Related Experiment Video
Updated: Nov 20, 2025
12:30
Synthesis of a Thiol Building Block for the Crystallization of a Semiconducting Gyroidal Metal-sulfur Framework
Published on: April 9, 2018
9.4K
Cryptic Sulfur Incorporation in Thioangucycline Biosynthesis
Mingming Cao1, Chengjian Zheng1, Dong Yang1
1Department of Chemistry, Department of Molecular Medicine, Natural Products Discovery Center at Scripps Research, The Scripps Research Institute, Jupiter, FL, 33458, USA.
Angewandte Chemie (International Ed. in English)
|January 19, 2021
Summary
This study reveals thioangucyclines (TACs) are formed non-enzymatically, possibly via hydrogen sulfide, suggesting a natural detoxification pathway. Gene deletion studies ruled out enzymatic involvement in this sulfur incorporation process.
Area of Science:
- Natural Product Biosynthesis
- Chemical Biology
- Microbial Metabolism
Background:
- Sulfur incorporation into natural products is a key area in biosynthesis.
- The mechanism of sulfur incorporation in angucycline biosynthesis remains poorly understood.
- Recent discovery of sulfur-containing angucyclines highlights knowledge gaps.
Purpose of the Study:
- To elucidate the biosynthetic pathway of thioether-bridged angucyclines (TACs).
- To identify the genes and mechanisms responsible for sulfur incorporation into angucyclines.
- To investigate the origin and potential function of TACs in microbial systems.
Main Methods:
- Discovery and characterization of novel thioether-bridged angucyclines.
- Identification of a cryptic epoxide intermediate in the proposed biosynthetic pathway.
- Systematic gene deletion of the relevant biosynthetic gene cluster (BGC) using CRISPR/Cas9.
- In vitro and in vivo experiments to assess the conversion of the epoxide intermediate.
- Analysis of potential involvement of endogenous hydrogen sulfide.
Main Results:
- A series of thioether-bridged angucyclines (TACs) were discovered.
- A cryptic epoxide Michael acceptor intermediate was identified en route to TACs A and B.
- CRISPR/Cas9-mediated gene deletion failed to identify any gene responsible for the epoxide to TAC conversion.
- In vitro and in vivo experiments demonstrated the conversion occurs via two non-enzymatic steps.
- Endogenous hydrogen sulfide was implicated as a potential mediator of the non-enzymatic conversion.
- TACs are proposed to originate from a detoxification process.
Conclusions:
- The biosynthesis of thioangucyclines (TACs) A and B does not involve specific enzymatic steps for sulfur incorporation.
- The formation of TACs is attributed to non-enzymatic reactions, likely mediated by hydrogen sulfide.
- This suggests that TACs may function as a detoxification mechanism for reactive intermediates.
- The findings contribute to understanding angucycline biosynthesis and the role of inorganic sulfur in natural product formation.
Related Concept Videos
01:20Sulfur Assimilation
182
Sulfur is an essential element in biological systems, contributing to synthesizing key biomolecules, including amino acids such as cysteine and methionine, and cofactors such as coenzyme A and biotin. Microorganisms primarily assimilate sulfur as sulfate (SO₄²⁻) from the environment, which must undergo a series of biochemical transformations before it can be incorporated into cellular components. As sulfate is highly oxidized, it must undergo assimilatory sulfate reduction to...
182
02:26Preparation and Reactions of Sulfides
5.4K
Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
5.4K
02:33Preparation and Reactions of Thiols
7.1K
Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
7.1K
02:17Structure and Nomenclature of Thiols and Sulfides
5.4K
Thiols and sulfides are sulfur analogs of alcohols and ethers, respectively, where the sulfur atom takes the place of the oxygen atom. Thus, thiols are generally represented as RSH, where R is an alkyl substituent and —SH is the functional group. On the other hand, in sulfides, the central sulfur atom is bonded to two hydrocarbon groups on either side. Depending upon the type of group, sulfides can be either symmetrical or asymmetrical. Both thiols and sulfides display a bent geometry,...
5.4K
01:22The Sulfur Cycle
51.1K
Sulfur, an important element in the chemical makeup of proteins, is recycled through the atmosphere and aquatic and terrestrial environments. Found in the atmosphere as sulfur dioxide (SO2), sulfur is released by decaying organisms, weathered rocks, geothermal vents, volcanos, and burning fossil fuels. It is deposited into the ecosystem, cycled through the biotic community, and either released back into the atmosphere as gas or deposited in marine sediment for long-term storage and eventual...
51.1K
01:22Electrophilic Aromatic Substitution: Sulfonation of Benzene
7.2K
Sulfonation of benzene is a reaction wherein benzene is treated with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is a mixture of sulfur trioxide and concentrated sulfuric acid.
7.2K