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Marine Drugs
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Microbial Gene Clusters of Marine Origin
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Microbial Gene Clusters of Marine Origin

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

Deadline for manuscript submissions: closed (30 October 2018) | Viewed by 35736

Special Issue Editors

Prof. Dr. Jose A. Salas

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Guest Editor
Department of Functional Biology (Area Microbiology), Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain
Interests: bioactive natural products; anticancer agents; antimicrobial agents; biosynthesis; polyketides; nonribosomal peptides; glycosylated compounds
Special Issues, Collections and Topics in MDPI journals
Dr. Carlos Olano

E-Mail Website
Guest Editor
Department of Functional Biology (Area Microbiology), Faculty of Medicine, University of Oviedo, 33006 Oviedo, Spain
Interests: bioactive natural products; anticancer agents; antimicrobial agents; biosynthesis; polyketides; nonribosomal peptides; glycosylated compounds

Special Issue Information

Dear Colleagues,

Free-living or symbiotic marine microorganisms have been  recognized as an important source for the production of novel bioactive compounds with different biotechnological applications (i.e., medicine, cosmetics, agriculture, etc). Many of these compounds show complex chemical structures, and their biosynthesis is encoded by gene clusters that are normally located in their chromosomes. This Special Issue will cover different aspects related to gene clusters involved in the biosynthesis of secondary metabolites by marine microorganism, such as (i) genome mining of marine microorganisms for the identification of gene clusters; (ii) characterization of gene clusters and proofs of the involvement of the cluster in the biosynthesis of a particular compound; (iii) activation of silent or poorly expressed clusters; (iv) studies on gene expression of clusters in  marine microorganisms; (v) heterologous expression of marine gene clusters; and (v) generation of novel derivatives by genetic engineering. Other topics related to those mentioned above may also be considered.

Prof. Dr. Jose Salas
Dr. Carlos Olano
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Marine Drugs is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Bioactive compounds
  • Polyketides
  • Nonribosomal peptides
  • Secondary metabolites
  • Genome mining

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Related Special Issue

Published Papers (6 papers)

