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 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.

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 Overproduction of Ristomycin A by Activation of a Silent Gene Cluster in Amycolatopsis japonicum MG417-CF17

2014 ◽  
Vol 58 (10) ◽  
pp. 6185-6196 ◽  
Author(s):  
Marius Spohn ◽  
Norbert Kirchner ◽  
Andreas Kulik ◽  
Angelika Jochim ◽  
Felix Wolf ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gene Cluster ◽  
High Performance ◽  
Pathogenic Bacteria ◽  
Genome Mining ◽  
Gene Clusters ◽  
Von Willebrand Disease ◽  
Biosynthesis Gene Cluster ◽  
Content Type ◽  
Bioinformatic Tools

ABSTRACTThe emergence of antibiotic-resistant pathogenic bacteria within the last decades is one reason for the urgent need for new antibacterial agents. A strategy to discover new anti-infective compounds is the evaluation of the genetic capacity of secondary metabolite producers and the activation of cryptic gene clusters (genome mining). One genus known for its potential to synthesize medically important products isAmycolatopsis. However,Amycolatopsis japonicumdoes not produce an antibiotic under standard laboratory conditions. In contrast to mostAmycolatopsisstrains,A. japonicumis genetically tractable with different methods. In order to activate a possible silent glycopeptide cluster, we introduced a gene encoding the transcriptional activator of balhimycin biosynthesis, thebbrgene fromAmycolatopsis balhimycina(bbrAba), intoA. japonicum. This resulted in the production of an antibiotically active compound. Following whole-genome sequencing ofA. japonicum, 29 cryptic gene clusters were identified by genome mining. One of these gene clusters is a putative glycopeptide biosynthesis gene cluster. Using bioinformatic tools, ristomycin (syn. ristocetin), a type III glycopeptide, which has antibacterial activity and which is used for the diagnosis of von Willebrand disease and Bernard-Soulier syndrome, was deduced as a possible product of the gene cluster. Chemical analyses by high-performance liquid chromatography and mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS), and nuclear magnetic resonance (NMR) spectroscopy confirmed thein silicoprediction that the recombinantA. japonicum/pRM4-bbrAbasynthesizes ristomycin A.

scholarly journals Engineering the Erythromycin-Producing Strain Saccharopolyspora erythraea HOE107 for the Heterologous Production of Polyketide Antibiotics

2020 ◽  
Vol 11 ◽  
Author(s):  
Jin Lü ◽  
Qingshan Long ◽  
Zhilong Zhao ◽  
Lu Chen ◽  
Weijun He ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Polyketide Synthase ◽  
Streptomyces Coelicolor ◽  
Genome Mining ◽  
Bac Library ◽  
Gene Clusters ◽  
Artificial Chromosome ◽  
Saccharopolyspora Erythraea ◽  
Heterologous Production ◽  
Integration Sites

Bacteria of the genus Saccharopolyspora produce important polyketide antibiotics, including erythromycin A (Sac. erythraea) and spinosad (Sac. spinosa). We herein report the development of an industrial erythromycin-producing strain, Sac. erythraea HOE107, into a host for the heterologous expression of polyketide biosynthetic gene clusters (BGCs) from other Saccharopolyspora species and related actinomycetes. To facilitate the integration of natural product BGCs and auxiliary genes beneficial for the production of natural products, the erythromycin polyketide synthase (ery) genes were replaced with two bacterial attB genomic integration sites associated with bacteriophages ϕC31 and ϕBT1. We also established a highly efficient conjugation protocol for the introduction of large bacterial artificial chromosome (BAC) clones into Sac. erythraea strains. Based on this optimized protocol, an arrayed BAC library was effectively transferred into Sac. erythraea. The large spinosad gene cluster from Sac. spinosa and the actinorhodin gene cluster from Streptomyces coelicolor were successfully expressed in the ery deletion mutant. Deletion of the endogenous giant polyketide synthase genes pkeA1-pkeA4, the product of which is not known, and the flaviolin gene cluster (rpp) from the bacterium increased the heterologous production of spinosad and actinorhodin. Furthermore, integration of pJTU6728 carrying additional beneficial genes dramatically improved the yield of actinorhodin in the engineered Sac. erythraea strains. Our study demonstrated that the engineered Sac. erythraea strains SLQ185, LJ161, and LJ162 are good hosts for the expression of heterologous antibiotics and should aid in expression-based genome-mining approaches for the discovery of new and cryptic antibiotics from Streptomyces and rare actinomycetes.

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

scholarly journals Bioactivity-Guided Genome Mining Reveals the Lomaiviticin Biosynthetic Gene Cluster inSalinispora tropica

ChemBioChem ◽  
2013 ◽  
Vol 14 (8) ◽  
pp. 955-962 ◽  
Author(s):  
Roland D. Kersten ◽  
Amy L. Lane ◽  
Markus Nett ◽  
Taylor K. S. Richter ◽  
Brendan M. Duggan ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene

scholarly journals MS/MS-based networking and peptidogenomics guided genome mining revealed the stenothricin gene cluster in Streptomyces roseosporus

2013 ◽  
Vol 67 (1) ◽  
pp. 99-104 ◽  
Author(s):  
Wei-Ting Liu ◽  
Anne Lamsa ◽  
Weng Ruh Wong ◽  
Paul D Boudreau ◽  
Roland Kersten ◽  
...  
Keyword(s):  
Gene Cluster ◽  
Genome Mining ◽  
Streptomyces Roseosporus

scholarly journals Correction: Genome mining and molecular characterization of the biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in Penicillium canescens

2016 ◽  
Vol 7 (3) ◽  
pp. 2440-2440 ◽  
Author(s):  
Junko Yaegashi ◽  
Jillian Romsdahl ◽  
Yi-Ming Chiang ◽  
Clay C. C. Wang
Keyword(s):  
Gene Cluster ◽  
Molecular Characterization ◽  
Genome Mining ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Penicillium Canescens

Correction for ‘Genome mining and molecular characterization of the biosynthetic gene cluster of a diterpenic meroterpenoid, 15-deoxyoxalicine B, in Penicillium canescens’ by Junko Yaegashi et al., Chem. Sci., 2015, 6, 6537–6544.

Genome mining approach for harnessing the cryptic gene cluster in Alternaria solani: production of PKS–NRPS hybrid metabolite, didymellamide B

2016 ◽  
Vol 57 (25) ◽  
pp. 2793-2796 ◽  
Author(s):  
Takahiro Ugai ◽  
Atsushi Minami ◽  
Katsuya Gomi ◽  
Hideaki Oikawa
Keyword(s):  
Gene Cluster ◽  
Genome Mining ◽  
Alternaria Solani
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