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Marine Drugs
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Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and...
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Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and Their Biotechnological and Pharmaceutical Applications

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

Deadline for manuscript submissions: closed (30 August 2020) | Viewed by 30264

Special Issue Editors

Prof. Dr. Frank Kempken

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Guest Editor
Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University, 24118 Kiel, Germany
Interests: genetics and genomics; marine fungi; marine secondary metabolites; plant mitochondria; fungal eisosomes; fungal auxin pathway
Dr. Abhishek Kumar

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Guest Editor
Department of Genetics and Molecular Biology in Botany, Institute of Botany, Christian-Albrechts-University, 24118 Kiel, Germany
Interests: genetics and genomics; marine fungi; marine secondary metabolites; ocean genomics

Special Issue Information

Dear Colleagues,

Oceans harbor a wide array of living organisms, which produce massive amounts of secondary metabolites. However, these natural products have been neglected in comparisons to similar products from terrestrial organisms. In the last decade, we have noticed progress in the field of characterization of marine secondary metabolites using genetics and genomic methods. These compounds have massive potential in various biotechnological and pharmaceutical applications, such as antibacterial and/or anticancerous roles.

Marine scientists across the globe have been working on the characterization of marine nature compounds with a wide array of technologies; however, it has huge potential for progress in terms of methods, applications, and studies concerning marine natural products.

This Special Issue will be focusing on state-of-the-art methods, potential challenges, and future directions of the characterization of marine natural compounds and their applications as biotechnological and pharmaceutical products. For this proposed Special Issue of Marine Drugs, we invite authors to consider publishing their review articles or original research focusing on topics such as:

  • Bioinformatics and genomic mining tools for characterization of marine secondary metabolite genes and their clusters
  • Marine secondary metabolites characterization using integrative genomics coupling with other methods like RNA-Seq and proteomics
  • Methods and studies for activating silent marine secondary metabolites focusing on abiotic and biotic stresses
  • Development and application of heterologous systems for the expression of biosynthetic gene clusters
  • Advancements of genome editing for characterization of marine secondary metabolites
  • Characterization of new marine natural products using isolation-structure-function based-elucidations
  • Recent developments in biosynthesis of marine natural products

Prof. Dr. Frank Kempken
Dr. Abhishek Kumar
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 origin
  • Secondary metabolite
  • Biosynthetic gene cluster
  • Marine genetics
  • Marine genomics
  • Marine Biotechnology
  • Marine origin
  • Nature products

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Published Papers (5 papers)

