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The tRNA-Dependent Biosynthesis of Modified Cyclic Dipeptides

Department of Chemistry/Biochemistry and LOEWE Center for Synthetic Microbiology (SYNMIKRO), Philipps-University Marburg, Hans-Meerwein-Strasse-4, 35032 Marburg, Germany
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Int. J. Mol. Sci. 2014, 15(8), 14610-14631; https://doi.org/10.3390/ijms150814610
Received: 18 June 2014 / Revised: 1 August 2014 / Accepted: 18 August 2014 / Published: 21 August 2014
(This article belongs to the Section Biochemistry)
In recent years it has become apparent that aminoacyl-tRNAs are not only crucial components involved in protein biosynthesis, but are also used as substrates and amino acid donors in a variety of other important cellular processes, ranging from bacterial cell wall biosynthesis and lipid modification to protein turnover and secondary metabolite assembly. In this review, we focus on tRNA-dependent biosynthetic pathways that generate modified cyclic dipeptides (CDPs). The essential peptide bond-forming catalysts responsible for the initial generation of a CDP-scaffold are referred to as cyclodipeptide synthases (CDPSs) and use loaded tRNAs as their substrates. After initially discussing the phylogenetic distribution and organization of CDPS gene clusters, we will focus on structural and catalytic properties of CDPSs before turning to two recently characterized CDPS-dependent pathways that assemble modified CDPs. Finally, possible applications of CDPSs in the rational design of structural diversity using combinatorial biosynthesis will be discussed before concluding with a short outlook. View Full-Text
Keywords: tRNA-dependent biosynthesis; cyclic dipeptides; cyclodipeptide synthases; CDPS (cyclodipeptide synthases); diketopiperazines; nocazines; combinatorial biosynthesis tRNA-dependent biosynthesis; cyclic dipeptides; cyclodipeptide synthases; CDPS (cyclodipeptide synthases); diketopiperazines; nocazines; combinatorial biosynthesis
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Giessen, T.W.; Marahiel, M.A. The tRNA-Dependent Biosynthesis of Modified Cyclic Dipeptides. Int. J. Mol. Sci. 2014, 15, 14610-14631.

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