Connecting Marine Microbial Natural Products to Biosynthetic Pathways

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 May 2017) | Viewed by 32699

Special Issue Editors


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Guest Editor
Division of Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Connecticut, 69 N. Eagleville Rd. Unit 3092, Storrs, CT 06231, USA
Interests: marine microbes; natural products chemistry; host-microbe symbioses; antimicrobial and anticancer drug discovery; chemical ecology

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Guest Editor
Department of Chemistry, University of North Florida, 1 UNF Dr., Jacksonville, FL 32224, USA
Interests: marine natural products; biosynthesis; chemical ecology; actinomycetes; polyketides; indole alkaloids; nonribosomal peptides

Special Issue Information

Dear Colleagues,

The recent surge in genome sequencing has illuminated the genetically encoded capabilities of microorganisms to assemble natural products. These efforts have shown that marine microorganisms offer immense potential as producers of biologically active, structurally intriguing molecules underpinned by equally fascinating biosynthetic pathways. The merger of natural product structures with biosynthetic knowledge provides opportunities for advancement of fields including chemical ecology and medicinal chemistry.

This Special Issue focuses on linking marine microbial natural product structures with their biosynthetic origins. Articles will highlight how the merger of these research areas facilitates advancements in fundamental understanding of marine natural products, as well as applications of this knowledge in medicine, agriculture, and other fields.

Prof. Dr. Marcy J. Balunas
Prof. Dr. Amy L. Lane
Guest Editors

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Keywords

  • marine microbial natural products
  • biosynthetic pathways
  • genomics
  • polyketides
  • nonribosomal peptides
  • isoprenes/terpenes
  • structure elucidation
  • marine cyanobacteria
  • marine bacteria
  • marine fungi

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Published Papers (4 papers)

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Research

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1057 KiB  
Article
Upregulation and Identification of Antibiotic Activity of a Marine-Derived Streptomyces sp. via Co-Cultures with Human Pathogens
by Anne A. Sung, Samantha M. Gromek and Marcy J. Balunas
Mar. Drugs 2017, 15(8), 250; https://doi.org/10.3390/md15080250 - 11 Aug 2017
Cited by 56 | Viewed by 8902
Abstract
Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, [...] Read more.
Marine natural product drug discovery has begun to play an important role in the treatment of disease, with several recently approved drugs. In addition, numerous microbial natural products have been discovered from members of the order Actinomycetales, particularly in the genus Streptomyces, due to their metabolic diversity for production of biologically active secondary metabolites. However, many secondary metabolites cannot be produced under laboratory conditions because growth conditions in flask culture differ from conditions in the natural environment. Various experimental conditions (e.g., mixed fermentation) have been attempted to increase yields of previously described metabolites, cause production of previously undetected metabolites, and increase antibiotic activity. Adult ascidians—also known as tunicates—are sessile marine invertebrates, making them vulnerable to predation and therefore are hypothesized to use host-associated bacteria that produce biologically active secondary metabolites for chemical defense. A marine-derived Streptomyces sp. strain PTY087I2 was isolated from a Panamanian tunicate and subsequently co-cultured with human pathogens including Bacillus subtilis, methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa, followed by extraction. Co-culture of Streptomyces sp. PTY087I2 with each of these human pathogens resulted in increased production of three antibiotics: granaticin, granatomycin D, and dihydrogranaticin B, as well as several analogues seen via molecular networking. In addition, co-cultures resulted in strongly enhanced biological activity against the Gram positive human pathogens used in these experiments. Expanded utilization of co-culture experiments to allow for competitive interactions may enhance metabolite production and further our understanding of these microbial interactions. Full article
(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)
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2188 KiB  
Article
Bonnevillamides, Linear Heptapeptides Isolated from a Great Salt Lake-Derived Streptomyces sp.
by Guangwei Wu, Jason R. Nielson, Randall T. Peterson and Jaclyn M. Winter
Mar. Drugs 2017, 15(7), 195; https://doi.org/10.3390/md15070195 - 24 Jun 2017
Cited by 10 | Viewed by 4892
Abstract
Streptomyces sp. GSL-6B was isolated from sediment collected from the Great Salt Lake and investigation of its organic extract led to the isolation of three new linear heptapeptides, bonnevillamides A (1), B (2), and C (3). The [...] Read more.
Streptomyces sp. GSL-6B was isolated from sediment collected from the Great Salt Lake and investigation of its organic extract led to the isolation of three new linear heptapeptides, bonnevillamides A (1), B (2), and C (3). The bonnevillamides represent a new class of linear peptides featuring unprecedented non-proteinogenic amino acids. All three peptides contain the newly characterized bonnevillic acid moiety (3-(3,5-dichloro-4-methoxyphenyl)-2-hydroxyacrylic acid), as well as a heavily modified proline residue. Moreover, in bonnevillamide A, the terminal proline residue found in bonnevillamides B and C is replaced with 4-methyl-azetidine-2-carboxylic acid methyl ester. The structures of the three heptapeptides were elucidated by NMR, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and LC-MS/MS, and the absolute configuration of all proteinogenic amino acid residues were determined by advanced Marfey’s method. Bonnevillamides A, B and C were evaluated for their effects on zebrafish embryo development. All three heptapeptides were shown to modulate heart growth and cardiac function, with bonnevillamide B having the most pronounced effect. Full article
(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)
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Review

