Biology subjects

Sattely, E.

Publications and source records attributed to Sattely, E..

3 recordsLinked to original sources

bioRxiv2018

A pathogen-responsive gene cluster for the production of highly modified fatty acids in tomato

In response to biotic stress, plants reshape their complement of lipids to produce suites of highly modified fatty acids that bear unusual chemical functionality. Despite their chemical complexity, proposed roles in pathogen defense and presence in crop plants, little is known about the biosynthesis of these decorated fatty acids. Falcarindiol is a prototypical member of a suite of acetylenic lipids from carrot, tomato, and celery that inhibits growth of several fungal strains and human cancer cell lines. Here we report a set of clustered genes in tomato (Solanum lycopersicum) that are required for the production of falcarindiol in leaves in response to treatment with an adapted fungal pathogen, Cladosporium fulvum. Our approach is based on correlation of untargeted transcriptomic and metabolomic data sets in order to rapidly identify a candidate biosynthetic pathway. By reconstituting the initial biosynthetic steps in a heterologous host (Nicotiana benthamiana) and generating stable transgenic pathway mutants in tomato, we demonstrate a direct role for three genes in the cluster in falcarindiol biosynthesis. This work reveals a mechanism by which plants sculpt their lipid pool in response to pathogens, and provides critical insight into the biochemistry of alkynyl lipid production.\n\nOne Sentence SummaryA biosynthetic gene cluster for the production of falcarindiol, a highly modified antifungal oxylipin found in edible plants.

plant biology↗

bioRxiv2018

N-hydroxy-pipecolic acid is a mobile signal that induces systemic disease resistance in Arabidopsis

Systemic acquired resistance (SAR) is a global response in plants induced at the site of infection that leads to long-lasting and broad-spectrum disease resistance at distal, uninfected tissues. Despite the importance of this priming mechanism, the identity of the mobile defense signal that moves systemically throughout plants to initiate SAR has remained elusive. In this paper, we describe a new metabolite, N-hydroxy-pipecolic acid (N-OH-Pip), and provide evidence that this molecule is a mobile signal that plays a central role in initiating SAR signal transduction in Arabidopsis thaliana. We demonstrate that FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1), a key regulator of SAR-associated defense priming, can synthesize N-OH-Pip from pipecolic acid in planta, and exogenously applied N-OH-PIP moves systemically in Arabidopsis and can rescue the SAR-deficiency of fmo1 mutants. We also demonstrate that N-OH-Pip treatment causes systemic changes in the expression of pathogenesis-related genes and metabolic pathways throughout the plant, and enhances resistance to a bacterial pathogen. This work provides new insight into the chemical nature of a mobile signal for SAR and also suggests that the N-OH-Pip pathway is a promising target for metabolic engineering to enhance disease resistance.

plant biology↗

bioRxiv2018

HEx: a heterologous expression platform for the discovery of fungal natural products

For decades, fungi have been a source of FDA-approved natural products such as penicillin, cyclosporine, and the statins. Recent breakthroughs in DNA sequencing suggest that millions of fungal species exist on Earth with each genome encoding pathways capable of generating as many as dozens of natural products. However, the majority of encoded molecules are difficult or impossible to access because the organisms are uncultivable or the genes are transcriptionally silent. To overcome this bottleneck in natural product discovery, we developed the HEx (Heterologous EXpression) synthetic biology platform for rapid, scalable expression of fungal biosynthetic genes and their encoded metabolites in Saccharomyces cerevisiae. We applied this platform to 41 fungal biosynthetic gene clusters from diverse fungal species from around the world, 22 of which produced detectable compounds. These included novel compounds with unexpected biosynthetic origins, particularly from poorly studied species. This result establishes the HEx platform for rapid discovery of natural products from any fungal species, even those that are uncultivable, and opens the door to discovery of the next generation of natural products.\n\nSummaryHere we present the largest scale effort reported to date toward the complete refactoring and heterologous expression of fungal biosynthetic gene clusters utilizing HEx, a novel synthetic biology platform.

synthetic biology↗