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

2021 ◽  
Vol 9 (8) ◽  
pp. 1640
Author(s):  
Constanze Lasch ◽  
Marc Stierhof ◽  
Marta Rodríguez Estévez ◽  
Maksym Myronovskyi ◽  
Josef Zapp ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Gene Deletion ◽  
Genome Mining ◽  
Structural Complexity ◽  
Bioinformatic Analysis ◽  
Nrps Gene ◽  
Minimal Set ◽  
Streptomyces Albus ◽  
Important Basis

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.

scholarly journals Identification and Heterologous Expression of the Albucidin Gene Cluster from the Marine Strain Streptomyces Albus Subsp. Chlorinus NRRL B-24108

2020 ◽  
Vol 8 (2) ◽  
pp. 237 ◽  
Author(s):  
Maksym Myronovskyi ◽  
Birgit Rosenkränzer ◽  
Marc Stierhof ◽  
Lutz Petzke ◽  
Tobias Seiser ◽  
...  
Keyword(s):  
Biological Activity ◽  
Heterologous Expression ◽  
Gene Cluster ◽  
Gene Annotation ◽  
Structural Diversity ◽  
Minimal Set ◽  
Streptomyces Albus ◽  
Marine Strain ◽  
Promising Source ◽  
Producer Strains

Herbicides with new modes of action and safer toxicological and environmental profiles are needed to manage the evolution of weeds that are resistant to commercial herbicides. The unparalleled structural diversity of natural products makes these compounds a promising source for new herbicides. In 2009, a novel nucleoside phytotoxin, albucidin, with broad activity against grass and broadleaf weeds was isolated from a strain of Streptomyces albus subsp. chlorinus NRRL B-24108. Here, we report the identification and heterologous expression of the previously uncharacterized albucidin gene cluster. Through a series of gene inactivation experiments, a minimal set of albucidin biosynthetic genes was determined. Based on gene annotation and sequence homology, a model for albucidin biosynthesis was suggested. The presented results enable the construction of producer strains for a sustainable supply of albucidin for biological activity studies.

scholarly journals Comparative genome mining and heterologous expression of an orphan NRPS gene cluster direct the production of ashimides

2019 ◽  
Vol 10 (10) ◽  
pp. 3042-3048 ◽  
Author(s):  
Jing Shi ◽  
Ying Jie Zeng ◽  
Bo Zhang ◽  
Fen Li Shao ◽  
Yan Chi Chen ◽  
...  
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Genome Mining ◽  
Nrps Gene ◽  
Comparative Genome

Genome mining and heterologous expression of an orphan cluster led to the discovery of ashimides featuring an unusual cyclization mechanism.

Heterologous expression of an orphan NRPS gene cluster from Paenibacillus larvae in Escherichia coli revealed production of sevadicin

2015 ◽  
Vol 194 ◽  
pp. 112-114 ◽  
Author(s):  
Ying Tang ◽  
Simon Frewert ◽  
Kirsten Harmrolfs ◽  
Jennifer Herrmann ◽  
Lisa Karmann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Heterologous Expression ◽  
Gene Cluster ◽  
Paenibacillus Larvae ◽  
Nrps Gene

Dissecting tunicamycin biosynthesis by genome mining: cloning and heterologous expression of a minimal gene cluster

2010 ◽  
Vol 1 (5) ◽  
pp. 581 ◽  
Author(s):  
Filip J. Wyszynski ◽  
Andrew R. Hesketh ◽  
Mervyn J. Bibb ◽  
Benjamin G. Davis
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Genome Mining

Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides

2017 ◽  
Vol 19 (20) ◽  
pp. 5697-5700 ◽  
Author(s):  
Ruidong Chen ◽  
Qingbo Zhang ◽  
Bin Tan ◽  
Liujuan Zheng ◽  
Huixian Li ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Genome Mining ◽  
Nrps Gene

scholarly journals Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108

Marine Drugs ◽  
2018 ◽  
Vol 16 (11) ◽  
pp. 435 ◽  
Author(s):  
Marta Rodríguez Estévez ◽  
Maksym Myronovskyi ◽  
Nils Gummerlich ◽  
Suvd Nadmid ◽  
Andriy Luzhetskyy
Keyword(s):  
Heterologous Expression ◽  
Gene Cluster ◽  
Gene Clusters ◽  
Growth Conditions ◽  
Pharmaceutical Drugs ◽  
Gyra Gene ◽  
Streptomyces Albus ◽  
Potential Applications ◽  
Resistant Mutants ◽  
Marine Strain

