Genome Mining and Drug Discovery of Marine and Halophilic Microorganisms

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Biotechnology Related to Drug Discovery or Production".

Deadline for manuscript submissions: 31 January 2025 | Viewed by 4246

Special Issue Editor


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Guest Editor
Microbiology and Parasitology, University of Sevilla, Sevilla, Spain
Interests: taxonomy; halophilic microorganism; metagenomic; biodiversity
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Special Issue Information

Dear Colleagues,

Marine and halophilic microorganisms, including bacteria, archaea, fungi, phytoplankton, and larger algae, as well as some invertebrates, are currently considered potentially promising sources of bioactive substances. Findings related to new marine and halophilic microorganisms reveal the existence of native strains that produce a variety of chemically and biologically interesting secondary metabolites for the development and production of novel compounds of significance in the pharmaceutical, cosmetic, nutritional supplements, biomolecules, biocatalysts, agrochemicals, chemical industries. Research on new metabolites of marine/halophilic origin has increased considerably in recent years. Of all these secondary metabolites, the application antibiotics and drugs to treat cancer are particularly relevant due to the problems of bacterial resistance that threaten public health and the large number of carcinogenic processes that take place.

On the other hand, recent advances in DNA sequencing have led to an enormous increase in the number of published procaryotes genomes and bioinformatics tools developed to analyze the biosynthetic potential of natural products via various “genome mining” approaches.

The microorganisms that we can cultivate are much fewer than those that actually exist in their natural habitats, including, of course, marine and halophilic environments; therefore, the search for new microorganisms that can be cultivated in these environments is a great challenge, and if we consider that many of these microorganisms are capable of producing secondary metabolites, they constitute a large field to discover.

Antimicrobial resistance is one of the major health problems facing humanity. More and more superbugs capable of overcoming available antibiotics are being detected and, if resistance continues to escalate at the current rate, some 10 million people a year will die from bacterial infections by 2050, at a global economic cost that will exceed USD 100,000 million.

In recent years, in order to face these great public health problems, various marine and halophilic ecosystems have been explored, representing a popular area in the search for new bioactive metabolites. The increasing appearance of antibiotic-resistant pathogens has generated the need to evaluate various natural compounds with antimicrobial activity as an alternative in the treatment of infectious and contagious diseases and, in this way, counteract some of these public and veterinary health problems.

It should also be noted that cancer is a disease that has great relevance today because it is among the most serious health problems worldwide. As such, there is a great need to search for new therapeutic options, where bioactive compounds are presented as a promising alternative. The search for new bioactive compounds in marine and halophilic microorganisms is an alternative that has attracted much interest in recent years.

This Special Issue invites academic and industry scientists to submit reviews and original research articles addressing both the discovery of new marine bacteria that produce novel compounds and genomics-driven studies on marine bacteria that focus on natural product discovery and characterization.

Dr. Cristina Sánchez-Porro
Guest Editor

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Keywords

  • halophilic
  • microorganisms
  • metagenomic
  • genome mining
  • gene clusters
  • biodiversity
  • antibiotics
  • anticancer
  • secondary metabolites
  • bioactive molecules

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Published Papers (3 papers)

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Research

13 pages, 2599 KiB  
Article
Heterologous Expression of Type II PKS Gene Cluster Leads to Diversified Angucyclines in Streptomyces albus J1074
by Xiaoting Zhang, Falei Zhang, Chen Li, Jiayi Li, Xiao Xu, Tianjiao Zhu, Qian Che, Deihai Li and Guojian Zhang
Mar. Drugs 2024, 22(11), 480; https://doi.org/10.3390/md22110480 - 22 Oct 2024
Viewed by 909
Abstract
Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host [...] Read more.
Heterologous expression has emerged as an effective strategy in activating Streptomyces cryptic gene clusters or improving yield. Eight compounds were successfully obtained by heterologous expression of the type II PKS gene cluster spi derived from marine Streptomyces sp. HDN155000 in the chassis host Streptomyces albus J1074. The structures with absolute configurations were elucidated using extensive MS and NMR spectroscopic methods, as well as theoretical NMR calculations and electronic circular dichroism (ECD) calculations. Interestingly, compound WS009 Z (2) contains a rare thiomethyl group, angumycinone T (4) has a novel oxo-bridge formed between C12a and C4, and angumycinone X (3) showed cytotoxicity toward K562 and NCI-H446/EP cell lines. Full article
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18 pages, 10761 KiB  
Article
Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach
by Tan Liu, Xi Gui, Gang Zhang, Lianzhong Luo and Jing Zhao
Mar. Drugs 2024, 22(7), 302; https://doi.org/10.3390/md22070302 - 28 Jun 2024
Viewed by 1539
Abstract
The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic [...] Read more.
The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22—derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications. Full article
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11 pages, 3393 KiB  
Article
Discovery of a Novel Chromone Enantiomer and the Precursors of Nonactic Acid from the Coral-Reef-Derived Streptomyces sp. SCSIO 66814
by Wenping Ding, Yanqun Li, Xingyu Li, Jiajia Yin, Songbiao Shi, Xinpeng Tian, Si Zhang and Hao Yin
Mar. Drugs 2024, 22(4), 181; https://doi.org/10.3390/md22040181 - 17 Apr 2024
Viewed by 1269
Abstract
Three pairs of enantiomers (13)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (57) were [...] Read more.
Three pairs of enantiomers (13)—the new 12R-aloesol (1a) and two new fatty acids (2 and 3)—and one new natural product (4) together three known compounds (57) were isolated from a coral-reef-derived Streptomyces sp. SCSIO 66814. Their structures were determined through extensive spectroscopic analysis, chiral analysis, and single-crystal X-ray diffraction data. Compounds 2 and 3 were presumed to be intermediates for further generating homononactic acid (5) and nonactic acid, and the latter two molecules were able to act as precursors to form macrotetrolides with remarkable biological activity. The isolation of related precursors, compounds 25, provided more evidence to support the proposal of a plausible biosynthetic pathway for nonactic acid and its homologs. Additionally, (+)-1 exhibited a weak activity against DPPH radicals. Full article
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