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Research

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10 pages, 2236 KiB  
Communication
Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108
by Marta Rodríguez Estévez, Maksym Myronovskyi, Nils Gummerlich, Suvd Nadmid and Andriy Luzhetskyy
Mar. Drugs 2018, 16(11), 435; https://doi.org/10.3390/md16110435 - 4 Nov 2018
Cited by 22 | Viewed by 5731
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
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18 pages, 1945 KiB  
Article
Characterization of the Jomthonic Acids Biosynthesis Pathway and Isolation of Novel Analogues in Streptomyces caniferus GUA-06-05-006A
by Raúl García-Salcedo, Rubén Álvarez-Álvarez, Carlos Olano, Librada Cañedo, Alfredo F. Braña, Carmen Méndez, Fernando De la Calle and José A. Salas
Mar. Drugs 2018, 16(8), 259; https://doi.org/10.3390/md16080259 - 31 Jul 2018
Cited by 13 | Viewed by 4701
Abstract
Jomthonic acids (JAs) are a group of natural products (NPs) with adipogenic activity. Structurally, JAs are formed by a modified β-methylphenylalanine residue, whose biosynthesis involves a methyltransferase that in Streptomyces hygroscopicus has been identified as MppJ. Up to date, three JA members (A–C) [...] Read more.
Jomthonic acids (JAs) are a group of natural products (NPs) with adipogenic activity. Structurally, JAs are formed by a modified β-methylphenylalanine residue, whose biosynthesis involves a methyltransferase that in Streptomyces hygroscopicus has been identified as MppJ. Up to date, three JA members (A–C) and a few other natural products containing β-methylphenylalanine have been discovered from soil-derived microorganisms. Herein, we report the identification of a gene (jomM) coding for a putative methyltransferase highly identical to MppJ in the chromosome of the marine actinobacteria Streptomyces caniferus GUA-06-05-006A. In its 5’ region, jomM clusters with two polyketide synthases (PKS) (jomP1, jomP2), a nonribosomal peptide synthetase (NRPS) (jomN) and a thioesterase gene (jomT), possibly conforming a single transcriptional unit. Insertion of a strong constitutive promoter upstream of jomP1 led to the detection of JA A, along with at least two novel JA family members (D and E). Independent inactivation of jomP1, jomN and jomM abolished production of JA A, JA D and JA E, indicating the involvement of these genes in JA biosynthesis. Heterologous expression of the JA biosynthesis cluster in Streptomyces coelicolor M1152 and in Streptomyces albus J1074 led to the production of JA A, B, C and F. We propose a pathway for JAs biosynthesis based on the findings here described. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
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8 pages, 1625 KiB  
Article
Heterologous Expression of a VioA Variant Activates Cryptic Compounds in a Marine-Derived Brevibacterium Strain
by Xiao Han, Lukuan Hou, Jing Hou, Yongyu Zhang, Huayue Li and Wenli Li
Mar. Drugs 2018, 16(6), 191; https://doi.org/10.3390/md16060191 - 2 Jun 2018
Cited by 3 | Viewed by 4236
Abstract
A new 14-membered homodimeric macrodiolide, brevidiolide (3), along with four known aromatic compounds (1, 2, 4 and 5) were obtained by heterologous expression of the recombinant plasmid pWLI823 expressing the G231L variant of VioA in the marine-derived [...] Read more.
A new 14-membered homodimeric macrodiolide, brevidiolide (3), along with four known aromatic compounds (1, 2, 4 and 5) were obtained by heterologous expression of the recombinant plasmid pWLI823 expressing the G231L variant of VioA in the marine-derived Brevibacterium sp. 7002-073. The structures of 1–5 were elucidated on the basis of LC-MS and 2D NMR spectroscopic analyses. In the evaluation for the antibacterial activities of the compounds against multi-drug resistant (MDR) strains, 5 showed notable growth inhibition against Staphylococcus aureus CCARM 3090 and Klebsiella pneumoniae ATCC 13883, with a minimum inhibitory concentration (MIC) value of 3.12 µg/mL. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
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12 pages, 2155 KiB  
Article
Identification and Characterization of Mycemycin Biosynthetic Gene Clusters in Streptomyces olivaceus FXJ8.012 and Streptomyces sp. FXJ1.235
by Fangying Song, Ning Liu, Minghao Liu, Yihua Chen and Ying Huang
Mar. Drugs 2018, 16(3), 98; https://doi.org/10.3390/md16030098 - 20 Mar 2018
Cited by 6 | Viewed by 5834
Abstract
Mycemycins A–E are new members of the dibenzoxazepinone (DBP) family, derived from the gntR gene-disrupted deep sea strain Streptomyces olivaceus FXJ8.012Δ1741 and the soil strain Streptomyces sp. FXJ1.235. In this paper, we report the identification of the gene clusters and pathways’ inference for [...] Read more.
Mycemycins A–E are new members of the dibenzoxazepinone (DBP) family, derived from the gntR gene-disrupted deep sea strain Streptomyces olivaceus FXJ8.012Δ1741 and the soil strain Streptomyces sp. FXJ1.235. In this paper, we report the identification of the gene clusters and pathways’ inference for mycemycin biosynthesis in the two strains. Bioinformatics analyses of the genome sequences of S. olivaceus FXJ8.012Δ1741 and S. sp. FXJ1.235 predicted two divergent mycemycin gene clusters, mym and mye, respectively. Heterologous expression of the key enzyme genes of mym and genetic manipulation of mye as well as a feeding study in S. sp. FXJ1.235 confirmed the gene clusters and led to the proposed biosynthetic pathways for mycemycins. To the best of our knowledge, this is the first report on DBP biosynthetic gene clusters and pathways. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
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18 pages, 1503 KiB  
Article
Diverse and Abundant Secondary Metabolism Biosynthetic Gene Clusters in the Genomes of Marine Sponge Derived Streptomyces spp. Isolates
by Stephen A. Jackson, Lisa Crossman, Eduardo L. Almeida, Lekha Menon Margassery, Jonathan Kennedy and Alan D.W. Dobson
Mar. Drugs 2018, 16(2), 67; https://doi.org/10.3390/md16020067 - 20 Feb 2018
Cited by 57 | Viewed by 8905
Abstract
The genus Streptomyces produces secondary metabolic compounds that are rich in biological activity. Many of these compounds are genetically encoded by large secondary metabolism biosynthetic gene clusters (smBGCs) such as polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) which are modular and can [...] Read more.
The genus Streptomyces produces secondary metabolic compounds that are rich in biological activity. Many of these compounds are genetically encoded by large secondary metabolism biosynthetic gene clusters (smBGCs) such as polyketide synthases (PKS) and non-ribosomal peptide synthetases (NRPS) which are modular and can be highly repetitive. Due to the repeats, these gene clusters can be difficult to resolve using short read next generation datasets and are often quite poorly predicted using standard approaches. We have sequenced the genomes of 13 Streptomyces spp. strains isolated from shallow water and deep-sea sponges that display antimicrobial activities against a number of clinically relevant bacterial and yeast species. Draft genomes have been assembled and smBGCs have been identified using the antiSMASH (antibiotics and Secondary Metabolite Analysis Shell) web platform. We have compared the smBGCs amongst strains in the search for novel sequences conferring the potential to produce novel bioactive secondary metabolites. The strains in this study recruit to four distinct clades within the genus Streptomyces. The marine strains host abundant smBGCs which encode polyketides, NRPS, siderophores, bacteriocins and lantipeptides. The deep-sea strains appear to be enriched with gene clusters encoding NRPS. Marine adaptations are evident in the sponge-derived strains which are enriched for genes involved in the biosynthesis and transport of compatible solutes and for heat-shock proteins. Streptomyces spp. from marine environments are a promising source of novel bioactive secondary metabolites as the abundance and diversity of smBGCs show high degrees of novelty. Sponge derived Streptomyces spp. isolates appear to display genomic adaptations to marine living when compared to terrestrial strains. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
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Review

