Elizabeth Sattely

All Publications

• Two cytochromes P450 catalyze S-heterocyclizations in cabbage phytoalexin biosynthesis. Nature chemical biology Klein, A. P., Sattely, E. S. 2015; 11 (11): 837-839

  Abstract

  Phytoalexins are abundant in edible crucifers and have important biological activities, yet no dedicated gene for their biosynthesis is known. Here, we report two new cytochromes P450 from Brassica rapa (Chinese cabbage) that catalyze unprecedented S-heterocyclizations in cyclobrassinin and spirobrassinin biosynthesis. Our results provide genetic and biochemical insights into the biosynthesis of a prominent pair of dietary metabolites and have implications for pathway discovery across >20 recently sequenced crucifers.

  View details for DOI 10.1038/nchembio.1914

  View details for PubMedID 26389737

• A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence. Nature Rajniak, J., Barco, B., Clay, N. K., Sattely, E. S. 2015; 525 (7569): 376-379

  Abstract

  Thousands of putative biosynthetic genes in Arabidopsis thaliana have no known function, which suggests that there are numerous molecules contributing to plant fitness that have not yet been discovered. Prime among these uncharacterized genes are cytochromes P450 upregulated in response to pathogens. Here we start with a single pathogen-induced P450 (ref. 5), CYP82C2, and use a combination of untargeted metabolomics and coexpression analysis to uncover the complete biosynthetic pathway to 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), a previously unknown Arabidopsis metabolite. This metabolite harbours cyanogenic functionality that is unprecedented in plants and exceedingly rare in nature; furthermore, the aryl cyanohydrin intermediate in the 4-OH-ICN pathway reveals a latent capacity for cyanogenic glucoside biosynthesis in Arabidopsis. By expressing 4-OH-ICN biosynthetic enzymes in Saccharomyces cerevisiae and Nicotiana benthamiana, we reconstitute the complete pathway in vitro and in vivo and validate the functions of its enzymes. Arabidopsis 4-OH-ICN pathway mutants show increased susceptibility to the bacterial pathogen Pseudomonas syringae, consistent with a role in inducible pathogen defence. Arabidopsis has been the pre-eminent model system for studying the role of small molecules in plant innate immunity; our results uncover a new branch of indole metabolism distinct from the canonical camalexin pathway, and support a role for this pathway in the Arabidopsis defence response. These results establish a more complete framework for understanding how the model plant Arabidopsis uses small molecules in pathogen defence.

  View details for DOI 10.1038/nature14907

  View details for PubMedID 26352477

• Rapid Phytotransformation of Benzotriazole Generates Synthetic Tryptophan and Auxin Analogs in Arabidopsis. Environmental science & technology Lefevre, G. H., Müller, C. E., Li, R. J., Luthy, R. G., Sattely, E. S. 2015; 49 (18): 10959-10968

  Abstract

  Benzotriazoles (BTs) are xenobiotic contaminants widely distributed in aquatic environments and of emerging concern due to their polarity, recalcitrance, and common use. During some water reclamation activities, such as stormwater bioretention or crop irrigation with recycled water, BTs come in contact with vegetation, presenting a potential exposure route to consumers. We discovered that BT in hydroponic systems was rapidly (approximately 1-log per day) assimilated by Arabidopsis plants and metabolized to novel BT metabolites structurally resembling tryptophan and auxin plant hormones; <1% remained as parent compound. Using LC-QTOF-MS untargeted metabolomics, we identified two major types of BT transformation products: glycosylation and incorporation into the tryptophan biosynthetic pathway. BT amino acid metabolites are structurally analogous to tryptophan and the storage forms of auxin plant hormones. Critical intermediates were synthesized (authenticated by (1)H/(13)C NMR) for product verification. In a multiple-exposure temporal mass balance, three major metabolites accounted for >60% of BT. Glycosylated BT was excreted by the plants into the hydroponic medium, a phenomenon not observed previously. The observed amino acid metabolites are likely formed when tryptophan biosynthetic enzymes substitute synthetic BT for native indolic molecules, generating potential phytohormone mimics. These results suggest that BT metabolism by plants could mask the presence of BT contamination in the environment. Furthermore, BT-derived metabolites are structurally related to plant auxin hormones and should be evaluated for undesirable biological effects.