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Research

25 pages, 4151 KiB  
Article
Genomics- and Metabolomics-Based Investigation of the Deep-Sea Sediment-Derived Yeast, Rhodotorula mucilaginosa 50-3-19/20B
by Larissa Buedenbender, Abhishek Kumar, Martina Blümel, Frank Kempken and Deniz Tasdemir
Mar. Drugs 2021, 19(1), 14; https://doi.org/10.3390/md19010014 - 30 Dec 2020
Cited by 19 | Viewed by 6970
Abstract
Red yeasts of the genus Rhodotorula are of great interest to the biotechnological industry due to their ability to produce valuable natural products, such as lipids and carotenoids with potential applications as surfactants, food additives, and pharmaceuticals. Herein, we explored the biosynthetic potential [...] Read more.
Red yeasts of the genus Rhodotorula are of great interest to the biotechnological industry due to their ability to produce valuable natural products, such as lipids and carotenoids with potential applications as surfactants, food additives, and pharmaceuticals. Herein, we explored the biosynthetic potential of R. mucilaginosa 50-3-19/20B collected from the Mid-Atlantic Ridge using modern genomics and untargeted metabolomics tools. R. mucilaginosa 50-3-19/20B exhibited anticancer activity when grown on PDA medium, while antimicrobial activity was observed when cultured on WSP-30 medium. Applying the bioactive molecular networking approach, the anticancer activity was linked to glycolipids, namely polyol esters of fatty acid (PEFA) derivatives. We purified four PEFAs (1–4) and the known methyl-2-hydroxy-3-(1H-indol-2-yl)propanoate (5). Their structures were deduced from NMR and HR-MS/MS spectra, but 1–5 showed no anticancer activity in their pure form. Illumina-based genome sequencing, de novo assembly and standard biosynthetic gene cluster (BGC) analyses were used to illustrate key components of the PEFA biosynthetic pathway. The fatty acid producing BGC3 was identified to be capable of producing precursors of PEFAs. Some Rhodotorula strains are able to convert inulin into high-yielding PEFA and cell lipid using a native exo-inulinase enzyme. The genomic locus for an exo-inulinase enzyme (g1629.t1), which plays an instrumental role in the PEFA production via the mannitol biosynthesis pathway, was identified. This is the first untargeted metabolomics study on R. mucilaginosa providing new genomic insights into PEFA biosynthesis. Full article
(This article belongs to the Special Issue Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and Their Biotechnological and Pharmaceutical Applications)
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20 pages, 1308 KiB  
Article
Characterization of the CAZy Repertoire from the Marine-Derived Fungus Stemphylium lucomagnoense in Relation to Saline Conditions
by Wissal Ben Ali, David Navarro, Abhishek Kumar, Elodie Drula, Annick Turbé-Doan, Lydie Oliveira Correia, Stéphanie Baumberger, Emmanuel Bertrand, Craig B. Faulds, Bernard Henrissat, Giuliano Sciara, Tahar Mechichi and Eric Record
Mar. Drugs 2020, 18(9), 461; https://doi.org/10.3390/md18090461 - 9 Sep 2020
Cited by 11 | Viewed by 4109
Abstract
Even if the ocean represents a large part of Earth’s surface, only a few studies describe marine-derived fungi compared to their terrestrial homologues. In this ecosystem, marine-derived fungi have had to adapt to the salinity and to the plant biomass composition. This articles [...] Read more.
Even if the ocean represents a large part of Earth’s surface, only a few studies describe marine-derived fungi compared to their terrestrial homologues. In this ecosystem, marine-derived fungi have had to adapt to the salinity and to the plant biomass composition. This articles studies the growth of five marine isolates and the tuning of lignocellulolytic activities under different conditions, including the salinity. A de novo transcriptome sequencing and assembly were used in combination with a proteomic approach to characterize the Carbohydrate Active Enzymes (CAZy) repertoire of one of these strains. Following these approaches, Stemphylium lucomagnoense was selected for its adapted growth on xylan in saline conditions, its high xylanase activity, and its improved laccase activities in seagrass-containing cultures with salt. De novo transcriptome sequencing and assembly indicated the presence of 51 putative lignocellulolytic enzymes. Its secretome composition was studied in detail when the fungus was grown on either a terrestrial or a marine substrate, under saline and non-saline conditions. Proteomic analysis of the four S. lucomagnoense secretomes revealed a minimal suite of extracellular enzymes for plant biomass degradation and highlighted potential enzyme targets to be further studied for their adaptation to salts and for potential biotechnological applications. Full article
(This article belongs to the Special Issue Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and Their Biotechnological and Pharmaceutical Applications)
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16 pages, 3091 KiB  
Article
Mining Natural Product Biosynthesis in Eukaryotic Algae
by Ellis O’Neill
Mar. Drugs 2020, 18(2), 90; https://doi.org/10.3390/md18020090 - 30 Jan 2020
Cited by 13 | Viewed by 4861
Abstract
Eukaryotic algae are an extremely diverse category of photosynthetic organisms and some species produce highly potent bioactive compounds poisonous to humans or other animals, most notably observed during harmful algal blooms. These natural products include some of the most poisonous small molecules known [...] Read more.
