Norvaline and Norleucine May Have Been More Abundant Protein Components during Early Stages of Cell Evolution

Abstract

The absence of the hydrophobic norvaline and norleucine in the inventory of protein amino acids is readdressed. The well-documented intracellular accumulation of these two amino acids results from the low-substrate specificity of the branched-chain amino acid biosynthetic enzymes that act over a number of related α-ketoacids. The lack of absolute substrate specificity of leucyl-tRNA synthase leads to a mischarged norvalyl-tRNA(Leu) that evades the translational proofreading activities and produces norvaline-containing proteins, (cf. Apostol et al. J Biol Chem 272:28980-28988, 1997). A similar situation explains the presence of minute but detectable amounts of norleucine in place of methionine. Since with few exceptions both leucine and methionine are rarely found in the catalytic sites of most enzymes, their substitution by norvaline and norleucine, respectively, would have not been strongly hindered in small structurally simple catalytic polypeptides during the early stages of biological evolution. The report that down-shifts of free oxygen lead to high levels of intracellular accumulation of pyruvate and the subsequent biosynthesis of norvaline (Soini et al. Microb Cell Factories 7:30, 2008) demonstrates the biochemical and metabolic consequences of the development of a highly oxidizing environment. The results discussed here also suggest that a broader definition of biomarkers in the search for extraterrestrial life may be required.

Methionine in proteins: The Cinderella of the proteinogenic amino acids

“…Hence, the great flexibility of the methionyl side chain possibly depends more on the presence of a SC bond than on the lack of branching. That may help to explain, at least in part, why methionine was selected as a proteinogenic amino acid while norleucine, an unbranched structural analogous of methionine lacking sulfur, was not . Interestingly, norleucine can replace methionine and support normal bacterial protein synthesis under certain conditions.…”

“…That may help to explain, at least in part, why methionine was selected as a proteinogenic amino acid while norleucine, an unbranched structural analogous of methionine lacking sulfur, was not. 3 Interestingly, norleucine can replace methionine and support normal bacterial protein synthesis under certain conditions. However, norleucine-substituted cells exhibit a fitness lower than their wild type counterparts under conditions of oxidative stress.…”

Crystal structure of the tripeptideN-(benzyloxycarbonyl)glycylglycyl-L-norvaline

“…For information on the amino acid norvaline, see: ; Kisumi, Sugiura, Kato & Chibata (1976); Alvarez-Carreñ o et al (2013). For the conformation of glycine residues in proteins and peptides, see: Ramakrishnan & Srinivasan (1990).…”

Integrated Genomic and Proteomic Analyses of High-level Chloramphenicol Resistance in Campylobacter jejuni

“…Second, the import of methionine was increased by overexpression of the ABC transporter MetN. Methionine is the immediate precursor of SAM, which is one of the major methyl-group donors in trans-methylation reactions 29 . Third, two potential radical SAM enzymes were found to be associated with the SNP genes.…”