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Bioactive Molecules from Extreme Environments II

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

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 54905

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Dr. Daniela Giordano

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Institute of Biosciences and BioResources (IBBR), Consiglio Nazionale delle Ricerche (CNR), Via Pietro Castellino 111, I-80131 Naples, Italy
Interests: antarctic and arctic marine environments; bacteria; fish; sponges; marine natural products; marine peptides/proteins; protein structure/function; hemoproteins; marine antioxidants; marine anti-UV; functional ingredients; cosmeceuticals; PUFA
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Special Issue Information

Dear Colleagues,

Extreme environments are exposed to harsh conditions of temperature, salinity, osmolarity, UV radiation, pressure, pH, etc., and for this reason, they represent an attractive research area for the discovery of bioactive molecules to be used for biotechnological applications.

In marine ecosystems, extreme environments are important “hot spots” of biodiversity and are expected to harbor organisms that have developed unique strategies to cope with these harsh conditions. Organisms from marine extreme environments are able to biosynthesize novel bioactive compounds, potentially valuable for many applications, including pharmaceuticals, nutraceuticals and cosmeceuticals, for bioremediation, etc.

In consideration of the success of the first Special Issue on “Bioactive Molecules from Extreme Environments”, https://www.mdpi.com/journal/marinedrugs/special_issues/Extreme_Environments, and the relevant interest in the topic, we are pleased to announce the second version of this Special Issue.

In the first Special Issue, 11 Papers were accepted and included, which we now plan to publish as a book. Following the success of the first Special Issue, as Guest Editor, I invite scientists working in this field to contribute to the second edition entitled “Bioactive Molecules from Extreme Environments II”.

I encourage the submission of research papers and reviews focused on bioactive compounds isolated from organisms inhabiting such marine habitats (cold/deep sea, marine hydrothermal vents, and areas of high pressure or high salinity and all other marine environments considered extremes), increasing our knowledge of biological resources in terms of (i) biodiversity, (ii) bioprospecting, and (iii) molecular and enzymatic mechanisms displayed by novel molecules to be used in biotechnological discovery pipelines and pharmaceutical applications.

Dr. Daniela Giordano
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

Marine natural products
Bioactive molecules
Metabolites
Enzymes
Peptides
Extreme environments
Polar regions
Deep sea
Hydrothermal vents

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Related Special Issues

Bioactive Molecules from Extreme Environments in Marine Drugs (12 articles)
Bioactive Molecules from Extreme Environments III in Marine Drugs (6 articles)

Published Papers (13 papers)

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Editorial

Jump to: Research, Review

5 pages, 219 KiB

Open AccessEditorial

Bioactive Molecules from Extreme Environments II

by Daniela Giordano

Mar. Drugs 2021, 19(11), 642; https://doi.org/10.3390/md19110642 - 17 Nov 2021

Cited by 7 | Viewed by 1925

Abstract

Marine organisms are known to produce a wide variety of natural products that are unique in terms of diversity, structural, and functional properties [...] Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

Research

Jump to: Editorial, Review

16 pages, 3915 KiB

Open AccessArticle

A Thermotolerant Marine Bacillus amyloliquefaciens S185 Producing Iturin A5 for Antifungal Activity against Fusarium oxysporum f. sp. cubense

by Pratiksha Singh, Jin Xie, Yanhua Qi, Qijian Qin, Cheng Jin, Bin Wang and Wenxia Fang