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4281 KiB  
Review
Investigating the Biosynthesis of Natural Products from Marine Proteobacteria: A Survey of Molecules and Strategies
by Marshall L. Timmermans, Yagya P. Paudel and Avena C. Ross
Mar. Drugs 2017, 15(8), 235; https://doi.org/10.3390/md15080235 - 1 Aug 2017
Cited by 49 | Viewed by 10304
Abstract
The phylum proteobacteria contains a wide array of Gram-negative marine bacteria. With recent advances in genomic sequencing, genome analysis, and analytical chemistry techniques, a whole host of information is being revealed about the primary and secondary metabolism of marine proteobacteria. This has led [...] Read more.
The phylum proteobacteria contains a wide array of Gram-negative marine bacteria. With recent advances in genomic sequencing, genome analysis, and analytical chemistry techniques, a whole host of information is being revealed about the primary and secondary metabolism of marine proteobacteria. This has led to the discovery of a growing number of medically relevant natural products, including novel leads for the treatment of multidrug-resistant Staphylococcus aureus (MRSA) and cancer. Of equal interest, marine proteobacteria produce natural products whose structure and biosynthetic mechanisms differ from those of their terrestrial and actinobacterial counterparts. Notable features of secondary metabolites produced by marine proteobacteria include halogenation, sulfur-containing heterocycles, non-ribosomal peptides, and polyketides with unusual biosynthetic logic. As advances are made in the technology associated with functional genomics, such as computational sequence analysis, targeted DNA manipulation, and heterologous expression, it has become easier to probe the mechanisms for natural product biosynthesis. This review will focus on genomics driven approaches to understanding the biosynthetic mechanisms for natural products produced by marine proteobacteria. Full article
(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)
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2576 KiB  
Review
Interpreting Microbial Biosynthesis in the Genomic Age: Biological and Practical Considerations
by Ian J. Miller, Marc G. Chevrette and Jason C. Kwan
Mar. Drugs 2017, 15(6), 165; https://doi.org/10.3390/md15060165 - 6 Jun 2017
Cited by 20 | Viewed by 7857
Abstract
Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. [...] Read more.
Genome mining has become an increasingly powerful, scalable, and economically accessible tool for the study of natural product biosynthesis and drug discovery. However, there remain important biological and practical problems that can complicate or obscure biosynthetic analysis in genomic and metagenomic sequencing projects. Here, we focus on limitations of available technology as well as computational and experimental strategies to overcome them. We review the unique challenges and approaches in the study of symbiotic and uncultured systems, as well as those associated with biosynthetic gene cluster (BGC) assembly and product prediction. Finally, to explore sequencing parameters that affect the recovery and contiguity of large and repetitive BGCs assembled de novo, we simulate Illumina and PacBio sequencing of the Salinispora tropica genome focusing on assembly of the salinilactam (slm) BGC. Full article
(This article belongs to the Special Issue Connecting Marine Microbial Natural Products to Biosynthetic Pathways)
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