A Comprehensive Overview of the Cyclodipeptide Synthase Family Enriched with the Characterization of 32 New Enzymes

Frontiers in Microbiology
Muriel GondryMireille Moutiez

Abstract

Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100. We detect 16 new cyclodipeptides, one of which containing an arginine which has never been observed previously. This brings to 75 the number of cyclodipeptides formed by CDPSs out of the possible 210 natural ones. We also identify several consensus sequences related to the synthesis of a specific cyclodipeptide, improving the predictive model of CDPS specificity. The improved prediction method enables to propose the main product synthesized for about 80% of the CDPS sequences available in databases and opens the way for the deciphering of CDPS-dependent pathways. Analysis of phylum distribution and predicted activity for all CDPSs identified in databases shows that t...Continue Reading

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Citations

Sep 16, 2018·RNA·Howard Gamper, Ya-Ming Hou
Jul 19, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Marat A ZiganshinValery V Gorbatchuk
Aug 19, 2020·Chemical Communications : Chem Comm·Jing LiuShu-Ming Li
Jun 22, 2019·Annual Review of Microbiology·Stephen Dela Ahator, LianHui Zhang
Dec 29, 2019·Scientific Reports·Jerzy WitwinowskiEmmanuelle Darbon
Feb 25, 2021·Applied Microbiology and Biotechnology·Lauritz Harken, Shu-Ming Li
May 4, 2021·RSC Chemical Biology·Christopher J HardingClarissa M Czekster
Dec 24, 2019·Chemical Reviews·Jason B Hedges, Katherine S Ryan

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Software Mentioned

Seaview
AlbC
Muscle
GeneArt
PhyML
BLAST
HHPred
iTOL

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