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. 2021 Jul 31;9(8):1640.
doi: 10.3390/microorganisms9081640.

Bonsecamin: A New Cyclic Pentapeptide Discovered through Heterologous Expression of a Cryptic Gene Cluster

Constanze Lasch  1 , Marc Stierhof  1 , Marta Rodríguez Estévez  1 , Maksym Myronovskyi  1 , Josef Zapp  2 , Andriy Luzhetskyy  1   3
Affiliations

Bonsecamin: A New Cyclic Pentapeptide Discovered through Heterologous Expression of a Cryptic Gene Cluster

Constanze Lasch et al. Microorganisms. .

Abstract

The intriguing structural complexity of molecules produced by natural organisms is uncontested. Natural scaffolds serve as an important basis for the development of molecules with broad applications, e.g., therapeutics or agrochemicals. Research in recent decades has demonstrated that by means of classic metabolite extraction from microbes only a small portion of natural products can be accessed. The use of genome mining and heterologous expression approaches represents a promising way to discover new natural compounds. In this paper we report the discovery of a novel cyclic pentapeptide called bonsecamin through the heterologous expression of a cryptic NRPS gene cluster from Streptomyces albus ssp. chlorinus NRRL B-24108 in Streptomyces albus Del14. The new compound was successfully isolated and structurally characterized using NMR. The minimal set of genes required for bonsecamin production was determined through bioinformatic analysis and gene deletion experiments. A biosynthetic route leading to the production of bonsecamin is proposed in this paper.

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

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
General workflow for compound discovery using heterologous expression.
Figure 2
Figure 2
HPLC-MS analysis of bonsecamin production. A- and B-extracted ion chromatograms (430.5 ± 0.5 Da) of crude extracts of S. albus 2O18 and S. albus Del14, respectively. The new peak observed in the extract of S. albus 2O18 is marked with an asterisk (*). C–Mass spectrum of the new peak observed in the extract of S. albus 2O18.
Figure 3
Figure 3
The structure of isolated bonsecamin.
Figure 4
Figure 4
Fragment of the Streptomyces albus ssp. chlorinus NRRL B-24108 chromosome cloned in BAC 2O18. The genes putatively involved in bonsecamin biosynthesis are highlighted in dark grey. The black bars indicate the chromosomal fragments cloned in BACs 2O18, 2O18_del1 and 2O18_del2 [29].
Figure 5
Figure 5
Proposed biosynthetic scheme for bonsecamin production. A. Formation of the Ala-Ala-Val tripeptide precursor catalyzed by the putative alanine ligase encoded by bonG. B. Conversion of the tripeptide intermediate into the linear pentapeptide precursor catalyzed by the NRPS encoded by bonB, bonF and bonC. C. Cyclization of the linear bonsecamin precursor catalyzed by the products of bonE and bonD.
See this image and copyright information in PMC

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