De novo cholesterol biosynthesis in bacteria
Alysha K Lee1, Jeremy H Wei1, Paula V Welander2
1Department of Earth System Science, Stanford University, Stanford, CA, 94305, USA.
Nature Communications
|May 22, 2023
Summary
Marine bacteria Enhygromyxa salina produce cholesterol, challenging previous understanding of bacterial sterol biosynthesis. This study reveals unique bacterial proteins involved in cholesterol modification, suggesting complex sterol pathways may be widespread in bacteria.
Area of Science:
- Biochemistry
- Microbiology
- Evolutionary Biology
Background:
- Eukaryotes synthesize complex sterols like cholesterol, vital for cell function.
- Bacterial sterol production is rare, with de novo cholesterol synthesis previously unreported.
Purpose of the Study:
- To investigate cholesterol production in the marine bacterium Enhygromyxa salina.
- To identify and characterize the bacterial cholesterol biosynthesis pathway.
- To compare bacterial and eukaryotic sterol biosynthesis mechanisms.
Main Methods:
- Bioinformatic analysis to identify the putative cholesterol biosynthesis pathway.
- Experimental validation of sterol production and modification.
- Comparative analysis of bacterial and eukaryotic sterol biosynthesis proteins.
Main Results:
- Enhygromyxa salina produces cholesterol and exhibits further downstream modifications.
- A putative cholesterol biosynthesis pathway homologous to the eukaryotic pathway was identified in E. salina.
- Unique bacterial proteins are responsible for complete C-4 demethylation, differentiating bacterial from eukaryotic pathways.
- Proteins from Calothrix sp. NIES-4105 also perform C-4 demethylation, indicating potential prevalence in other bacterial phyla.
Conclusions:
- Bacterial sterol production complexity can rival that of eukaryotes.
- Unique bacterial proteins mediate key steps in cholesterol biosynthesis.
- The findings suggest a complex evolutionary history of sterol biosynthesis across bacterial and eukaryotic domains.
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