co-expression tools for plant biology: opportunities for hypothesis generation and caveats. Plant Cell Environ. 32, 1633–1651 (2009).

    PubMed  Google Scholar 

  99. Patil, R. A., Kolewe, M. E., Normanly, J., Walker, E. L. & Roberts, S. C. Contribution of taxane biosynthetic pathway gene expression to observed variability in paclitaxel accumulation in Taxus suspension cultures. Biotechnol. J. 7, 418–427 (2012).

    PubMed  PubMed Central  Google Scholar 

  100. Li, S. T. et al. Transcriptional profile of Taxus chinensis cells in response to methyl jasmonate. BMC Genomics 13, 295 (2012).

    PubMed  PubMed Central  Google Scholar 

  101. Hong, B. et al. Biosynthesis of strychnine. Nature 607, 617–622 (2022).

    PubMed  PubMed Central  Google Scholar 

  102. Nett, R. S. et al. Plant carbonic anhydrase-like enzymes in neuroactive alkaloid biosynthesis. Nature 624, 182–191 (2023).

    PubMed  PubMed Central  Google Scholar 

  103. Liu, F., Fernie, A. R. & Zhang, Y. Plant gene co-expression defines the biosynthetic pathway of neuroactive alkaloids. Mol. Plant 17, 372–374 (2024).

    PubMed  Google Scholar 

Download references

Acknowledgements

F.L. and Y.Z. thank the National Natural Science Foundation of China (grant no. 32470416) for supporting this work.

Author information

Author notes

  1. These authors contributed equally: Alisdair R. Fernie, Fang Liu.

Authors and Affiliations

  1. Max Planck Institute of Molecular Plant Physiology, Potsdam-Golm, Germany

    Alisdair R. Fernie

  2. Key Laboratory of Seed Innovation, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China

    Fang Liu & Youjun Zhang

  3. College of Advanced Agricultural Sciences, University of Chinese Academy of Sciences, Beijing, China

    Youjun Zhang

Authors
  1. Alisdair R. Fernie
    View author publications

    Search author on:PubMed Google Scholar

  2. Fang Liu
    View author publications

    Search author on:PubMed Google Scholar

  3. Youjun Zhang
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Y.Z. and A.R.F. jointly developed the logic and framework, conducted the literature review and led the overall writing process. F.L. summarized the main contents for each section, analysed the data and schematically summarized them into individual figures.

Corresponding authors

Correspondence to Alisdair R. Fernie or Youjun Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Plants thanks Zhihua Zhou and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

Supplementary Fig. 1.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fernie, A.R., Liu, F. & Zhang, Y. Post-genomic illumination of paclitaxel biosynthesis. Nat. Plants 10, 1875–1885 (2024). https://doi.org/10.1038/s41477-024-01869-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41477-024-01869-8

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing