Genetic Approach and Data Mining in Discovery of Marine Natural Products

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

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 14919

Special Issue Editors


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Guest Editor
Department of Biology, University of Nantes, CNRS, US2B, UMR 6286, F-44000 Nantes, France
Interests: epigenomics; omics; algae; bacteria; ecology; evolution; symbiosis; bioinformatics; biotechnologies
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Guest Editor
Ghent University, Laboratory of Protistology and Aquatic Ecology, Krijgslaan 281, 9000 Gent, Belgium
Interests: microbial ecology and evolution, biogeography, speciation, global change, algal biotechnology

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Guest Editor
Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
Interests: aquaculture; aquatic ecology; biodiversity; biotechnology; genomics; microbiology; bacteria; cultivation; marine microorganisms; probiotics; symbiosis; invertebrates; sponges; deep sea
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Marine-derived bioactive metabolites are gaining attention because of the growing demand due to their benefits and applications in several fields, including pharmaceutical, nutraceutical, cosmetics, and farming. To gain insights into what genes and pathways make these high-value compounds, several studies have sequenced the genomes, transcriptomes, proteomes, and metabolomes of a wide range of species of interest, which had led to an accumulation of a massive amount of data and the discovery of interesting molecules. However, considering the high diversity of species in marine environments compared to land, the discovery of active compounds of marine origin is still in its infancy. Exploring the existing data using computer-aided techniques and genetics is leading to the discovery of new active compounds, and this is likely just the beginning. The objective of this Special Issue is to report some of the recent developments in genetics and data mining fields of multi-omics (genomics, transcriptomics, metabolomics, and proteomics) for drug and active metabolite discovery, including but not only prediction and phylogenomics of metabolic pathways, genome-scale metabolic models, and computer-aided metabolic engineering. This Special Issue is open to marine organisms with a particular focus on micro/macro-algae and bacteria.

Dr. Leila Tirichine
Prof. Dr. Wim Vyverman
Dr. Detmer Sipkema
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

  • Marine active compounds
  • Multi-omics
  • Data mining
  • Genetics
  • Cell factories
  • Genome-scale metabolic models

Published Papers (5 papers)

