Biology subjects

Artyukhin, A.

Publications and source records attributed to Artyukhin, A..

3 recordsLinked to original sources

bioRxiv2023

Evolutionarily related host and microbial pathways regulate fat desaturation

Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression1-4, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPAR in C. elegans. Untargeted metabolomics of a {beta}-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a {beta}- cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a {beta}-methyl fatty acid, bemeth#1, whose activity mimics that of microbiota-dependent becyp#1, but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated {beta}-oxidation pathway, while the endogenous bemeth#1 is metabolized via -oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPAR to regulate fat desaturation.

biochemistry↗

bioRxiv2021

A Keller-Segel model for C elegans L1 aggregation

We describe a mathematical model for the aggregation of starved first-stage C elegans larvae (L1s). We propose that starved L1s produce and respond chemotactically to two labile diffusible chemical signals, a short-range attractant and a longer range repellent. This model takes the mathematical form of three coupled partial differential equations, one that describes the movement of the worms and one for each of the chemical signals. Numerical solution of these equations produced a pattern of aggregates that resembled that of worm aggregates observed in experiments. We also describe the identification of a sensory receptor gene, srh-2, whose expression is induced under conditions that promote L1 aggregation. Worms whose srh-2 gene has been knocked out form irregularly shaped aggregates. Our model suggests this phenotype may be explained by the mutant worms slowing their movement more quickly than the wild type. Author summaryAmong the most complex of animal behaviors are collective behaviors, in which animals interact with each other so as to produce large-scale organization. Starved first-stage larvae of the nematode Caenorhabditis elegans exhibit such a behavior: they come together to form aggregates of several hundred worms. How and why they do this are unknown. To address these questions, we developed a mathematical model of starved L1 aggregation. This model reproduced the main features of the behavior.

animal behavior and cognition↗

bioRxiv2018

Metabolome-scale genome-wide association studies reveal chemical diversity and genetic control of maize specialized metabolites

One Sentence SummaryHPLC-MS metabolite profiling of maize seedlings, in combination with genome-wide association studies, identifies numerous quantitative trait loci that influence the accumulation of foliar metabolites.\n\nAbstractCultivated maize (Zea mays) retains much of the genetic and metabolic diversity of its wild ancestors. Non-targeted HPLC-MS metabolomics using a diverse panel of 264 maize inbred lines identified a bimodal distribution in the prevalence of foliar metabolites. Although 15% of the detected mass features were present in >90% of the inbred lines, the majority were found in <50% of the samples. Whereas leaf bases and tips were differentiated primarily by flavonoid abundance, maize varieties (stiff-stalk, non-stiff-stalk, tropical, sweet corn, and popcorn) were differentiated predominantly by benzoxazinoid metabolites. Genome-wide association studies (GWAS), performed for 3,991 mass features from the leaf tips and leaf bases, showed that 90% have multiple significantly associated loci scattered across the genome. Several quantitative trait locus hotspots in the maize genome regulate the abundance of multiple, often metabolically related mass features. The utility of maize metabolite GWAS was demonstrated by confirming known benzoxazinoid biosynthesis genes, as well as by mapping isomeric variation in the accumulation of phenylpropanoid hydroxycitric acid esters to a single linkage block in a citrate synthase-like gene. Similar to gene expression databases, this metabolomic GWAS dataset constitutes an important public resource for linking maize metabolites with biosynthetic and regulatory genes.

genetics↗