Eukaryotic algae are an extremely diverse category of photosynthetic organisms and some species produce highly potent bioactive compounds poisonous to humans or other animals, most notably observed during harmful algal blooms. These natural products include some of the most poisonous small molecules known and unique cyclic polyethers. However, the diversity and complexity of algal genomes means that sequencing-based research has lagged behind research into more readily sequenced microbes, such as bacteria and fungi. Applying informatics techniques to the algal genomes that are now available reveals new natural product biosynthetic pathways, with different groups of algae containing different types of pathways. There is some evidence for gene clusters and the biosynthetic logic of polyketides enables some prediction of these final products. For other pathways, it is much more challenging to predict the products and there may be many gene clusters that are not identified with the automated tools. These results suggest that there is a great diversity of biosynthetic capacity for natural products encoded in the genomes of algae and suggest areas for future research focus. Full article
(This article belongs to the Special Issue Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and Their Biotechnological and Pharmaceutical Applications)
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12 pages, 4035 KiB  
Article
Functional Characterization and Evolutionary Analysis of Glycine-Betaine Biosynthesis Pathway in Red Seaweed Pyropia yezoensis
by Yunxiang Mao, Nianci Chen, Min Cao, Rui Chen, Xiaowei Guan and Dongmei Wang
Mar. Drugs 2019, 17(1), 70; https://doi.org/10.3390/md17010070 - 21 Jan 2019
Cited by 16 | Viewed by 4661
Abstract
The red seaweed Pyropia yezoensis is an ideal research model for dissecting the molecular mechanisms underlying its robust acclimation to abiotic stresses in intertidal zones. Glycine betaine (GB) was an important osmolyte in maintaining osmotic balance and stabilizing the quaternary structure of complex [...] Read more.
The red seaweed Pyropia yezoensis is an ideal research model for dissecting the molecular mechanisms underlying its robust acclimation to abiotic stresses in intertidal zones. Glycine betaine (GB) was an important osmolyte in maintaining osmotic balance and stabilizing the quaternary structure of complex proteins under abiotic stresses (drought, salinity, etc.) in plants, animals, and bacteria. However, the existence and possible functions of GB in Pyropia remain elusive. In this study, we observed the rapid accumulation of GB in desiccated Pyropia blades, identifying its essential roles in protecting Pyropia cells against severe osmotic stress. Based on the available genomic and transcriptomic information of Pyropia, we computationally identified genes encoding the three key enzymes in the GB biosynthesis pathway: phosphoethanolamine N-methyltransferase (PEAMT), choline dehydrogenase (CDH), and betaine aldehyde dehydrogenase (BADH). Pyropia had an extraordinarily expanded gene copy number of CDH (up to seven) compared to other red algae. Phylogeny analysis revealed that in addition to the one conservative CDH in red algae, the other six might have originated from early gene duplication events. In dehydration stress, multiple CDH paralogs and PEAMT genes were coordinating up-regulated and shunted metabolic flux into GB biosynthesis. An elaborate molecular mechanism might be involved in the transcriptional regulation of these genes. Full article
(This article belongs to the Special Issue Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and Their Biotechnological and Pharmaceutical Applications)
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13 pages, 2132 KiB  
Article
Illustrating and Enhancing the Biosynthesis of Astaxanthin and Docosahexaenoic Acid in Aurantiochytrium sp. SK4
by Jingrun Ye, Mengmeng Liu, Mingxia He, Ying Ye and Junchao Huang
Mar. Drugs 2019, 17(1), 45; https://doi.org/10.3390/md17010045 - 10 Jan 2019
Cited by 46 | Viewed by 9014
Abstract
The marine thraustochytrids are a promising source of docosahexaenoic acid (DHA) and the ketocarotenoid astaxanthin. In this study, the biosynthetic pathways of these two important metabolites in Aurantiochytrium sp. SK4 was illustrated by the analyses of the genome, transcriptome, key enzymes, and pathway [...] Read more.
The marine thraustochytrids are a promising source of docosahexaenoic acid (DHA) and the ketocarotenoid astaxanthin. In this study, the biosynthetic pathways of these two important metabolites in Aurantiochytrium sp. SK4 was illustrated by the analyses of the genome, transcriptome, key enzymes, and pathway products. Two sets of genes were involved in two pathways for the biosynthesis of fatty acids. The absence of Δ-15 desaturase genes and the presence of docosapentaenoic acid (DPA), up to 12% of total fatty acids suggest that Aurantiochytrium sp. SK4 may synthesize DHA mainly via a polyketide synthase (PKS) pathway. Three enzymes, namely geranyl diphosphate synthase (GPPS), farnysyl diphosphate synthase (FPPS), and geranylgeranyle diphosphate synthase (GGPPS) were found to be involved in the formation of GGPP that was subsequently catalyzed to β-carotene by a trifunctional CrtIBY enzyme. β-Carotene might be ketolated and then hydroxylated into astaxanthin based on the carotenoid profiles. The formation of GGPP was proposed to be the limiting steps for carotenoid production. Overexpression of the Archaeoglobus GPS together with the Escherichia coli isopentenyl pyrophosphate isomerase, and Vitreoscilla hemoglobin resulted in not only 1.85- and 5.02-fold increases of total carotenoids and astaxanthin, but also 2.40- and 2.74-fold increases of total fatty acids and DHA. This study provides insights into the biosynthesis of carotenoids and fatty acids in Aurantiochytrium. Full article
(This article belongs to the Special Issue Genetics and Genomics of Marine Secondary Metabolite Gene Clusters and Their Biotechnological and Pharmaceutical Applications)
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