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Research

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18 pages, 2873 KiB  
Article
Diversity of Bacterial Secondary Metabolite Biosynthetic Gene Clusters in Three Vietnamese Sponges
by Ton That Huu Dat, Georg Steinert, Nguyen Thi Kim Cuc, Pham Viet Cuong, Hauke Smidt and Detmer Sipkema
Mar. Drugs 2023, 21(1), 29; https://doi.org/10.3390/md21010029 - 29 Dec 2022
Cited by 1 | Viewed by 2709
Abstract
Recent reviews have reinforced sponge-associated bacteria as a valuable source of structurally diverse secondary metabolites with potent biological properties, which makes these microbial communities promising sources of new drug candidates. However, the overall diversity of secondary metabolite biosynthetic potential present in bacteria is [...] Read more.
Recent reviews have reinforced sponge-associated bacteria as a valuable source of structurally diverse secondary metabolites with potent biological properties, which makes these microbial communities promising sources of new drug candidates. However, the overall diversity of secondary metabolite biosynthetic potential present in bacteria is difficult to access due to the fact that the majority of bacteria are not readily cultured in the laboratory. Thus, use of cultivation-independent approaches may allow accessing “silent” and “cryptic” secondary metabolite biosynthetic gene clusters present in bacteria that cannot yet be cultured. In the present study, we investigated the diversity of secondary metabolite biosynthetic gene clusters (BGCs) in metagenomes of bacterial communities associated with three sponge species: Clathria reinwardti, Rhabdastrella globostellata, and Spheciospongia sp. The results reveal that the three metagenomes contain a high number of predicted BGCs, ranging from 282 to 463 BGCs per metagenome. The types of BGCs were diverse and represented 12 different cluster types. Clusters predicted to encode fatty acid synthases and polyketide synthases (PKS) were the most dominant BGC types, followed by clusters encoding synthesis of terpenes and bacteriocins. Based on BGC sequence similarity analysis, 363 gene cluster families (GCFs) were identified. Interestingly, no GCFs were assigned to pathways responsible for the production of known compounds, implying that the clusters detected might be responsible for production of several novel compounds. The KS gene sequences from PKS clusters were used to predict the taxonomic origin of the clusters involved. The KS sequences were related to 12 bacterial phyla with Actinobacteria, Proteobacteria, and Firmicutes as the most predominant. At the genus level, the KSs were most related to those found in the genera Mycolicibacterium, Mycobacterium, Burkholderia, and Streptomyces. Phylogenetic analysis of KS sequences resulted in detection of two known ‘sponge-specific’ BGCs, i.e., SupA and SwfA, as well as a new ‘sponge-specific’ cluster related to fatty acid synthesis in the phylum Candidatus Poribacteria and composed only by KS sequences of the three sponge-associated bacterial communities assessed here. Full article
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14 pages, 6317 KiB  
Article
Isolation, Phylogenetic and Gephyromycin Metabolites Characterization of New Exopolysaccharides-Bearing Antarctic Actinobacterium from Feces of Emperor Penguin
by Hui-Min Gao, Peng-Fei Xie, Xiao-Ling Zhang and Qiao Yang
Mar. Drugs 2021, 19(8), 458; https://doi.org/10.3390/md19080458 - 12 Aug 2021
Cited by 7 | Viewed by 2775
Abstract
A new versatile actinobacterium designated as strain NJES-13 was isolated from the feces of the Antarctic emperor penguin. This new isolate was found to produce two active gephyromycin analogues and bioflocculanting exopolysaccharides (EPS) metabolites. Phylogenetic analysis based on pairwise comparison of 16S rRNA [...] Read more.
A new versatile actinobacterium designated as strain NJES-13 was isolated from the feces of the Antarctic emperor penguin. This new isolate was found to produce two active gephyromycin analogues and bioflocculanting exopolysaccharides (EPS) metabolites. Phylogenetic analysis based on pairwise comparison of 16S rRNA gene sequences showed that strain NJES-13 was closely related to Mobilicoccus pelagius Aji5-31T with a gene similarity of 95.9%, which was lower than the threshold value (98.65%) for novel species delineation. Additional phylogenomic calculations of the average nucleotide identity (ANI, 75.9–79.1%), average amino acid identity (AAI, 52.4–66.9%) and digital DNA–DNA hybridization (dDDH, 18.6–21.9%), along with the constructed phylogenomic tree based on the up-to-date bacterial core gene (UBCG) set from the bacterial genomes, unequivocally separated strain NJES-13 from its close relatives within the family Dermatophilaceae. Hence, it clearly indicated that strain NJES-13 represented a putative new actinobacterial species isolated from the gut microbiota of mammals inhabiting the Antarctic. The obtained complete genome of strain NJES-13 consisted of a circular 3.45 Mb chromosome with a DNA G+C content of 67.0 mol%. Furthering genome mining of strain NJES-13 showed the presence of five biosynthetic gene clusters (BGCs) including one type III PKS responsible for the biosynthesis of the core of gephyromycins, and a series of genes encoding for bacterial EPS biosynthesis. Thus, based on the combined phylogenetic and active metabolites characterization presented in this study, we confidently conclude that strain NJES-13 is a novel, fresh actinobacterial candidate to produce active gephyromycins and microbial bioflocculanting EPS, with potential pharmaceutical, environmental and biotechnological implications. Full article
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11 pages, 2331 KiB  
Article
Screening of Neutrophil Activating Factors from a Metagenome Library of Sponge-Associated Bacteria
by Yoshiko Okamura, Hirokazu Takahashi, Atsuyuki Shiida, Yuto Hirata, Haruko Takeyama and Katsuhiko Suzuki
Mar. Drugs 2021, 19(8), 427; https://doi.org/10.3390/md19080427 - 28 Jul 2021
Cited by 1 | Viewed by 1889
Abstract
Marine sponge-associated bacteria are known as bio-active compound produce. We have constructed metagenome libraries of the bacteria and developed a metagenomic screening approach. Activity-based screening successfully identified novel genes and novel enzymes; however, the efficiency was only in 1 out of 104 [...] Read more.
Marine sponge-associated bacteria are known as bio-active compound produce. We have constructed metagenome libraries of the bacteria and developed a metagenomic screening approach. Activity-based screening successfully identified novel genes and novel enzymes; however, the efficiency was only in 1 out of 104 clones. Therefore, in this study, we thought that bioinformatics could help to reduce screening efforts, and combined activity-based screening with database search. Neutrophils play an important role for the immune system to recognize excreted bacterial by-products as chemotactic factors and are recruited to infection sites to kill pathogens via phagocytosis. These excreted by-products are considered critical triggers that engage the immune system to mount a defense against infection, and identifying these factors may guide developments in medicine and diagnostics. We focused on genes encoding amino acid ligase and peptide synthetase and selected from an in-house sponge metagenome database. Cell-free culture medium of each was used in a neutrophil chemiluminescence assay in luminol reaction. The clone showing maximum activity had a genomic sequence expected to produce a molecule like a phospho-N-acetylmuramyl pentapeptide by the metagenome fragment analysis. Full article
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13 pages, 2028 KiB  
Communication
Full-Length Transcriptome of Thalassiosira weissflogii as a Reference Resource and Mining of Chitin-Related Genes
by Haomiao Cheng, Chris Bowler, Xiaohui Xing, Vincent Bulone, Zhanru Shao and Delin Duan
Mar. Drugs 2021, 19(7), 392; https://doi.org/10.3390/md19070392 - 13 Jul 2021
Cited by 8 | Viewed by 2833
Abstract
β-Chitin produced by diatoms is expected to have significant economic and ecological value due to its structure, which consists of parallel chains of chitin, its properties and the high abundance of diatoms. Nevertheless, few studies have functionally characterised chitin-related genes in diatoms owing [...] Read more.
β-Chitin produced by diatoms is expected to have significant economic and ecological value due to its structure, which consists of parallel chains of chitin, its properties and the high abundance of diatoms. Nevertheless, few studies have functionally characterised chitin-related genes in diatoms owing to the lack of omics-based information. In this study, we first compared the chitin content of three representative Thalassiosira species. Cell wall glycosidic linkage analysis and chitin/chitosan staining assays showed that Thalassiosira weissflogii was an appropriate candidate chitin producer. A full-length (FL) transcriptome of T. weissflogii was obtained via PacBio sequencing. In total, the FL transcriptome comprised 23,362 annotated unigenes, 710 long non-coding RNAs (lncRNAs), 363 transcription factors (TFs), 3113 alternative splicing (AS) events and 3295 simple sequence repeats (SSRs). More specifically, 234 genes related to chitin metabolism were identified and the complete biosynthetic pathways of chitin and chitosan were explored. The information presented here will facilitate T. weissflogii molecular research and the exploitation of β-chitin-derived high-value enzymes and products. Full article
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Review

