About

Elizabeth Sattely is an Associate Professor of Chemical Engineering at Stanford University. Her research focuses on the extraordinary capacity of plants to harvest atmospheric CO2 and sunlight for the production of energy-rich biopolymers, clinically used drugs, and other biologically active small molecules. Her work involves elucidating and engineering plant metabolism to develop sustainable biofuel feedstocks, protect crops from pathogens, and discover new natural-product based therapeutics for human disease. She employs a multidisciplinary approach combining chemistry, enzymology, genetics, and metabolomics to address problems such as new methods for delignification of lignocellulosic biomass and the engineering of plant antibiotic biosynthesis.

Research topics

• Biology
• Genetics
• Biochemistry
• Botany
• Chemistry
• Computer Science
• Cell biology
• Microbiology
• Immunology
• Stereochemistry
• Computational biology

Selected publications

• Identification and characterization of dietary antigens in oral tolerance

  Science Immunology · 2026-03-06 · 1 citations

  articleSenior authorCorresponding

  Food antigens elicit immune tolerance through the action of intestinal regulatory T (T reg ) cells. Unlike food allergens, the proteins that mediate tolerance are mostly undescribed. Here, we found that epitopes derived from seed storage proteins are targets of murine intestinal T reg cells, with the most frequent response targeting the C terminus of the maize protein alpha-zein. A major histocompatibility complex (MHC) tetramer loaded with this antigen revealed that zein-specific T cells are predominantly intestinal T reg cells, develop concurrently with weaning, and constitute up to 2% of the peripheral T reg cell pool. Zein-responsive T reg cells repressed naïve T cell proliferation ex vivo, and prior dietary exposure resulted in a constrained response upon diverse inflammatory challenges in vivo, supporting a specific role for gut-resident T reg cells in suppressing systemic immune responses. Our work reveals the development, immune-suppressive characteristics, and function of naturally occurring T reg cells that recognize dietary seed storage proteins, a previously undescribed class of antigens in oral tolerance.

  PublisherDOI

• A single-cell screening platform accelerates functional genetics in plants

  Nature Biotechnology · 2026-05-05

  articleSenior author
  PublisherDOI

• Discovery of cephalotaxinone enzymes reveals a whole plant model for homoharringtonine biosynthesis

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-29

  preprintOpen accessSenior authorCorresponding

  ABSTRACT Plants produce diverse molecules that inhibit protein translation. A lead example is homoharringtonine (HHT), a key tool for ribosomal profiling and an FDA-approved treatment for chronic myeloid leukemia. HHT is commercially produced through semi-synthesis from the alkaloid core cephalotaxine (CET) extracted from endangered Cephalotaxus species. Despite its significance, the CET/HHT biosynthetic pathway remains unresolved. Here, we use paired untargeted metabolomics (stable-isotope precursor feeding) and transcriptomics to elucidate a near-complete biosynthesis to CET without prior knowledge of intermediates and biosynthetic genes. We show that while the CET core is biosynthesized only in growing root tips, CET and HHT accumulate throughout the plant. We discovered seven pathway intermediates and six novel enzymes that produce cephalotaxinone, the likely direct precursor of CET. Included are non-canonical cytochrome P450s, an atypical short-chain dehydrogenase, and a 2-oxoglutarate-dependent dioxygenase that together result in carbon excision and CET/HHT pentacyclic backbone formation. This study establishes a metabolic route to the HHT core scaffold and suggests a whole-plant coordination model in Cephalotaxus , where cephalotaxinone is produced in root tips and distributed throughout the plant for subsequent elaboration to HHT.

  PublisherOA PDFDOI

• Discovery of FoTO1 and Taxol genes enables biosynthesis of baccatin III

  Nature · 2025-06-11 · 57 citations

  articleOpen accessSenior author

  Abstract Plants make complex and potent therapeutic molecules 1,2 , but sourcing these molecules from natural producers or through chemical synthesis is difficult, which limits their use in the clinic. A prominent example is the anti-cancer therapeutic paclitaxel (sold under the brand name Taxol), which is derived from yew trees ( Taxus species) 3 . Identifying the full paclitaxel biosynthetic pathway would enable heterologous production of the drug, but this has yet to be achieved despite half a century of research 4 . Within Taxus ’ large, enzyme-rich genome 5 , we suspected that the paclitaxel pathway would be difficult to resolve using conventional RNA-sequencing and co-expression analyses. Here, to improve the resolution of transcriptional analysis for pathway identification, we developed a strategy we term multiplexed perturbation × single nuclei (mpXsn) to transcriptionally profile cell states spanning tissues, cell types, developmental stages and elicitation conditions. Our data show that paclitaxel biosynthetic genes segregate into distinct expression modules that suggest consecutive subpathways. These modules resolved seven new genes, allowing a de novo 17-gene biosynthesis and isolation of baccatin III, the industrial precursor to Taxol, in Nicotiana benthamiana leaves, at levels comparable with the natural abundance in Taxus needles. Notably, we found that a nuclear transport factor 2 (NTF2)-like protein, FoTO1, is crucial for promoting the formation of the desired product during the first oxidation, resolving a long-standing bottleneck in paclitaxel pathway reconstitution. Together with a new β-phenylalanine-CoA ligase, the eight genes discovered here enable the de novo biosynthesis of 3’- N -debenzoyl-2’-deoxypaclitaxel. More broadly, we establish a generalizable approach to efficiently scale the power of co-expression analysis to match the complexity of large, uncharacterized genomes, facilitating the discovery of high-value gene sets.

