Ncl1-mediated metabolic rewiring critical during metabolic stress

Abstract

Nutritional limitation has been vastly studied; however, there is limited knowledge of how cells maintain homeostasis in excess nutrients. In this study, using yeast as a model system, we show that some amino acids are toxic at higher concentrations. With cysteine as a physiologically relevant example, we delineated the pathways/processes that are altered and those that are involved in survival in the presence of elevated levels of this amino acid. Using proteomics and metabolomics approach, we found that cysteine up-regulates proteins involved in amino acid metabolism, alters amino acid levels, and inhibits protein translation—events that are rescued by leucine supplementation. Through a comprehensive genetic screen, we show that leucine-mediated effect depends on a transfer RNA methyltransferase (NCL1), absence of which decouples transcription and translation in the cell, inhibits the conversion of leucine to ketoisocaproate, and leads to tricarboxylic acid cycle block. We therefore propose a role of NCL1 in regulating metabolic homeostasis through translational control.

Genome mining and UHPLC–QTOF–MS/MS to identify the potential antimicrobial compounds and determine the specificity of biosynthetic gene clusters in Bacillus subtilis NCD-2

“…During microbial synthesis of secondary metabolites, such as lipopeptide, the relatively high energyconsuming process of protein synthesis takes priority [56]. Excessive energy consumption is not conducive to the normal growth of microbes, and, generally, microbes produce antibiotics in large amounts only under stress, such as encountering pathogens [57].…”

Genome mining and UHPLC–QTOF–MS/MS illuminate the potential antimicrobial active compounds and specificity of biosynthetic gene clusters in Bacillus subtilis NCD-2

“…During the microbial synthesis of secondary metabolites, such as lipopeptide, the relatively high energy-consuming process of protein synthesis takes priority [61]. Excessive energy consumption is not conducive to the normal growth of microbes, and, generally, microbes produce antibiotics in large amounts only when encountering pathogens or other stresses [62].…”

Genome mining and UHPLC–QTOF–MS/MS to identify the potential antimicrobial compounds and determine the specificity of biosynthetic gene clusters in Bacillus subtilis NCD-2

“…During microbial synthesis of secondary metabolites, such as lipopeptide, the relatively high energy-consuming process of protein synthesis takes priority [56]. Excessive energy consumption is not conducive to the normal growth of microbes, and, generally, microbes produce antibiotics in large amounts only under stress, such as encountering pathogens [57].…”