Mar. Drugs 2021, 19(9), 516; https://doi.org/10.3390/md19090516 - 11 Sep 2021

Cited by 18 | Viewed by 3481

Abstract

Fusarium wilt of banana (also known as Panama disease), is a severe fungal disease caused by soil-borne Fusarium oxysporum f. sp. cubense (Foc). In recent years, biocontrol strategies using antifungal microorganisms from various niches and their related bioactive compounds have been used to prevent and control Panama disease. Here, a thermotolerant marine strain S185 was identified as Bacillus amyloliquefaciens, displaying strong antifungal activity against Foc. The strain S185 possesses multiple plant growth-promoting (PGP) and biocontrol utility properties, such as producing indole acetic acid (IAA) and ammonia, assimilating various carbon sources, tolerating pH of 4 to 9, temperature of 20 to 50 °C, and salt stress of 1 to 5%. Inoculation of S185 colonized the banana plants effectively and was mainly located in leaf and root tissues. To further investigate the antifungal components, compounds were extracted, fractionated, and purified. One compound, inhibiting Foc with minimum inhibitory concentrations (MICs) of 25 μg/disk, was identified as iturin A5 by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and nuclear magnetic resonance (NMR). The isolated iturin, A5, resulted in severe morphological changes during spore germination and hyphae growth of Foc. These results specify that B. amyloliquefaciens S185 plays a key role in preventing the Foc pathogen by producing the antifungal compound iturin A5, and possesses potential as a cost-effective and sustainable biocontrol strain for Panama disease in the future. This is the first report of isolation of the antifungal compound iturin A5 from thermotolerant marine B. amyloliquefaciens S185. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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15 pages, 1684 KiB

Open AccessArticle

Bioactivity Screening of Antarctic Sponges Reveals Anticancer Activity and Potential Cell Death via Ferroptosis by Mycalols

by Gennaro Riccio, Genoveffa Nuzzo, Gianluca Zazo, Daniela Coppola, Giuseppina Senese, Lucia Romano, Maria Costantini, Nadia Ruocco, Marco Bertolino, Angelo Fontana, Adrianna Ianora, Cinzia Verde, Daniela Giordano and Chiara Lauritano

Mar. Drugs 2021, 19(8), 459; https://doi.org/10.3390/md19080459 - 14 Aug 2021

Cited by 16 | Viewed by 4208

Abstract

Sponges are known to produce a series of compounds with bioactivities useful for human health. This study was conducted on four sponges collected in the framework of the XXXIV Italian National Antarctic Research Program (PNRA) in November-December 2018, i.e., Mycale (Oxymycale) acerata, Haliclona (Rhizoniera) dancoi, Hemimycale topsenti, and Hemigellius pilosus. Sponge extracts were fractioned and tested against hepatocellular carcinoma (HepG2), lung carcinoma (A549), and melanoma cells (A2058), in order to screen for antiproliferative or cytotoxic activity. Two different chemical classes of compounds, belonging to mycalols and suberitenones, were identified in the active fractions. Mycalols were the most active compounds, and their mechanism of action was also investigated at the gene and protein levels in HepG2 cells. Of the differentially expressed genes, ULK1 and GALNT5 were the most down-regulated genes, while MAPK8 was one of the most up-regulated genes. These genes were previously associated with ferroptosis, a programmed cell death triggered by iron-dependent lipid peroxidation, confirmed at the protein level by the down-regulation of GPX4, a key regulator of ferroptosis, and the up-regulation of NCOA4, involved in iron homeostasis. These data suggest, for the first time, that mycalols act by triggering ferroptosis in HepG2 cells. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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22 pages, 16275 KiB

Open AccessArticle

Dermacozine N, the First Natural Linear Pentacyclic Oxazinophenazine with UV–Vis Absorption Maxima in the Near Infrared Region, along with Dermacozines O and P Isolated from the Mariana Trench Sediment Strain Dermacoccus abyssi MT 1.1^T

by Bertalan Juhasz, Dawrin Pech-Puch, Jioji N. Tabudravu, Bastien Cautain, Fernando Reyes, Carlos Jiménez, Kwaku Kyeremeh and Marcel Jaspars