  PublisherOA PDFDOI

• An <i>in planta</i> single-cell screen to accelerate functional genetics

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-07 · 3 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Genetic screens in whole plants are a powerful tool for functional genetics. However, elucidating gene function in highly redundant genetic programs such as signaling pathways remains challenging in both model and non-model plants. Here, we report a single-cell screening platform, PIVOT (Protoplast Isolation after Virus Overexpression in planTa ), to accelerate identification and functional characterization of plant genes. We used Nicotiana benthamiana as a heterologous host to test gene libraries arrayed in a single leaf. Two elements of our system made pooled screens possible in planta : (1) we harnessed viral superinfection exclusion to ensure single multiplicity of infection per cell during pooled library delivery, and (2) we engineered a cell surface protein as a phenotypic marker for isolating cells of interest from a heterogeneous population. Using this system, we recovered known and new regulators of cytokinin signaling from an Arabidopsis open reading frame library. We anticipate PIVOT will be broadly applicable for high-throughput, single-cell functional genetic screening across the plant kingdom.

  PublisherOA PDFDOI

• Transcriptome analysis reveals role of transcription factor WRKY70 in early <i>N-</i>hydroxy-pipecolic acid signaling

  PLANT PHYSIOLOGY · 2024-10-15 · 8 citations

  articleOpen access

  N-Hydroxy-pipecolic acid (NHP) is a mobile metabolite essential for inducing and amplifying systemic acquired resistance (SAR) following a pathogen attack. Early phases of NHP signaling leading to immunity have remained elusive. Here, we report the early transcriptional changes mediated by NHP and the role salicylic acid (SA) plays during this response in Arabidopsis (Arabidopsis thaliana). We show that distinct waves of expression within minutes to hours of NHP treatment include increased expression of WRKY transcription factor genes as the primary transcriptional response, followed by the induction of WRKY-regulated defense genes as the secondary response. Most genes induced by NHP within minutes were SA dependent, whereas those induced within hours were SA independent. These data suggest that NHP induces the primary transcriptional response under basal levels of SA and that new SA biosynthesis via ISOCHORISMATE SYNTHASE 1/SA-INDUCTION DEFICIENT 2 is dispensable for inducing the secondary transcriptional response. We demonstrate that WRKY70 is required for the induced expression of a set of genes defining some of the secondary transcriptional response, SAR protection, and NHP-dependent enhancement of reactive oxygen species production in response to flagellin treatment. Our study highlights the key genes and pathways defining early NHP responses and the role of WRKY70 in regulating NHP-dependent transcription.

  PublisherOA PDFDOI

• Reconstitution of early paclitaxel biosynthetic network

  Nature Communications · 2024-02-15 · 66 citations

  articleOpen accessSenior author

  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.

  PublisherOA PDFDOI

• Identification and characterization of dietary antigens in oral tolerance

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-05-29 · 9 citations

  preprintOpen accessSenior authorCorresponding

  Food antigens elicit immune tolerance through the action of regulatory T cells (Tregs) in the intestine. Although antigens that trigger common food allergies are known, the epitopes that mediate tolerance to most foods have not been described. Here, we identified murine T cell receptors specific for maize, wheat, and soy, and used expression cloning to de-orphan their cognate epitopes. All of the epitopes derive from seed storage proteins that are resistant to degradation and abundant in the edible portion of the plant. Multiple unrelated T cell clones were specific for an epitope at the C-terminus of 19 kDa alpha-zein, a protein from maize kernel. An MHC tetramer loaded with this antigen revealed that zein-specific T cells are predominantly Tregs localized to the intestine. These cells, which develop concurrently with weaning, constitute up to 2% of the peripheral Treg pool. Bulk and single-cell RNA sequencing revealed that these cells express higher levels of immunosuppressive markers and chemokines compared to other Tregs. These data suggest that immune tolerance to plant-derived foods is focused on a specific class of antigens with common features, and they reveal the functional properties of naturally occurring food-specific Tregs.

