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Marine Drugs
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Genome Mining and Synthetic Biology in Marine Natural Products Discovery
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Genome Mining and Synthetic Biology in Marine Natural Products Discovery

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

Deadline for manuscript submissions: closed (30 October 2020) | Viewed by 26340

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editor

Dr. Maria Costantini

E-Mail Website
Guest Editor
Department of Marine Biotechnology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy
Interests: genomic/transcriptomic; marine biotechnology; metabolites in microalgae; nutraceuticals in fish; acquaculture
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,                

Oceans cover nearly 70% of the earth surface and host a huge ecological, chemical and biological diversity.  The natural conditions of the sea favored the production of a great variety of novel molecules with a great pharmaceutical potential in marine organisms, which are unique for their structural and functional features respect to terrestrial ones. Innovation in the field is going hand in hand with the funding of several FP7 and H2020 projects projects under the topic “Blue growth”, with the common final goal to achieve a more environmentally-friendly approach to drug discovery to overcome negative impacts on the environment linked to the over-utilization of marine resources and the use of destructive collection practices.

Driven by the rapidly decreasing cost and increasing throughput of DNA sequencing technologies, significant progress in genomics has renewed interest in natural product discovery. Rapidly expanding genomic and metagenomic datasets reveal a vast number of biosynthetic gene clusters (BGCs) in nature, which are predicted to encode novel biomedically relevant molecules. This ‘top-down’ discovery approach can only provide to access to a small fraction of biosynthetic compounds, given that majority of microorganisms cannot be isolated or cultured. Furthermore, even in culturable organisms, the encoded secondary metabolites of many biosynthetic gene clusters are unknown. This may be due to strong down-regulation of product biosynthesis at the transcriptional, translational and/or post-translational levels in the absence of the right activating cues in the laboratory. Alternatively, secondary metabolites that are produced at very low yields may escape detection and characterization. Natural product discovery, which used to be predominantly an analytical chemistry problem, has become a challenge in genomics and molecular biology on how to manipulate relevant genes and sequences to produce the desired encoded metabolites.

Dr. Maria Costantini
Guest Editor

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

  • Gene clusters
  • Secondary metabolites
  • Metagenomics
  • environmentally-friendly approach

Published Papers (6 papers)

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Editorial

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3 pages, 152 KiB  
Editorial
Genome Mining and Synthetic Biology in Marine Natural Product Discovery
by Maria Costantini
Mar. Drugs 2020, 18(12), 615; https://0-doi-org.brum.beds.ac.uk/10.3390/md18120615 - 03 Dec 2020
Cited by 2 | Viewed by 1672
Abstract
n/a Full article
(This article belongs to the Special Issue Genome Mining and Synthetic Biology in Marine Natural Products Discovery)

