Dataset Information

Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum.

ABSTRACT: The anaerobe Clostridium acetobutylicum belongs to the most important industrially used bacteria. Whereas genome mining points to a high potential for secondary metabolism in C. acetobutylicum, the functions of most biosynthetic gene clusters are cryptic. We report that the addition of supra-physiological concentrations of cysteine triggered the formation of a novel natural product, clostrisulfone (1). Its structure was fully elucidated by NMR, MS and the chemical synthesis of a reference compound. Clostrisulfone is the first reported natural product with a diphenylsulfone scaffold. A biomimetic synthesis suggests that pentamethylchromanol-derived radicals capture sulfur dioxide to form 1. In a cell-based assay using murine macrophages a biphasic and dose-dependent regulation of the LPS-induced release of nitric oxide was observed in the presence of 1.

SUBMITTER: Neuwirth T

PROVIDER: S-EPMC7756337 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum.

Neuwirth Toni T Letzel Anne-Catrin AC Tank Cedric C Ishida Keishi K Cyrulies Michael M Schmölz Lisa L Lorkowski Stefan S Hertweck Christian C

Chemistry (Weinheim an der Bergstrasse, Germany) 20201103 68

The anaerobe Clostridium acetobutylicum belongs to the most important industrially used bacteria. Whereas genome mining points to a high potential for secondary metabolism in C. acetobutylicum, the functions of most biosynthetic gene clusters are cryptic. We report that the addition of supra-physiological concentrations of cysteine triggered the formation of a novel natural product, clostrisulfone (1). Its structure was fully elucidated by NMR, MS and the chemical synthesis of a reference compou ...[more]

PMID: 32996646

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Project description:The acetone-butanol (AB) fermentation process in the anaerobic endospore-forming Gram-positive bacterium Clostridium acetobutylicum is useful as a producer of biofuels, particularly butanol. Recent work has concentrated on trying to improve the efficiency of the fermentation method, either through changes in the environmental conditions or by modifying the genome to selectively favour the production of one particular solvent over others. Fermentation of glucose by C. acetobutylicum occurs in two stages: initially the acids acetate and butyrate are produced and excreted and then, as the external pH falls, acetate and butyrate are ingested and further metabolised into the solvents acetone, butanol and ethanol. In order to optimise butanol production, it is important to understand how pH affects the enzyme-controlled reactions in the metabolism process. We adapt an ordinary differential equation model of the metabolic network with regulation at the genetic level for the required enzymes; parametrising the model using experimental data generated from continuous culture, we improve on previous point predictions (S. Haus, S. Jabbari, T. Millat, H. Janssen, R.-J. Fisher, H. Bahl, J. R. King, O. Wolkenhauer, A systems biology approach to investigate the effect of pH-induced gene regulation on solvent production by Clostridium acetobutylicum in continuous culture, BMC Systems Biology 5 (2011)) [1] both by using a different optimisation approach and by computing confidence intervals and correlation coefficients. We find in particular that the parameters are ill-determined from the data and that two separate clusters of parameters appear correlated, reflecting the importance of two metabolic intermediates. We extend the model further to include another aspect of the clostridial survival mechanism, sporulation, and by computation of the Akaike Information Criterion values find that the there is some evidence for the presence of sporulation during the shift.

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Dataset Information

Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum.

Publications

Induced Production, Synthesis, and Immunomodulatory Action of Clostrisulfone, a Diarylsulfone from Clostridium acetobutylicum.

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