RNA-Dependent Cysteine Biosynthesis in Bacteria and Archaea
Takahito Mukai1, Ana Crnković1, Takuya Umehara1,2
1Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
This study reveals a widespread alternative cysteine (Cys) biosynthesis system (SepRS-SepCysS) in diverse archaea and bacteria, suggesting ancient origins and horizontal gene transfer. This system impacts sulfur assimilation and various metabolic processes.
Area of Science:
- Microbial genetics
- Evolutionary biology
- Biochemistry
Background:
- The diversity of genetic code systems in microbes is not fully understood.
- Some methanogenic archaea use an alternative pathway for cysteine (Cys) biosynthesis and encoding, involving phosphoserine (Sep) and specific enzymes (SepRS, SepCysS).
Purpose of the Study:
- To investigate the distribution and evolution of the SepRS-SepCysS system in archaea and bacteria.
- To identify new clades of SepRS and SepCysS proteins across major archaeal and bacterial groups.
- To explore the relationship between this system and other genetic codes like selenocysteine (Sec) and pyrrolysine (Pyl).
Main Methods:
- Comprehensive search of genomic and metagenomic protein sequence data from public databases (IMG, NCBI).
- Bioinformatic analysis to identify SepRS, SepCysS, and SepCysE homologs.
- In vitro characterization of bacterial SepRS and SepCysS activity.
- Comparative analysis of gene distribution and co-occurrence with Sec and Pyl systems.
Main Results:
- New clades of SepRS and SepCysS proteins were identified in diverse archaea (DPANN, Euryarchaeota, TACK, Asgard) and bacteria (Parcubacteria, Chloroflexi).
- Bacterial SepRS and SepCysS were shown to charge tRNACys with cysteine in vitro.
- Homologs of the scaffold protein SepCysE were found in TACK and Asgard archaea, sometimes fused with SepCysS.
- Archaea with full-length SepCysE utilize Sec, while SepRS is common in Pyl-utilizing archaea and Chloroflexi.
- The SepRS-SepCysS system coexists with Pyl systems in both archaea and bacteria.
Conclusions:
- The SepRS-SepCysS system is more widespread than previously known, indicating significant evolutionary diversity in microbial genetic codes.
- Ancient archaea may have utilized both SepRS-SepCysS and Sec systems, with bacteria potentially acquiring the SepRS-SepCysS system from archaea.
- The SepRS-SepCysS system likely contributes to sulfur assimilation and metabolic processes requiring iron-sulfur or Pyl-containing enzymes, impacting global biogeochemical cycles.
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