Viennamycins: Lipopeptides Produced by a <i>Streptomyces</i> sp.

Bekiesch, Paulina; Zehl, Martin; Domingo-Contreras, Elizabeth; Martín, Jesús; Pérez-Victoria, Ignacio; Reyes, Fernando; Kaplan, Arthur M.; Rückert, Christian; Busche, Tobias; Kalinowski, Jörn; Zotchev, Sergey B.

doi:10.1021/acs.jnatprod.0c00152

Cited by 20 publications

(18 citation statements)

References 22 publications

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“…Base-calling of the raw data was performed with GUPPY-FOR-GRIDION v3.0.6. The assembly and polishing were performed as described previously, 48 using canu v.1.8 instead of v.1.6. The ONT data was assembled into 5 contigs, while the Illumina data were assembled into 87 scaffolds containing 310 contigs using NEWBLER v2.8.…”

Section: Methodsmentioning

confidence: 99%

Genomic-Led Discovery of a Novel Glycopeptide Antibiotic by Nonomuraea coxensis DSM 45129

et al. 2021

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Glycopeptide antibiotics (GPAs) are last defense line drugs against multidrug-resistant Gram-positive pathogens. Natural GPAs teicoplanin and vancomycin, as well as semisynthetic oritavancin, telavancin, and dalbavancin, are currently approved for clinical use. Although these antibiotics remain efficient, emergence of novel GPA-resistant pathogens is a question of time. Therefore, it is important to investigate the natural variety of GPAs coming from so-called “rare” actinobacteria. Herein we describe a novel GPA producer— Nonomuraea coxensis DSM 45129. Its de novo sequenced and completely assembled genome harbors a biosynthetic gene cluster (BGC) similar to the dbv BGC of A40926, the natural precursor to dalbavancin. The strain produces a novel GPA, which we propose is an A40926 analogue lacking the carboxyl group on the N -acylglucosamine moiety. This structural difference correlates with the absence of dbv29 —coding for an enzyme responsible for the oxidation of the N -acylglucosamine moiety. Introduction of dbv29 into N. coxensis led to A40926 production in this strain. Finally, we successfully applied dbv3 and dbv4 heterologous transcriptional regulators to trigger and improve A50926 production in N. coxensis , making them prospective tools for screening other Nonomuraea spp. for GPA production. Our work highlights genus Nonomuraea as a still untapped source of novel GPAs.

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Section: Methodsmentioning

confidence: 99%

Genomic-Led Discovery of a Novel Glycopeptide Antibiotic by Nonomuraea coxensis DSM 45129

et al. 2021

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“…However, the initial sequence of lcm cluster contained large gaps in the one of the lcm PKS genes, known to be challenging target to sequence due to their highly repetitive nature. Therefore, in this work S. cyanogenus S136 genome was re-sequenced using a combination of HiSeq Illumina and GridION ONT technologies, essentially as described in 78 . Final S136 genome (8773 kbp) was manually curated and annotated using Prokka annotation pipeline 79 .…”

Section: Methodsmentioning

confidence: 99%

Eliciting the silent lucensomycin biosynthetic pathway in Streptomyces cyanogenus S136 via manipulation of the global regulatory gene adpA

Yushchuk

Ostash

Mösker

et al. 2021

Sci Rep

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Actinobacteria are among the most prolific sources of medically and agriculturally important compounds, derived from their biosynthetic gene clusters (BGCs) for specialized (secondary) pathways of metabolism. Genomics witnesses that the majority of actinobacterial BGCs are silent, most likely due to their low or zero transcription. Much effort is put into the search for approaches towards activation of silent BGCs, as this is believed to revitalize the discovery of novel natural products. We hypothesized that the global transcriptional factor AdpA, due to its highly degenerate operator sequence, could be used to upregulate the expression of silent BGCs. Using Streptomyces cyanogenus S136 as a test case, we showed that plasmids expressing either full-length adpA or its DNA-binding domain led to significant changes in the metabolome. These were evident as changes in the accumulation of colored compounds, bioactivity, as well as the emergence of a new pattern of secondary metabolites as revealed by HPLC-ESI-mass spectrometry. We further focused on the most abundant secondary metabolite and identified it as the polyene antibiotic lucensomycin. Finally, we uncovered the entire gene cluster for lucensomycin biosynthesis (lcm), that remained elusive for five decades until now, and outlined an evidence-based scenario for its adpA-mediated activation.

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“…In 2020, ten novel cyclic peptides were reported across seven publications [4,6,[8][9][10][11][12]. The size of the peptide core ranged from two to seven amino acids, though three of these compounds, ulleungamide C (1) [11] and viennamycins A and B (2 and 3) (Figure 4) [8], are depsipeptides, and two more, NOS-V1 (4) and NOS-V2 (5) (Figure 5), possess the typical di-macrocycle composition of a thiopeptide nosiheptide [6]. These compounds originate from both non-ribosomal peptide synthetases (NRPSs) and ribosomal synthesis with post-translational modification.…”

Section: Cyclic Peptidesmentioning

confidence: 99%

Recently Discovered Secondary Metabolites from Streptomyces Species

Lacey

Rutledge

2022

Molecules

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The Streptomyces genus has been a rich source of bioactive natural products, medicinal chemicals, and novel drug leads for three-quarters of a century. Yet studies suggest that the genus is capable of making some 150,000 more bioactive compounds than all Streptomyces secondary metabolites reported to date. Researchers around the world continue to explore this enormous potential using a range of strategies including modification of culture conditions, bioinformatics and genome mining, heterologous expression, and other approaches to cryptic biosynthetic gene cluster activation. Our survey of the recent literature, with a particular focus on the year 2020, brings together more than 70 novel secondary metabolites from Streptomyces species, which are discussed in this review. This diverse array includes cyclic and linear peptides, peptide derivatives, polyketides, terpenoids, polyaromatics, macrocycles, and furans, the isolation, chemical structures, and bioactivity of which are appraised. The discovery of these many different compounds demonstrates the continued potential of Streptomyces as a source of new and interesting natural products and contributes further important pieces to the mostly unfinished puzzle of Earth’s myriad microbes and their multifaceted chemical output.

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Viennamycins: Lipopeptides Produced by a Streptomyces sp.

Cited by 20 publications

References 22 publications

Genomic-Led Discovery of a Novel Glycopeptide Antibiotic by Nonomuraea coxensis DSM 45129

Genomic-Led Discovery of a Novel Glycopeptide Antibiotic by Nonomuraea coxensis DSM 45129

Eliciting the silent lucensomycin biosynthetic pathway in Streptomyces cyanogenus S136 via manipulation of the global regulatory gene adpA

Recently Discovered Secondary Metabolites from Streptomyces Species

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