Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jun 28;9(7):1396.
doi: 10.3390/microorganisms9071396.

Discovery and Heterologous Production of New Cyclic Depsibosamycins

Marc Stierhof  1 , Maksym Myronovskyi  1 , Josef Zapp  2 , Andriy Luzhetskyy  1   3
Affiliations

Discovery and Heterologous Production of New Cyclic Depsibosamycins

Marc Stierhof et al. Microorganisms. .

Abstract

Streptomyces are producers of valuable secondary metabolites with unique scaffolds that perform a plethora of biological functions. Nonribosomal peptides are of special interest due to their variety and complexity. They are synthesized by nonribosomal peptide synthetases, large biosynthetic machineries that are encoded in the genome of many Streptomyces species. The identification of new peptides and the corresponding biosynthetic gene clusters is of major interest since knowledge can be used to facilitate combinatorial biosynthesis and chemical semisynthesis of natural products. The recently discovered bosamycins are linear octapeptides with an interesting 5-OMe tyrosine moiety and various modifications at the N-terminus. In this study, the new cyclic depsibosamycins B, C, and D from Streptomyces aurantiacus LU19075 were discovered. In comparison to the linear bosamycins B, C, and D, which were also produced by the strain, the cyclic depsibosamycins showed a side-chain-to-tail lactonization of serine and glycine, leading to a ring of four amino acids. In silico identification and heterologous expression of the depsibosamycin (dbm) gene cluster indicated that the cyclic peptides, rather than the linear derivatives, are the main products of the cluster.

Keywords: NRPS; Streptomyces; bosamycin; cyclic peptide; heterologous expression.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure comparison of compounds with a similar side-chain-to-tail lactone ring (red) formed by an intramolecular reaction of β-hydroxy amino acids and the C-terminus.
Figure 2
Figure 2
LC-MS chromatogram of the butanol extract of Streptomyces aurantiacus LU19075 cultivated in DNPM medium showing the peaks of bosamycins B, C, and D (*) and depsibosamycins B, C, and D (**). In addition to that, nactins (17–20 min) and nactin degradation products (9–16 min) were identified.
Figure 3
Figure 3
Structures of bosamycins B, C, and D and depsibosamycins B, C, and D.
Figure 4
Figure 4
Alignment of the bosamycin (bsm) cluster (a) and the depsibosamycin (dbm) cluster (b) revealed 99.2% similarity.
Figure 5
Figure 5
Depsibosamycin C and bosamycin C production in S. aurantiacus LU19075 over the course of 6 days.
See this image and copyright information in PMC

References

    1. Barka E.A., Vatsa P., Sanchez L., Gaveau-Vaillant N., Jacquard C., Klenk H.-P., Clément C., Ouhdouch Y., van Wezel G.P. Taxonomy, Physiology, and Natural Products of Actinobacteria. Microbiol. Mol. Biol. Rev. 2016;80:1–43. doi: 10.1128/MMBR.00019-15. - DOI - PMC - PubMed
    1. Chen Y., Ntai I., Ju K.-S., Unger M., Zamdborg L., Robinson S.J., Doroghazi J.R., Labeda D.P., Metcalf W.W., Kelleher N.L. A Proteomic Survey of Nonribosomal Peptide and Polyketide Biosynthesis in Actinobacteria. J. Proteome Res. 2011;11:85–94. doi: 10.1021/pr2009115. - DOI - PMC - PubMed
    1. Běhal V. Bioactive products from streptomyces. Adv. Virus Res. 2000;47:113–156. doi: 10.1016/s0065-2164(00)47003-6. - DOI - PubMed
    1. Strieker M., Tanović A., Marahiel M.A. Nonribosomal peptide synthetases: Structures and dynamics. Curr. Opin. Struct. Biol. 2010;20:234–240. doi: 10.1016/j.sbi.2010.01.009. - DOI - PubMed
    1. Bozhüyük K.A.J., Linck A., Tietze A., Kranz J., Wesche F., Nowak S., Fleischhacker F., Shi Y.-N., Grün P., Bode H.B. Modification and de novo design of non-ribosomal peptide synthetases using specific assembly points within condensation domains. Nat. Chem. 2019;11:653–661. doi: 10.1038/s41557-019-0276-z. - DOI - PubMed

LinkOut - more resources