  View details for DOI 10.1021/acs.est.5b02749

  View details for PubMedID 26301449

• Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone. Science Lau, W., Sattely, E. S. 2015; 349 (6253): 1224-1228

  Abstract

  Podophyllotoxin is the natural product precursor of the chemotherapeutic etoposide, yet only part of its biosynthetic pathway is known. We used transcriptome mining in Podophyllum hexandrum (mayapple) to identify biosynthetic genes in the podophyllotoxin pathway. We selected 29 candidate genes to combinatorially express in Nicotiana benthamiana (tobacco) and identified six pathway enzymes, including an oxoglutarate-dependent dioxygenase that closes the core cyclohexane ring of the aryltetralin scaffold. By coexpressing 10 genes in tobacco-these 6 plus 4 previously discovered-we reconstitute the pathway to (-)-4'-desmethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Our results enable production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin.

  View details for DOI 10.1126/science.aac7202

  View details for PubMedID 26359402

• Key applications of plant metabolic engineering. PLoS biology Lau, W., Fischbach, M. A., Osbourn, A., Sattely, E. S. 2014; 12 (6)

  View details for DOI 10.1371/journal.pbio.1001879

  View details for PubMedID 24915445

• The chemical logic of plant natural product biosynthesis. Current opinion in plant biology Anarat-Cappillino, G., Sattely, E. S. 2014; 19: 51-58

  Abstract

  Understanding the logic of plant natural product biosynthesis is important for three reasons: it guides the search for new natural products and pathways, illuminates the function of existing pathways in the context of host biology, and builds an enabling 'parts list' for plant and microbial metabolic engineering. In this review, we highlight the chemical themes that underlie a broad range of plant pathways, dividing pathways into two parts: scaffold-generating steps that draw on a limited set of chemistries, and tailoring reactions that produce a wide range of end products from a small number of common scaffolds.

  View details for DOI 10.1016/j.pbi.2014.03.007

  View details for PubMedID 24727074

• Key applications of plant metabolic engineering. PLoS biology Lau, W., Fischbach, M. A., Osbourn, A., Sattely, E. S. 2014; 12 (6)

  Abstract

  Great strides have been made in plant metabolic engineering over the last two decades, with notable success stories including Golden rice. Here, we discuss the field's progress in addressing four long-standing challenges: creating plants that satisfy their own nitrogen requirement, so reducing or eliminating the need for nitrogen fertilizer; enhancing the nutrient content of crop plants; engineering biofuel feed stocks that harbor easy-to-access fermentable saccharides by incorporating self-destructing lignin; and increasing photosynthetic efficiency. We also look to the future at emerging areas of research in this field.

  View details for DOI 10.1371/journal.pbio.1001879

  View details for PubMedID 24915445

  View details for PubMedCentralID PMC4051588

• The chemical logic of plant natural product biosynthesis CURRENT OPINION IN PLANT BIOLOGY Anarat-Cappillino, G., Sattely, E. S. 2014; 19: 51-58

  View details for DOI 10.1016/j.pbi.2014.03.007

  View details for Web of Science ID 000338598300009

• Minimum set of cytochromes p450 for reconstituting the biosynthesis of camalexin, a major Arabidopsis antibiotic. Angewandte Chemie (International ed. in English) Klein, A. P., Anarat-Cappillino, G., Sattely, E. S. 2013; 52 (51): 13625-13628

  Abstract

  Bringing it all together: The missing key step in the biosynthesis of camalexin was uncovered by in vitro biochemical characterization. The coupling of Trp- and Cys-derived fragments through CS bond formation is promoted by an unusual cytochrome P450 CYP71A13. The in vitro reconstitution of the camalexin biosynthesis (left) from Trp and Cys was achieved using just three cytochromes P450. IAN=indole-3-acetonitrile.