Mar. Drugs 2021, 19(6), 325; https://doi.org/10.3390/md19060325 - 3 Jun 2021

Cited by 6 | Viewed by 4214

Abstract

Three dermacozines, dermacozines N–P (1–3), were isolated from the piezotolerant Actinomycete strain Dermacoccus abyssi MT 1.1^T, which was isolated from a Mariana Trench sediment in 2006. Herein, we report the elucidation of their structures using a combination of 1D/2D NMR, LC-HRESI-MSⁿ, UV–Visible, and IR spectroscopy. Further confirmation of the structures was achieved through the analysis of data from density functional theory (DFT)–UV–Visible spectral calculations and statistical analysis such as two tailed t-test, linear regression-, and multiple linear regression analysis applied to either solely experimental or to experimental and calculated ¹³C-NMR chemical shift data. Dermacozine N (1) bears a novel linear pentacyclic phenoxazine framework that has never been reported as a natural product. Dermacozine O (2) is a constitutional isomer of the known dermacozine F while dermacozine P (3) is 8-benzoyl-6-carbamoylphenazine-1-carboxylic acid. Dermacozine N (1) is unique among phenoxazines due to its near infrared (NIR) absorption maxima, which would make this compound an excellent candidate for research in biosensing chemistry, photodynamic therapy (PDT), opto-electronic applications, and metabolic mapping at the cellular level. Furthermore, dermacozine N (1) possesses weak cytotoxic activity against melanoma (A2058) and hepatocellular carcinoma cells (HepG2) with IC₅₀ values of 51 and 38 μM, respectively. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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13 pages, 1962 KiB

Open AccessArticle

Biogenic Synthesis of Copper Nanoparticles Using Bacterial Strains Isolated from an Antarctic Consortium Associated to a Psychrophilic Marine Ciliate: Characterization and Potential Application as Antimicrobial Agents

by Maria Sindhura John, Joseph Amruthraj Nagoth, Marco Zannotti, Rita Giovannetti, Alessio Mancini, Kesava Priyan Ramasamy, Cristina Miceli and Sandra Pucciarelli

Mar. Drugs 2021, 19(5), 263; https://doi.org/10.3390/md19050263 - 8 May 2021

Cited by 60 | Viewed by 5551

Abstract

In the last decade, metal nanoparticles (NPs) have gained significant interest in the field of biotechnology due to their unique physiochemical properties and potential uses in a wide range of applications. Metal NP synthesis using microorganisms has emerged as an eco-friendly, clean, and viable strategy alternative to chemical and physical approaches. Herein, an original and efficient route for the microbial synthesis of copper NPs using bacterial strains newly isolated from an Antarctic consortium is described. UV-visible spectra of the NPs showed a maximum absorbance in the range of 380–385 nm. Transmission electron microscopy analysis showed that these NPs are all monodispersed, spherical in nature, and well segregated without any agglomeration and with an average size of 30 nm. X-ray powder diffraction showed a polycrystalline nature and face centered cubic lattice and revealed characteristic diffraction peaks indicating the formation of CuONPs. Fourier-transform infrared spectra confirmed the presence of capping proteins on the NP surface that act as stabilizers. All CuONPs manifested antimicrobial activity against various types of Gram-negative; Gram-positive bacteria; and fungi pathogen microorganisms including Escherichia coli, Staphylococcus aureus, and Candida albicans. The cost-effective and eco-friendly biosynthesis of these CuONPs make them particularly attractive in several application from nanotechnology to biomedical science. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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10 pages, 2034 KiB

Open AccessArticle

Svalbamides A and B, Pyrrolidinone-Bearing Lipodipeptides from Arctic Paenibacillus sp.

by Young Eun Du, Eun Seo Bae, Yeonjung Lim, Jang-Cheon Cho, Sang-Jip Nam, Jongheon Shin, Sang Kook Lee, Seung-Il Nam and Dong-Chan Oh