Research

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18 pages, 4484 KiB  
Article
Monogalactosyldiacylglycerol and Sulfolipid Synthesis in Microalgae
by Gennaro Riccio, Daniele De Luca and Chiara Lauritano
Mar. Drugs 2020, 18(5), 237; https://0-doi-org.brum.beds.ac.uk/10.3390/md18050237 - 01 May 2020
Cited by 25 | Viewed by 4003
Abstract
Microalgae, due to their huge taxonomic and metabolic diversity, have been shown to be a valuable and eco-friendly source of bioactive natural products. The increasing number of genomic and transcriptomic data will give a great boost for the study of metabolic pathways involved [...] Read more.
Microalgae, due to their huge taxonomic and metabolic diversity, have been shown to be a valuable and eco-friendly source of bioactive natural products. The increasing number of genomic and transcriptomic data will give a great boost for the study of metabolic pathways involved in the synthesis of bioactive compounds. In this study, we analyzed the presence of the enzymes involved in the synthesis of monogalactosyldiacylglycerols (MGDGs) and sulfoquinovosyldiacylglycerols (SQDG). Both compounds have important biological properties. MGDGs present both anti-inflammatory and anti-cancer activities while SQDGs present immunostimulatory activities and inhibit the enzyme glutaminyl cyclase, which is involved in Alzheimer’s disease. The Ocean Global Atlas (OGA) database and the Marine Microbial Eukaryotic Transcriptome Sequencing Project (MMETSP) were used to search MGDG synthase (MGD), UDP-sulfoquinovose synthase (SQD1), and sulfoquinovosyltransferase (SQD2) sequences along microalgal taxa. In silico 3D prediction analyses for the three enzymes were performed by Phyre2 server, while binding site predictions were performed by the COACH server. The analyzed enzymes are distributed across different taxa, which confirms the importance for microalgae of these two pathways for thylakoid physiology. MGD genes have been found across almost all analyzed taxa and can be separated in two different groups, similarly to terrestrial plant MGD. SQD1 and SQD2 genes are widely distributed along the analyzed taxa in a similar way to MGD genes with some exceptions. For Pinguiophyceae, Raphidophyceae, and Synurophyceae, only sequences coding for MGDG were found. On the contrary, sequences assigned to Ciliophora and Eustigmatophyceae were exclusively corresponding to SQD1 and SQD2. This study reports, for the first time, the presence/absence of these enzymes in available microalgal transcriptomes, which gives new insights on microalgal physiology and possible biotechnological applications for the production of bioactive lipids. Full article
(This article belongs to the Special Issue Genome Mining and Synthetic Biology in Marine Natural Products Discovery)
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18 pages, 3377 KiB  
Article
Genome Sequencing and Analysis of Thraustochytriidae sp. SZU445 Provides Novel Insights into the Polyunsaturated Fatty Acid Biosynthesis Pathway
by Xingyu Zhu, Shuangfei Li, Liangxu Liu, Siting Li, Yanqing Luo, Chuhan Lv, Boyu Wang, Christopher H. K. Cheng, Huapu Chen and Xuewei Yang
Mar. Drugs 2020, 18(2), 118; https://0-doi-org.brum.beds.ac.uk/10.3390/md18020118 - 18 Feb 2020
Cited by 22 | Viewed by 3745
Abstract
Thraustochytriidae sp. have broadly gained attention as a prospective resource for the production of omega-3 fatty acids production in significant quantities. In this study, the whole genome of Thraustochytriidae sp. SZU445, which produces high levels of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), [...] Read more.
Thraustochytriidae sp. have broadly gained attention as a prospective resource for the production of omega-3 fatty acids production in significant quantities. In this study, the whole genome of Thraustochytriidae sp. SZU445, which produces high levels of docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA), was sequenced and subjected to protein annotation. The obtained clean reads (63.55 Mb in total) were assembled into 54 contigs and 25 scaffolds, with maximum and minimum lengths of 400 and 0.0054 Mb, respectively. A total of 3513 genes (24.84%) were identified, which could be classified into six pathways and 44 pathway groups, of which 68 genes (1.93%) were involved in lipid metabolism. In the Gene Ontology database, 22,436 genes were annotated as cellular component (8579 genes, 38.24%), molecular function (5236 genes, 23.34%), and biological process (8621 genes, 38.42%). Four enzymes corresponding to the classic fatty acid synthase (FAS) pathway and three enzymes corresponding to the classic polyketide synthase (PKS) pathway were identified in Thraustochytriidae sp. SZU445. Although PKS pathway-associated dehydratase and isomerase enzymes were not detected in Thraustochytriidae sp. SZU445, a putative DHA- and DPA-specific fatty acid pathway was identified. Full article
(This article belongs to the Special Issue Genome Mining and Synthetic Biology in Marine Natural Products Discovery)
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11 pages, 1591 KiB  
Article
Cloning, Expression, and Characterization of a New PL25 Family Ulvan Lyase from Marine Bacterium Alteromonas sp. A321
by Jian Gao, Chunying Du, Yongzhou Chi, Siqi Zuo, Han Ye and Peng Wang
Mar. Drugs 2019, 17(10), 568; https://0-doi-org.brum.beds.ac.uk/10.3390/md17100568 - 08 Oct 2019
Cited by 24 | Viewed by 2966
Abstract
Ulvan lyases can degrade ulvan to oligosaccharides with potent biological activity. A new ulvan lyase gene, ALT3695, was identified in Alteromonas sp. A321. Soluble expression of ALT3695 was achieved in Escherichia coli BL21 (DE3). The 1314-bp gene encoded a protein with 437 [...] Read more.
Ulvan lyases can degrade ulvan to oligosaccharides with potent biological activity. A new ulvan lyase gene, ALT3695, was identified in Alteromonas sp. A321. Soluble expression of ALT3695 was achieved in Escherichia coli BL21 (DE3). The 1314-bp gene encoded a protein with 437 amino acid residues. The amino acid sequence of ALT3695 exhibited low sequence identity with polysaccharide lyase family 25 (PL25) ulvan lyases from Pseudoalteromonas sp. PLSV (64.14% identity), Alteromonas sp. LOR (62.68% identity), and Nonlabens ulvanivorans PLR (57.37% identity). Recombinant ALT3695 was purified and the apparent molecular weight was about 53 kDa, which is different from that of other polysaccharide-degrading enzymes identified in Alteromonas sp. A321. ALT3695 exhibited maximal activity in 50 mM Tris-HCl buffer at pH 8.0 and 50 °C. ALT3695 was relatively thermostable, as 90% activity was observed after incubation at 40 °C for 3 h. The Km and Vmax values of ALT3695 towards ulvan were 0.43 mg·mL−1 and 0.11 μmol·min−1·mL−1, respectively. ESI-MS analysis showed that enzymatic products were mainly disaccharides and tetrasaccharides. This study reports a new PL25 family ulvan lyase, ALT3695, with properties that suggest its great potential for the preparation of ulvan oligosaccharides. Full article
(This article belongs to the Special Issue Genome Mining and Synthetic Biology in Marine Natural Products Discovery)
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12 pages, 1665 KiB  
Article
Discovery of Two New Sorbicillinoids by Overexpression of the Global Regulator LaeA in a Marine-Derived Fungus Penicillium dipodomyis YJ-11
by Jing Yu, Huan Han, Xianyan Zhang, Chuanteng Ma, Chunxiao Sun, Qian Che, Qianqun Gu, Tianjiao Zhu, Guojian Zhang and Dehai Li
Mar. Drugs 2019, 17(8), 446; https://0-doi-org.brum.beds.ac.uk/10.3390/md17080446 - 28 Jul 2019
Cited by 28 | Viewed by 3551
Abstract
Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) [...] Read more.
Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) and 10,11,16,17-tetrahydrobislongiquinolide (2), as well as four known analogues, bislongiquinolide (3), 16,17-dihydrobislongiquinolide (4), sohirnone A (5), and 2′,3′-dihydrosorbicillin (6). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds. Full article
(This article belongs to the Special Issue Genome Mining and Synthetic Biology in Marine Natural Products Discovery)
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Review

