Cellular Stress-Induced Metabolites in Escherichia coli

Abstract

Escherichia coli isolates commonly inhabit the human microbiota, yet the majority of E. coli’s small-molecule repertoire remains uncharacterized. We previously employed erythromycin-induced translational stress to facilitate the characterization of autoinducer-3 (AI-3) and structurally related pyrazinones derived from “abortive” tRNA synthetase reactions in pathogenic, commensal, and probiotic E. coli isolates. In this study, we explored the “missing” tryptophan-derived pyrazinone reaction and characterized two other families of metabolites that were similarly upregulated under erythromycin stress. Strikingly, the abortive tryptophanyl-tRNA synthetase reaction leads to a tetracyclic indole alkaloid metabolite (1) rather than a pyrazinone. Furthermore, erythromycin induced two naphthoquinone-functionalized metabolites (MK-hCys, 2; and MK-Cys, 3) and four lumazines (7–10). Using genetic and metabolite analyses coupled with biomimetic synthesis, we provide support that the naphthoquinones are derived from 4-dihydroxy-2-naphthoic acid (DHNA), an intermediate in the menaquinone biosynthetic pathway, and the amino acids homocysteine and cysteine. In contrast, the lumazines are dependent on a flavin intermediate and α-ketoacids from the aminotransferases AspC and TyrB. We show that one of the lumazine members (9), an indole-functionalized analogue, possesses antioxidant properties, modulates the anti-inflammatory fate of isolated TH17 cells, and serves as an aryl-hydrocarbon receptor (AhR) agonist. These three systems described here serve to illustrate that new metabolic branches could be more commonly derived from well-established primary metabolic pathways.

Halogen Regulation in Vinylene-Linked Covalent Organic Frameworks for Efficient Photocatalytic C–H Thiolation of Quinone Derivatives

“…Besides, the stretching vibration peak of aldehyde (−CHO) for monomers at 1665 cm −1 disappeared, thereby suggesting that the highly polymerization degree was achieved for these COFs. 84,85 In addition, the peaks between 124.0 and 133.4 ppm in 13 C CP/MAS NMR of two carbon atoms of C�C further confirmed the formation of vinylene linkage (Figure S2). 86−88 Meanwhile, the peaks around 176.3, 176.6, and 177.8 ppm were attributed to the carbon atoms of the triazine ring, and the peaks around 152.3, 129.1, and 117.7 ppm were attributed to the adjacent carbon atoms with F, Cl, and Br atoms, respectively, thereby indicating that the triazine ring and the halogen atoms were successfully introduced into the skeleton.…”

“…Experimental procedures, materials and synthetic procedures, supporting figures, typical procedure for the products, and copies of 1 H and 13 C NMR spectra for the products (PDF)…”

“…The chemical structures were investigated by Fourier transform infrared (FT-IR) spectroscopy, 13 C cross-polarization/magic angle spinning solid-state nuclear magnetic resonance (CP/MAS ssNMR) spectroscopy, and thermogravimetric analysis (TGA). In the FT-IR spectrum, two new peaks around 1635 and 985 cm −1 are assigned to the stretching band of C�C bonds in F-COF, Cl-COF, and Br-COF (Figure S1), which indicates the successful formation of vinylene linkage.…”

“…Quinones are important chemicals in nature and are widely used in various therapeutic drugs, such as anticancer, antibacterial, antifungal, antiviral, and antimalarial, because of their various biological and pharmacological activities. − Naphthoquinone is a significant branch of quinones and is known for its various biological and pharmacological activities, which have been widely reported and studied. − In particular, the quinonyl aryl thioether is a kind of molecule with proven biological activity and has wonderful applications in the synthesis and design of valuable medicine. Currently, although various transition-metals-based catalysts were explored to mediate the thiolation of naphthoquinones, − some drawbacks, including high cost, high toxicity, and environmental pollution, have further restricted their development.…”

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

“…[ 1‐5 ] Although the detailed pathogenesis of psoriasis is still unclear, it is generally accepted that the pathogenesis of psoriasis is stimulated by keratinocyte hyperproliferation and excessive inflammatory response. [ 6‐10 ] Previous studies have shown that multiple cytokines, such as interleukin (IL)‐17 and tumor necrosis factor‐alpha (TNF‐ α ) are involved in the pathogenesis of psoriasis vulgaris. [ 11‐15 ] TNF‐ α, mainly derived from activated macrophages and monocytes, is an inflammatory cytokine produced during acute inflammation that can promote the proliferation and release of cytokines in epidermal keratinocytes.…”