Mar. Drugs 2021, 19(4), 229; https://doi.org/10.3390/md19040229 - 17 Apr 2021

Cited by 7 | Viewed by 3219

Abstract

Two new secondary metabolites, svalbamides A (1) and B (2), were isolated from a culture extract of Paenibacillus sp. SVB7 that was isolated from surface sediment from a core (HH17-1085) taken in the Svalbard archipelago in the Arctic Ocean. The combinational analysis of HR-MS and NMR spectroscopic data revealed the structures of 1 and 2 as being lipopeptides bearing 3-amino-2-pyrrolidinone, d-valine, and 3-hydroxy-8-methyldecanoic acid. The absolute configurations of the amino acid residues in svalbamides A and B were determined using the advanced Marfey’s method, in which the hydrolysates of 1 and 2 were derivatized with l- and d- forms of 1-fluoro-2,4-dinitrophenyl-5-alanine amide (FDAA). The absolute configurations of 1 and 2 were completely assigned by deducing the stereochemistry of 3-hydroxy-8-methyldecanoic acid based on DP4 calculations. Svalbamides A and B induced quinone reductase activity in Hepa1c1c7 murine hepatoma cells, indicating that they represent chemotypes with a potential for functioning as chemopreventive agents. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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12 pages, 2523 KiB

Open AccessArticle

Anti-Food Allergic Compounds from Penicillium griseofulvum MCCC 3A00225, a Deep-Sea-Derived Fungus

by Cui-Ping Xing, Dan Chen, Chun-Lan Xie, Qingmei Liu, Tian-Hua Zhong, Zongze Shao, Guangming Liu, Lian-Zhong Luo and Xian-Wen Yang

Mar. Drugs 2021, 19(4), 224; https://doi.org/10.3390/md19040224 - 16 Apr 2021

Cited by 14 | Viewed by 3012

Abstract

Ten new (1–10) and 26 known (11–36) compounds were isolated from Penicillium griseofulvum MCCC 3A00225, a deep sea-derived fungus. The structures of the new compounds were determined by detailed analysis of the NMR and HRESIMS spectroscopic data. The absolute configurations were established by X-ray crystallography, Marfey’s method, and the ICD method. All isolates were tested for in vitro anti-food allergic bioactivities in immunoglobulin (Ig) E-mediated rat basophilic leukemia (RBL)-2H3 cells. Compound 13 significantly decreased the degranulation release with an IC₅₀ value of 60.3 μM, compared to that of 91.6 μM of the positive control, loratadine. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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15 pages, 3151 KiB

Open AccessArticle

A Crustin from Hydrothermal Vent Shrimp: Antimicrobial Activity and Mechanism

by Yujian Wang, Jian Zhang, Yuanyuan Sun and Li Sun

Mar. Drugs 2021, 19(3), 176; https://doi.org/10.3390/md19030176 - 23 Mar 2021

Cited by 23 | Viewed by 4321

Abstract

Crustin is a type of antimicrobial peptide and plays an important role in the innate immunity of arthropods. We report here the identification and characterization of a crustin (named Crus1) from the shrimp Rimicaris sp. inhabiting the deep-sea hydrothermal vent in Manus Basin (Papua New Guinea). Crus1 shares the highest identity (51.76%) with a Type I crustin of Penaeus vannamei and possesses a whey acidic protein (WAP) domain, which contains eight cysteine residues that form the conserved ‘four-disulfide core’ structure. Recombinant Crus1 (rCrus1) bound to peptidoglycan and lipoteichoic acid, and effectively killed Gram-positive bacteria in a manner that was dependent on pH, temperature, and disulfide linkage. rCrus1 induced membrane leakage and structure damage in the target bacteria, but had no effect on bacterial protoplasts. Serine substitution of each of the 8 Cys residues in the WAP domain did not affect the bacterial binding capacity but completely abolished the bactericidal activity of rCrus1. These results provide new insights into the characteristic and mechanism of the antimicrobial activity of deep sea crustins. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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14 pages, 2115 KiB