  PublisherOA PDFDOI

• Multiplexed perturbation of yew reveals cryptic proteins that enable a total biosynthesis of baccatin III and Taxol precursors

  bioRxiv (Cold Spring Harbor Laboratory) · 2024-11-08 · 10 citations

  preprintOpen accessSenior authorCorresponding

  Abstract Plants make complex and potent therapeutic molecules, but difficulties in sourcing from natural producers or chemical synthesis can challenge their use in the clinic. A prominent example is the anti-cancer therapeutic paclitaxel (Taxol ® ). Identification of the full paclitaxel biosynthetic pathway would enable heterologous drug production, but it has eluded discovery despite a half century of intensive research. Within the search space of Taxus’ large, enzyme-rich genome, we suspected the complex paclitaxel pathway would be difficult to resolve using conventional gene co-expression analysis and small sample sets. To improve the resolution of gene set identification, we developed a multiplexed perturbation strategy to transcriptionally profile cell states spanning tissues, cell types, developmental stages, and elicitation conditions. This approach revealed a set of paclitaxel biosynthetic genes that segregate into expression modules that suggest consecutive biosynthetic sub-pathways. These modules resolved seven new genes that, when combined with previously known enzymes, are sufficient for the de novo biosynthesis and isolation of baccatin III, an industrial precursor for Taxol, in Nicotiana benthamiana leaves at levels comparable to the natural abundance in Taxus needles. Included are taxane 1β-hydroxylase (T1βH), taxane 9α-hydroxylase (T9αH), taxane 7β- O -acyltransferase (T7ΑΤ), taxane 7β- O -deacetylase (T7dA), taxane 9α- O -deacetylase (T9dA), and taxane 9-oxidase (T9ox). Importantly, the T9αH we discovered is distinct and independently evolved from those recently reported, which failed to yield baccatin III with downstream enzymes. Unexpectedly, we also found a nuclear transport factor 2 (NTF2)-like protein (FoTO1) crucial for high yields of taxanes; this gene promotes the formation of the desired product during the first taxane oxidation step, resolving a longstanding bottleneck in paclitaxel pathway reconstitution. Together with a new β-phenylalanine-CoA-ligase, the eight genes discovered in this study enables the complete reconstitution of 3’- N -debenzoyl-2’-deoxy-paclitaxel with a 20-enzyme pathway in Nicotiana plants. More broadly, we establish a generalizable approach for pathway discovery that scales the power of co-expression studies to match the complexity of specialized metabolism, enabling discovery of gene sets responsible for high-value biological functions.

  PublisherOA PDFDOI

• Specific derivatization of internal alkynes for improved electrospray analysis

  ChemRxiv · 2024-05-29

  preprintOpen accessSenior author

  Many plant and fungal species, including foods, produce specialized metabolites that contain internal alkynes. Specific detection and analysis of naturally produced internal alkynes is often difficult, because of poor ionization, thermal instability, and a lack of internal-alkyne-specific chemical tools to facilitate analysis. We developed a derivatization protocol for improved LC-MS analysis of internal alkynes. The method exploits the ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) reaction to form trisubstituted triazoles, species with vastly improved electrospray ionization efficiencies compared to many naturally occurring internal alkynes. The method can be used in crude biological extracts and other complex samples, and increases the ionization efficiency by up to 32,000-fold. Additionally, using a fast (1 minute), direct LC-MS analysis of RuAAC reactions during derivatization, we observed the kinetics of formation and depletion of variety of catalyst-derived ruthenium complexes, some of which may provide mechanistic insight into the limitations of the RuAAC derivatization. We use this derivatization in the course of isolating a dietary internal alkyne from a hedgehog mushroom. This molecule proved to be a previously unreported analog of repandiol.

  PublisherOA PDFDOI

Recent grants

• NIH Grant DP2AT00832101

  NIH · $2.4M · 2018

• NIH Grant K99GM089985

  NIH · $90k · 2010

• NIH Grant R00GM089985

  NIH · $738k · 2015

• Discovery and Engineering of Plant Natural Product Pathways

  NIH · $2.3M · 2017–2025

Frequent coauthors

• Amir H. Hoveyda

  Université de Strasbourg

  30 shared

• Richard R. Schrock

  University of California, Riverside

  30 shared

• Anne Osbourn

  John Innes Centre

  18 shared

• Mary Beth Mudgett

  Stanford University

  16 shared

• Michael J. Stephenson

  University of East Anglia

  16 shared

• Hannah Hodgson

  John Innes Centre

  16 shared

• Curt R. Fischer

  Stanford University

  14 shared

• Ricardo De La Peña

  Stanford University

  12 shared

Education

• Ph.D., Chemical Engineering

  Stanford University

  2009

• B.S., Chemical Engineering

  University of California, Berkeley

  2004