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17 pages, 603 KiB  
Review
Genome Mining as New Challenge in Natural Products Discovery
by Luisa Albarano, Roberta Esposito, Nadia Ruocco and Maria Costantini
Mar. Drugs 2020, 18(4), 199; https://0-doi-org.brum.beds.ac.uk/10.3390/md18040199 - 09 Apr 2020
Cited by 73 | Viewed by 9508
Abstract
Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. [...] Read more.
Drug discovery is based on bioactivity screening of natural sources, traditionally represented by bacteria fungi and plants. Bioactive natural products and their secondary metabolites have represented the main source for new therapeutic agents, used as drug leads for new antibiotics and anticancer agents. After the discovery of the first biosynthetic genes in the last decades, the researchers had in their hands the tool to understand the biosynthetic logic and genetic basis leading to the production of these compounds. Furthermore, in the genomic era, in which the number of available genomes is increasing, genome mining joined to synthetic biology are offering a significant help in drug discovery. In the present review we discuss the importance of genome mining and synthetic biology approaches to identify new natural products, also underlining considering the possible advantages and disadvantages of this technique. Moreover, we debate the associated techniques that can be applied following to genome mining for validation of data. Finally, we review on the literature describing all novel natural drugs isolated from bacteria, fungi, and other living organisms, not only from the marine environment, by a genome-mining approach, focusing on the literature available in the last ten years. Full article
(This article belongs to the Special Issue Genome Mining and Synthetic Biology in Marine Natural Products Discovery)
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