Open AccessArticle

The Structure of the Lipid A of Gram-Negative Cold-Adapted Bacteria Isolated from Antarctic Environments

by Flaviana Di Lorenzo, Francesca Crisafi, Violetta La Cono, Michail M. Yakimov, Antonio Molinaro and Alba Silipo

Mar. Drugs 2020, 18(12), 592; https://doi.org/10.3390/md18120592 - 26 Nov 2020

Cited by 12 | Viewed by 2831

Abstract

Gram-negative Antarctic bacteria adopt survival strategies to live and proliferate in an extremely cold environment. Unusual chemical modifications of the lipopolysaccharide (LPS) and the main component of their outer membrane are among the tricks adopted to allow the maintenance of an optimum membrane fluidity even at particularly low temperatures. In particular, the LPS’ glycolipid moiety, the lipid A, typically undergoes several structural modifications comprising desaturation of the acyl chains, reduction in their length and increase in their branching. The investigation of the structure of the lipid A from cold-adapted bacteria is, therefore, crucial to understand the mechanisms underlying the cold adaptation phenomenon. Here we describe the structural elucidation of the highly heterogenous lipid A from three psychrophiles isolated from Terra Nova Bay, Antarctica. All the lipid A structures have been determined by merging data that was attained from the compositional analysis with information from a matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS) and MS² investigation. As lipid A is also involved in a structure-dependent elicitation of innate immune response in mammals, the structural characterization of lipid A from such extremophile bacteria is also of great interest from the perspective of drug synthesis and development inspired by natural sources. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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10 pages, 1255 KiB

Open AccessArticle

Antibacterial Cyclic Tripeptides from Antarctica-Sponge-Derived Fungus Aspergillus insulicola HDN151418

by Chunxiao Sun, Ziping Zhang, Zilin Ren, Liu Yu, Huan Zhou, Yaxin Han, Mudassir Shah, Qian Che, Guojian Zhang, Dehai Li and Tianjiao Zhu

Mar. Drugs 2020, 18(11), 532; https://doi.org/10.3390/md18110532 - 26 Oct 2020

Cited by 30 | Viewed by 3320

Abstract

Three new aspochracin-type cyclic tripeptides, sclerotiotides M–O (1–3), together with three known analogues, sclerotiotide L (4), sclerotiotide F (5), and sclerotiotide B (6), were obtained from the ethyl acetate extract of the fungus Aspergillus insulicola HDN151418, which was isolated from an unidentified Antarctica sponge. Spectroscopic and chemical approaches were used to elucidate their structures. The absolute configuration of the side chain in compound 4 was elucidated for the first time. Compounds 1 and 2 showed broad antimicrobial activity against a panel of pathogenic strains, including Bacillus cereus, Proteus species, Mycobacterium phlei, Bacillus subtilis, Vibrio parahemolyticus, Edwardsiella tarda, MRCNS, and MRSA, with MIC values ranging from 1.56 to 25.0 µM. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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20 pages, 2435 KiB

Open AccessArticle

Effect of Drying Methods on Lutein Content and Recovery by Supercritical Extraction from the Microalga Muriellopsis sp. (MCH35) Cultivated in the Arid North of Chile

by Mari Carmen Ruiz-Domínguez, Paola Marticorena, Claudia Sepúlveda, Francisca Salinas, Pedro Cerezal and Carlos Riquelme