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21 pages, 1480 KiB  
Review
Harnessing Marine Biocatalytic Reservoirs for Green Chemistry Applications through Metagenomic Technologies
by Ignacio Abreu Castilla, David F. Woods, F. Jerry Reen and Fergal O’Gara
Mar. Drugs 2018, 16(7), 227; https://doi.org/10.3390/md16070227 - 4 Jul 2018
Cited by 20 | Viewed by 5648
Abstract
In a demanding commercial world, large-scale chemical processes have been widely utilised to satisfy consumer related needs. Chemical industries are key to promoting economic growth and meeting the requirements of a sustainable industrialised society. The market need for diverse commodities produced by the [...] Read more.
In a demanding commercial world, large-scale chemical processes have been widely utilised to satisfy consumer related needs. Chemical industries are key to promoting economic growth and meeting the requirements of a sustainable industrialised society. The market need for diverse commodities produced by the chemical industry is rapidly expanding globally. Accompanying this demand is an increased threat to the environment and to human health, due to waste produced by increased industrial production. This increased demand has underscored the necessity to increase reaction efficiencies, in order to reduce costs and increase profits. The discovery of novel biocatalysts is a key method aimed at combating these difficulties. Metagenomic technology, as a tool for uncovering novel biocatalysts, has great potential and applicability and has already delivered many successful achievements. In this review we discuss, recent developments and achievements in the field of biocatalysis. We highlight how green chemistry principles through the application of biocatalysis, can be successfully promoted and implemented in various industrial sectors. In addition, we demonstrate how two novel lipases/esterases were mined from the marine environment by metagenomic analysis. Collectively these improvements can result in increased efficiency, decreased energy consumption, reduced waste and cost savings for the chemical industry. Full article
(This article belongs to the Special Issue Microbial Gene Clusters of Marine Origin)
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