Ethylene activation of carotenoid biosynthesis by a novel transcription factor CsERF061

Chromoplast-specific lycopene β-cyclase (LCYb2) is a critical carotenogenic enzyme, which controls the massive accumulation of downstream carotenoids, especially provitamin A carotenoids, in citrus. Its regulatory metabolism is largely unknown. Here, we identified a group I ethylene response factor, CsERF061, in citrus by yeast one-hybrid screen with the promoter of LCYb2. The expression of CsERF061 was induced by ethylene. Transcript and protein levels of CsERF061 were increased during fruit development and coloration. CsERF061 is a nucleus-localized transcriptional activator, which directly binds to the promoter of LCYb2 and activates its expression. Overexpression of CsERF061 in citrus calli and tomato fruits enhanced carotenoid accumulation by increasing the expression of key carotenoid pathway genes, and increased the number of chromoplasts needed to sequester the elevated concentrations of carotenoids, which was accompanied by changes in the concentrations of abscisic acid and gibberellin. Electrophoretic mobility shift and dual-luciferase assays verified that CsERF061 activates the promoters of nine other key carotenoid pathway genes, PSY1, PDS, CRTISO, LCYb1, BCH, ZEP, NCED3, CCD1, and CCD4, revealing the multitargeted regulation of CsERF061. Collectively, our findings decipher a novel regulatory network of carotenoid enhancement by CsERF061, induced by ethylene, which will be useful for manipulating carotenoid accumulation in citrus and other plants.

Profiling of Endogenous and Gut Microbial Metabolites to Indicate Metabotype-Specific Dietary Responses: A Systematic Review

ABSTRACT Upon dietary exposure, the endogenous metabolism responds to the diet-derived nutrients and bioactive compounds, such as phytochemicals. However, the responses vary remarkably due to the interplay with other dietary components, lifestyle exposures, and intrinsic factors, which lead to differences in endogenous regulatory metabolism. These physiological processes are evidenced as a signature profile composed of various metabolites constituting metabolic phenotypes, or metabotypes. The metabolic profiling of biological samples following dietary intake hence would provide information about diet—that is, as the intake biomarkers and the ongoing physiological reactions triggered by this intake—thereby enable evaluation of the metabolic basis required to distinguish the different metabotypes. The capacity of nontargeted metabolomics to also encompass the unprecedented metabolite species has enabled the profiling of multiple metabolites and the corresponding metabotypes with a single analysis, decoding the complex interplay between diet, other relevant factors, and health. In this systematic review, we screened 345 articles published in English in January 2007–July 2018, which applied the metabolomics approach to profile the changes of endogenous metabolites in the blood related to dietary interventions, either derived by metabolism of gut microbiota or the human host. We excluded all the compounds that were directly derived from diet, and also the dietary interventions focusing on supplementation with individual compounds. After the removal of less relevant studies and assessment of eligibility, 49 articles were included in this review. First, we mention the contribution of individual factors, either modifiable or nonmodifiable factors, in shaping metabolic profile. Then, how different aspects of the diet would affect the metabolic profiles are disentangled. Next, the classes of endogenous metabolites altered following included dietary interventions are listed. We also discuss the current challenges in the field, along with future research opportunities.

Modulation of Disordered Proteins with a Focus on Neurodegenerative Diseases and Other Pathologies

Intrinsically disordered proteins (IDPs) do not have rigid 3D structures, showing changes in their folding depending on the environment or ligands. Intrinsically disordered proteins are widely spread in eukaryotic genomes, and these proteins participate in many cell regulatory metabolism processes. Some IDPs, when aberrantly folded, can be the cause of some diseases such as Alzheimer′s, Parkinson′s, and prionic, among others. In these diseases, there are modifications in parts of the protein or in its entirety. A common conformational variation of these IDPs is misfolding and aggregation, forming, for instance, neurotoxic amyloid plaques. In this review, we discuss some IDPs that are involved in neurodegenerative diseases (such as beta amyloid, alpha synuclein, tau, and the “IDP-like” PrP), cancer (p53, c-Myc), and diabetes (amylin), focusing on the structural changes of these IDPs that are linked to such pathologies. We also present the IDP modulation mechanisms that can be explored in new strategies for drug design. Lastly, we show some candidate drugs that can be used in the future for the treatment of diseases caused by misfolded IDPs, considering that cancer therapy has more advanced research in comparison to other diseases, while also discussing recent and future developments in this area of research. Therefore, we aim to provide support to the study of IDPs and their modulation mechanisms as promising approaches to combat such severe diseases.