Mar. Drugs 2020, 18(11), 528; https://doi.org/10.3390/md18110528 - 26 Oct 2020

Cited by 15 | Viewed by 2712

Abstract

In this study, we determined the effect of drying on extraction kinetics, yield, and lutein content and recovery of the microalga Muriellopsis sp. (MCH35) using the supercritical fluid extraction (SFE) process. The strain was cultivated in an open-raceways reactor in the presence of seawater culture media and arid outdoor conditions in the north of Chile. Spray-drying (SD) and freeze-drying (FD) techniques were used for dehydrating the microalgal biomass. Extraction experiments were performed by using Box-Behnken designs, and the parameters were studied: pressure (30–50 MPa), temperature (40–70 °C), and co-solvent (0–30% ethanol), with a CO₂ flow rate of 3.62 g/min for 60 min. Spline linear model was applied in the central point of the experimental design to obtain an overall extraction curve and to reveal extraction kinetics involved in the SFE process. A significant increase in all variables was observed when the level of ethanol (15–30% v/v) was increased. However, temperature and pressure were non-significant parameters in the SFE process. The FD method showed an increase in lutein content and recovery by 0.3–2.5-fold more than the SD method. Overall, Muriellopsis sp. (MCH35) is a potential candidate for cost-effective lutein production, especially in desert areas and for different biotechnological applications. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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Review

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123 pages, 12631 KiB

Open AccessReview

Bioactive Compounds from Marine Heterobranchs

by Conxita Avila and Carlos Angulo-Preckler

Mar. Drugs 2020, 18(12), 657; https://doi.org/10.3390/md18120657 - 21 Dec 2020

Cited by 27 | Viewed by 7620

Abstract

The natural products of heterobranch molluscs display a huge variability both in structure and in their bioactivity. Despite the considerable lack of information, it can be observed from the recent literature that this group of animals possesses an astonishing arsenal of molecules from different origins that provide the molluscs with potent chemicals that are ecologically and pharmacologically relevant. In this review, we analyze the bioactivity of more than 450 compounds from ca. 400 species of heterobranch molluscs that are useful for the snails to protect themselves in different ways and/or that may be useful to us because of their pharmacological activities. Their ecological activities include predator avoidance, toxicity, antimicrobials, antifouling, trail-following and alarm pheromones, sunscreens and UV protection, tissue regeneration, and others. The most studied ecological activity is predation avoidance, followed by toxicity. Their pharmacological activities consist of cytotoxicity and antitumoral activity; antibiotic, antiparasitic, antiviral, and anti-inflammatory activity; and activity against neurodegenerative diseases and others. The most studied pharmacological activities are cytotoxicity and anticancer activities, followed by antibiotic activity. Overall, it can be observed that heterobranch molluscs are extremely interesting in regard to the study of marine natural products in terms of both chemical ecology and biotechnology studies, providing many leads for further detailed research in these fields in the near future. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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45 pages, 5401 KiB

Open AccessReview

Marine Terpenoids from Polar Latitudes and Their Potential Applications in Biotechnology

by Laura Núñez-Pons, Andrew Shilling, Cinzia Verde, Bill J. Baker and Daniela Giordano

Mar. Drugs 2020, 18(8), 401; https://doi.org/10.3390/md18080401 - 29 Jul 2020

Cited by 33 | Viewed by 7103

Abstract

Polar marine biota have adapted to thrive under one of the ocean’s most inhospitable scenarios, where extremes of temperature, light photoperiod and ice disturbance, along with ecological interactions, have selected species with a unique suite of secondary metabolites. Organisms of Arctic and Antarctic oceans are prolific sources of natural products, exhibiting wide structural diversity and remarkable bioactivities for human applications. Chemical skeletons belonging to terpene families are the most commonly found compounds, whereas cytotoxic antimicrobial properties, the capacity to prevent infections, are the most widely reported activities from these environments. This review firstly summarizes the regulations on access and benefit sharing requirements for research in polar environments. Then it provides an overview of the natural product arsenal from Antarctic and Arctic marine organisms that displays promising uses for fighting human disease. Microbes, such as bacteria and fungi, and macroorganisms, such as sponges, macroalgae, ascidians, corals, bryozoans, echinoderms and mollusks, are the main focus of this review. The biological origin, the structure of terpenes and terpenoids, derivatives and their biotechnological potential are described. This survey aims to highlight the chemical diversity of marine polar life and the versatility of this group of biomolecules, in an effort to encourage further research in drug discovery. Full article

(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments II)

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