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The tRNA-dependent biosynthesis of modified cyclic dipeptides.
Tobias W Giessen1, Mohamed A Marahiel2
1Department of Chemistry/Biochemistry and LOEWE Center for Synthetic Microbiology (SYNMIKRO), Philipps-University Marburg, Hans-Meerwein-Strasse-4, 35032 Marburg, Germany. tobias.giessen@chemie.uni-marburg.de.
International Journal of Molecular Sciences
|September 9, 2014
Summary
Aminoacyl-tRNAs are vital beyond protein synthesis, serving roles in diverse cellular processes. This review highlights tRNA-dependent pathways for generating modified cyclic dipeptides (CDPs) using cyclodipeptide synthases (CDPSs).
Area of Science:
- Biochemistry
- Molecular Biology
- Synthetic Biology
Background:
- Aminoacyl-transfer RNAs (tRNAs) are essential for protein biosynthesis.
- Emerging roles for aminoacyl-tRNAs in diverse cellular processes including cell wall biosynthesis, lipid modification, protein turnover, and secondary metabolite assembly are recognized.
- Cyclic dipeptides (CDPs) are a class of modified compounds with significant biological relevance.
Purpose of the Study:
- To review tRNA-dependent biosynthetic pathways that generate modified cyclic dipeptides (CDPs).
- To explore the phylogenetic distribution, organization, structural, and catalytic properties of cyclodipeptide synthases (CDPSs).
- To discuss recently characterized CDPS-dependent pathways and potential applications in combinatorial biosynthesis.
Main Methods:
- Phylogenetic analysis of CDPS gene clusters.
- Structural and catalytic characterization of cyclodipeptide synthases.
- Review of literature on CDPS-dependent pathways and modified CDP assembly.
Main Results:
- Cyclodipeptide synthases (CDPSs) utilize loaded tRNAs as substrates to form CDP scaffolds.
- Two recently characterized CDPS-dependent pathways for assembling modified CDPs are presented.
- CDPSs offer potential for rational design of structural diversity through combinatorial biosynthesis.
Conclusions:
- CDPSs are key enzymes in tRNA-dependent CDP biosynthesis.
- Understanding CDPSs opens avenues for novel compound discovery and engineering.
- Further exploration of CDPSs can advance synthetic biology and drug development.
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