  View details for DOI 10.1002/anie.201307454

  View details for PubMedID 24151049

• A Renewable Lignin-Lactide Copolymer and Application in Biobased Composites ACS SUSTAINABLE CHEMISTRY & ENGINEERING Chung, Y., Olsson, J. V., Li, R. J., Frank, C. W., Waymouth, R. M., Billington, S. L., Sattely, E. S. 2013; 1 (10): 1231-1238

  View details for DOI 10.1021/sc4000835

  View details for Web of Science ID 000325512000004

• Three Cytochromes P450 are Sufficient to Reconstitute the Biosynthesis of Camalexin, a Major Arabidopsis Antibiotic Angew. Chem. Int. Ed. Klein, A., P., Anarat-Cappillino, G., Sattely, E., S. 2013; 52: 13625-13628
• Design and Stereoselective Preparation of a New Class of Chiral Olefin Metathesis Catalysts and Application to Enantioselective Synthesis of Quebrachamine: Catalyst Development Inspired by Natural Product Synthesis J. Am. Chem. Soc. Sattely, E., S., Meek, S., J., Malcolmson, S., J., Schrock, R., R., Hoveyda, A., H. 2009; 131: 943- 953
• Three Siderophores from One Assembly Line Enzyme J. Am. Chem. Soc. Wuest, W., M., Sattely, E., S., Walsh, C., T. 2009; 131: 5056-5057
• Enzymatic Tailoring of Ornithine in the Biosynthesis of the Rhizobium Cyclic Trihydroxamate Siderophore Vicibactin J. Am. Chem. Soc. Heemstra Jr., J., R., Walsh, C., T., Sattely, E., S. 2009; 131: 15317-15329
• A Latent Oxazoline Electrophile for N-O-C Bond Formation in Pseudomonine Biosynthesis J. Am. Chem. Soc. Sattely, E., S., Walsh, C., T. 2008; 130: 12282-12284
• Total Biosynthesis: in vitro Reconstitution of Polyketide and Nonribosomal Peptide Pathways Nat. Prod. Rep. Sattely, E., S., Fischbach, M., A., Walsh, C., T. 2008; 25: 757-793
• Highly Efficient Molybdenum-Based Catalysts for Enantioselective Alkene Metathesis Nature Malcolmson, S., J., Meek, S., J., Sattely, E., S., Schrock, R., R., Hoveyda, A., H. 2008; 456: 933-937
• Enantioselective Synthesis of Cyclic Amines and Amides through Mo-Catalyzed Asymmetric Ring-Closing Metathesis J. Am. Chem. Soc. Sattely, E., S., Cortez, G., A., Moebius, D., C., Schrock, R., R., Hoveyda, A., H. 2005; 127: 8526-8533
• Efficient Catalytic Enantioselective Synthesis of Unsaturated Amines: Preparation of Small- and Medium- Ring Cyclic Amines through Mo-Catalyzed Asymmetric Ring-Closing Metathesis in the Absence of Solvent J. Am. Chem. Soc. Dolman, S., J., Sattely, E., S., Hoveyda, A., H., Schrock, R., R. 2002; 124: 6991-6997
• Catalytic Asymmetric Ring-Opening Metathesis/Cross Metathesis (AROM/CM) Reactions. Mechanism and Application to Enantioselective Synthesis of Functionalized Cyclopentanes J. Am. Chem. Soc. La, D., S., Sattely, E., S., Ford, J., G., Schrock, R., R., Hoveyda, A., H. 2001; 123: 7767-7778
• Tandem Catalytic Asymmetric Ring-Opening Metathesis/Cross Metathesis J. Am. Chem. Soc. La, D., S., Ford, J., G., Sattely, E., S., Bonitatebus, P., J., Schrock, R., R., Hoveyda, A., H. 1999; 121: 11603-11604