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35 pages, 4855 KiB  
Review
What Was Old Is New Again: The Pennate Diatom Haslea ostrearia (Gaillon) Simonsen in the Multi-Omic Age
by Noujoud Gabed, Frédéric Verret, Aurélie Peticca, Igor Kryvoruchko, Romain Gastineau, Orlane Bosson, Julie Séveno, Olga Davidovich, Nikolai Davidovich, Andrzej Witkowski, Jon Bent Kristoffersen, Amel Benali, Efstathia Ioannou, Aikaterini Koutsaviti, Vassilios Roussis, Hélène Gâteau, Suliya Phimmaha, Vincent Leignel, Myriam Badawi, Feriel Khiar, Nellie Francezon, Mostefa Fodil, Pamela Pasetto and Jean-Luc Mougetadd Show full author list remove Hide full author list
Mar. Drugs 2022, 20(4), 234; https://doi.org/10.3390/md20040234 - 29 Mar 2022
Cited by 4 | Viewed by 3697
Abstract
The marine pennate diatom Haslea ostrearia has long been known for its characteristic blue pigment marennine, which is responsible for the greening of invertebrate gills, a natural phenomenon of great importance for the oyster industry. For two centuries, this taxon was considered unique; [...] Read more.
The marine pennate diatom Haslea ostrearia has long been known for its characteristic blue pigment marennine, which is responsible for the greening of invertebrate gills, a natural phenomenon of great importance for the oyster industry. For two centuries, this taxon was considered unique; however, the recent description of a new blue Haslea species revealed unsuspected biodiversity. Marennine-like pigments are natural blue dyes that display various biological activities—e.g., antibacterial, antioxidant and antiproliferative—with a great potential for applications in the food, feed, cosmetic and health industries. Regarding fundamental prospects, researchers use model organisms as standards to study cellular and physiological processes in other organisms, and there is a growing and crucial need for more, new and unconventional model organisms to better correspond to the diversity of the tree of life. The present work, thus, advocates for establishing H. ostrearia as a new model organism by presenting its pros and cons—i.e., the interesting aspects of this peculiar diatom (representative of benthic-epiphytic phytoplankton, with original behavior and chemodiversity, controlled sexual reproduction, fundamental and applied-oriented importance, reference genome, and transcriptome will soon be available); it will also present the difficulties encountered before this becomes a reality as it is for other diatom models (the genetics of the species in its infancy, the transformation feasibility to be explored, the routine methods needed to cryopreserve strains of interest). Full article
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