Expanding tryptophan-containing cyclodipeptide synthase spectrum by identification of nine members from Streptomyces strains

Biotechnologically relevant enzymes and proteins
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Abstract

Cyclodipeptide synthases (CDPSs) comprise normally 200–300 amino acid residues and are mainly found in bacteria. They hijack aminoacyl-tRNAs from the ribosomal machinery for cyclodipeptide formation. In this study, nine new CDPS genes from eight Streptomyces strains were cloned into pET28a vector and expressed in Escherichia coli. Structural elucidation of the isolated products led to the identification of one cyclo-l-Trp-l-Leu, two cyclo-l-Trp-l-Pro, and three cyclo-l-Trp-l-Trp synthases. Other three CDPSs produce cyclo-l-Trp-l-Ala or cyclo-l-Trp-l-Tyr as the major cyclodipeptide. Total product yields of 46 to 211 mg/L E. coli culture were obtained. Our findings represent rare examples of CDPS family derived from actinobacteria that form various tryptophan-containing cyclodipeptides. Furthermore, this study highlights the potential of the microbial machinery for tryptophan-containing cyclodipeptide biosynthesis and provides valid experimental basis for further combination of these CDPS genes with other modification genes in synthetic biology.

Keywords

Aminoacyl t-RNA Diketopiperazine Cyclodipeptide synthase Streptomyces Tryptophan-containing cyclodipeptide 

Notes

Acknowledgements

We thank ARS Culture Collection (NRRL) for providing Streptomyces strains, S. Newel, and R. Kraut (University Marburg) for taking NMR and MS spectra.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and animal rights

This article does not contain any studies with human participants or animals performed by any of the authors.

Supplementary material

253_2018_8908_MOESM1_ESM.pdf (822 kb)
ESM 1 (PDF 821 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institut für Pharmazeutische Biologie und BiotechnologiePhilipps-Universität MarburgMarburgGermany

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