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Molecules
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Genomics-based Discovery of Microbial Natural Products
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Genomics-based Discovery of Microbial Natural Products

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (20 October 2016) | Viewed by 15277

Special Issue Editor

Prof. Dr. Sergey Zotchev

E-Mail Website
Guest Editor
Department of Pharmacognosy, University of Vienna, Vienna, Austria
Interests: antibiotics; bioprospecting; secondary metabolites biosynthesis; bacterial genetics; metabolic engineering; synthetic biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Natural products from microorganisms have been an invaluable resource and an inspiration for drug discovery for decades. However, natural product-based drug discovery has been in decline over the last 20 years. This was mainly due to frequent re-discovery of already known compounds, our limited ability to cultivate certain microbial isolates, and/or to exploit full genetic capacity of the microbes to synthesize natural products. At the same time, in recent years, a large number of microbial genomes have been sequenced, revealing an enormous hidden capacity for biosynthesis of potentially novel molecules that can be used in drug discovery programs. Thousands of the so-called “orphan” biosynthetic gene clusters have been revealed, for which no associated natural products have been reported so far. This Special Issue aims to provide the most recent information regarding genomics-based strategies and methodologies directed to the discovery, analyses, activation, heterologous expression and manipulation of the “orphan” biosynthetic gene clusters, as well as pleiotropic regulators generally affecting secondary metabolism.

Prof. Dr. Sergey B. Zotchev
Guest Editor

Manuscript Submission Information

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Keywords

  • Genome-based bioprospecting
  • Natural products
  • Biosynthetic pathways
  • Bioinformatics
  • Genomics
  • Orphan gene clusters
  • Pleiotropic regulators
  • Synthetic biology

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Published Papers (2 papers)

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Research

2426 KiB  
Article
The Draft Genome Sequence of Actinokineospora bangkokensis 44EHWT Reveals the Biosynthetic Pathway of the Antifungal Thailandin Compounds with Unusual Butylmalonyl-CoA Extender Units
by Anja Greule, Bungonsiri Intra, Stephan Flemming, Marcel G. E. Rommel, Watanalai Panbangred and Andreas Bechthold
Molecules 2016, 21(11), 1607; https://doi.org/10.3390/molecules21111607 - 23 Nov 2016
Cited by 5 | Viewed by 7424
Abstract
We report the draft genome sequence of Actinokineospora bangkokensis 44EHWT, the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There [...] Read more.
We report the draft genome sequence of Actinokineospora bangkokensis 44EHWT, the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There are three gene clusters encoding large polyketide synthases of type I. Annotation of the ORF functions and targeted gene disruption enabled us to identify the cluster for thailandin biosynthesis. We propose a plausible biosynthetic pathway for thailandin, where the unusual butylmalonyl-CoA extender unit is incorporated and results in an untypical side chain. Full article
(This article belongs to the Special Issue Genomics-based Discovery of Microbial Natural Products)
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1016 KiB  
Article
New Deferoxamine Glycoconjugates Produced upon Overexpression of Pathway-Specific Regulatory Gene in the Marine Sponge-Derived Streptomyces albus PVA94-07
by Olga N. Sekurova, Ignacio Pérez-Victoria, Jesús Martín, Kristin F. Degnes, Håvard Sletta, Fernando Reyes and Sergey B. Zotchev
Molecules 2016, 21(9), 1131; https://doi.org/10.3390/molecules21091131 - 27 Aug 2016
Cited by 9 | Viewed by 7263
Abstract
Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine [...] Read more.
Activation of silent biosynthetic gene clusters in Streptomyces bacteria via overexpression of cluster-specific regulatory genes is a promising strategy for the discovery of novel bioactive secondary metabolites. This approach was used in an attempt to activate a cryptic gene cluster in a marine sponge-derived Streptomyces albus PVA94-07 presumably governing the biosynthesis of peptide-based secondary metabolites. While no new peptide-based metabolites were detected in the recombinant strain, it was shown to produce at least four new analogues of deferoxamine with additional acyl and sugar moieties, for which chemical structures were fully elucidated. Biological activity tests of two of the new deferoxamine analogues revealed weak activity against Escherichia coli. The gene knockout experiment in the gene cluster targeted for activation, as well as overexpression of certain genes from this cluster did not have an effect on the production of these compounds by the strain overexpressing the regulator. It seems plausible that the production of such compounds is a response to stress imposed by the production of an as-yet unidentified metabolite specified by the cryptic cluster. Full article
(This article belongs to the Special Issue Genomics-based Discovery of Microbial Natural Products)
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