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    University - Student Department: Chemistry Position: Graduate

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  • Mail Code: 5080

All Publications

  • Plants Utilize a Protection/Deprotection Strategy in Limonoid Biosynthesis: A "Missing Link" Carboxylesterase Boosts Yields and Provides Insights into Furan Formation. Journal of the American Chemical Society Hodgson, H., Stephenson, M. J., Kikuchi, S., Martin, L. B., Liu, J. C., Casson, R., Rejzek, M., Sattely, E. S., Osbourn, A. 2024

    Abstract

    The furan ring is a defining feature of limonoids, a class of highly rearranged and bioactive plant tetranortriterpenoids. We recently reported an apparent complete biosynthetic pathway to these important natural furanoids. Herein, we disclose the subsequent discovery of a yield-boosting "missing link" carboxylesterase that selectively deprotects a late-stage intermediate, so triggering more efficient furan biosynthesis. This has allowed, for the first time, the isolation and structural elucidation of unknown intermediates, refining our understanding of furan formation in limonoid biosynthesis.

    View details for DOI 10.1021/jacs.4c11213

    View details for PubMedID 39418479

  • Reconstitution of early paclitaxel biosynthetic network. Nature communications Liu, J. C., De La Peña, R., Tocol, C., Sattely, E. S. 2024; 15 (1): 1419

    Abstract

    Paclitaxel is an anticancer therapeutic produced by the yew tree. Over the last two decades, a significant bottleneck in the reconstitution of early paclitaxel biosynthesis has been the propensity of heterologously expressed pathway cytochromes P450, including taxadiene 5α-hydroxylase (T5αH), to form multiple products. Here, we structurally characterize four new products of T5αH, many of which appear to be over-oxidation of the primary mono-oxidized products. By tuning the promoter strength for T5αH expression in Nicotiana plants, we observe decreased levels of these proposed byproducts with a concomitant increase in the accumulation of taxadien-5α-ol, the paclitaxel precursor, by three-fold. This enables the reconstitution of a six step biosynthetic pathway, which we further show may function as a metabolic network. Our result demonstrates that six previously characterized Taxus genes can coordinatively produce key paclitaxel intermediates and serves as a crucial platform for the discovery of the remaining biosynthetic genes.

    View details for DOI 10.1038/s41467-024-45574-8

    View details for PubMedID 38360800

    View details for PubMedCentralID PMC10869802

  • Complex scaffold remodeling in plant triterpene biosynthesis. Science (New York, N.Y.) De La Pena, R., Hodgson, H., Liu, J. C., Stephenson, M. J., Martin, A. C., Owen, C., Harkess, A., Leebens-Mack, J., Jimenez, L. E., Osbourn, A., Sattely, E. S. 2023; 379 (6630): 361-368

    Abstract

    Triterpenes with complex scaffold modifications are widespread in the plant kingdom. Limonoids are an exemplary family that are responsible for the bitter taste in citrus (e.g., limonin) and the active constituents of neem oil, a widely used bioinsecticide (e.g., azadirachtin). Despite the commercial value of limonoids, a complete biosynthetic route has not been described. We report the discovery of 22 enzymes, including a pair of neofunctionalized sterol isomerases, that catalyze 12 distinct reactions in the total biosynthesis of kihadalactone A and azadirone, products that bear the signature limonoid furan. These results enable access to valuable limonoids and provide a template for discovery and reconstitution of triterpene biosynthetic pathways in plants that require multiple skeletal rearrangements and oxidations.

    View details for DOI 10.1126/science.adf1017

    View details for PubMedID 36701471