Streptomycetes represent an important reservoir of active secondary metabolites with potential applications in the pharmaceutical industry. The gene clusters responsible for their production are often cryptic under laboratory growth conditions. Characterization of these clusters is therefore essential for the discovery of new microbial pharmaceutical drugs. Here, we report the identification of the previously uncharacterized nybomycin gene cluster from the marine actinomycete Streptomyces albus subsp. chlorinus through its heterologous expression. Nybomycin has previously been reported to act against quinolone-resistant Staphylococcus aureus strains harboring a mutated gyrA gene but not against those with intact gyrA. The nybomycin-resistant mutants generated from quinolone-resistant mutants have been reported to be caused by a back-mutation in the gyrA gene that restores susceptibility to quinolones. On the basis of gene function assignment from bioinformatics analysis, we suggest a model for nybomycin biosynthesis.

scholarly journals Identification of a Biosynthetic Gene Cluster Responsible for the Production of a New Pyrrolopyrimidine Natural Product—Huimycin

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1074
Author(s):  
Hui Shuai ◽  
Maksym Myronovskyi ◽  
Suvd Nadmid ◽  
Andriy Luzhetskyy
Keyword(s):  
Gene Cluster ◽  
Gene Deletion ◽  
Biological Activities ◽  
Biosynthetic Gene Cluster ◽  
Resonance Spectroscopy ◽  
Important Class ◽  
Biosynthetic Gene ◽  
Heterologous Host ◽  
Streptomyces Albus ◽  
Actinomycete Strain

Pyrrolopyrimidines are an important class of natural products with a broad spectrum of biological activities, including antibacterial, antifungal, antiviral, anticancer or anti-inflammatory. Here, we present the identification of a biosynthetic gene cluster from the rare actinomycete strain Kutzneria albida DSM 43870, which leads to the production of huimycin, a new member of the pyrrolopyrimidine family of compounds. The huimycin gene cluster was successfully expressed in the heterologous host strain Streptomyces albus Del14. The compound was purified, and its structure was elucidated by means of nuclear magnetic resonance spectroscopy. The minimal huimycin gene cluster was identified through sequence analysis and a series of gene deletion experiments. A model for huimycin biosynthesis is also proposed in this paper.

scholarly journals Cyclofaulknamycin with the Rare Amino Acid D-capreomycidine Isolated from a Well-Characterized Streptomyces albus Strain

2021 ◽  
Vol 9 (8) ◽  
pp. 1609
Author(s):  
Liliya Horbal ◽  
Marc Stierhof ◽  
Anja Palusczak ◽  
Nikolas Eckert ◽  
Josef Zapp ◽  
...  
Keyword(s):  
Amino Acid ◽  
Gene Cluster ◽  
Pyridoxal Phosphate ◽  
Cyclic Peptide ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Streptomyces Albus ◽  
Cluster Biosynthesis ◽  
First Time

Targeted genome mining is an efficient method of biosynthetic gene cluster prioritization within constantly growing genome databases. Using two capreomycidine biosynthesis genes, alpha-ketoglutarate-dependent arginine beta-hydroxylase and pyridoxal-phosphate-dependent aminotransferase, we identified two types of clusters: one type containing both genes involved in the biosynthesis of the abovementioned moiety, and other clusters including only arginine hydroxylase. Detailed analysis of one of the clusters, the flk cluster from Streptomyces albus, led to the identification of a cyclic peptide that contains a rare D-capreomycidine moiety for the first time. The absence of the pyridoxal-phosphate-dependent aminotransferase gene in the flk cluster is compensated by the XNR_1347 gene in the S. albus genome, whose product is responsible for biosynthesis of the abovementioned nonproteinogenic amino acid. Herein, we report the structure of cyclofaulknamycin and the characteristics of its biosynthetic gene cluster, biosynthesis and bioactivity profile.

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