Metabolic Profiling Provides Unique Insights to Accumulation and Biosynthesis of Key Secondary Metabolites in Annual Pasture Legumes of Mediterranean Origin.

Annual legumes from the Mediterranean region are receiving attention in Australia as alternatives to traditional pasture species. The current study employed novel metabolic profiling approaches to quantify key secondary metabolites including phytoestrogens to better understand their biosynthetic regulation in a range of field-grown annual pasture legumes. In addition, total polyphenol and proanthocyanidins were quantified using Folin-Ciocalteu and vanillin assays, respectively. Metabolic profiling coupled with biochemical assay results demonstrated marked differences in the abundance of coumestans, flavonoids, polyphenols, and proanthocyanidins in annual pasture legume species. Genetically related pasture legumes segregated similarly from a chemotaxonomic perspective. A strong and positive association was observed between the concentration of phytoestrogens and upregulation of the flavonoid biosynthetic pathway in annual pasture legumes. Our findings suggest that evolutionary differences in metabolic dynamics and biosynthetic regulation of secondary metabolites have logically occurred over time in various species of annual pasture legumes resulting in enhanced plant defense.

PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease.

BACKGROUND: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation. RESULTS: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture. CONCLUSIONS: A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.

Chemometric analysis of Amaranthus retroflexus in relation to livestock toxicity in southern Australia.

Amaranthus retroflexus L., an introduced invasive weed in southern Australia, has been associated with acute renal failure and/or mortality in a number of livestock species. While its leaves, flowers and stems are generally reported to contain high levels of nitrogen, few studies have fully characterised the chemical composition of A. retroflexus foliage with respect to mammalian toxicity. We performed extensive metabolic profiling of stems, leaves, roots and inflorescence tissues of A. retroflexus collected from three spatially and/or temporally distinct toxicity outbreaks, and report on the 1) composition of primary and secondary metabolites in methanolic extracts of A. retroflexus tissues using HPLC and HPLC-MS QToF and 2) chemometric analysis of A. retroflexus extracts in relation to the associated toxin(s). All tissues of A. retroflexus possessed an abundance of N-containing metabolites, particularly quaternary ammonium compounds which were identified as betaines, two of which (valine betaine and isoleucine betaine) are rarely encountered in plants. Cytotoxicity to murine fibroblasts was highest in extracts of leaf tissue and was associated with a single, a small modified peptide with high similarity to N-acetyl-L-α-aspartyl-L-alanyl-L-α-aspartyl-L-α-glutamyl-O-(carboxymethyl)-L-tyrosyl-L-leucinamide, a synthetic phosphotyrosyl mimic involved in cell signaling processes. One possible mode of action leading to acute renal failure in grazing livestock by a modified peptide such as this is proposed.