Predicting Antifouling Activity and Acetylcholinesterase Inhibition of Marine-Derived Compounds Using a Computer-Aided Drug Design Approach

UIDB/50006/2020 Norma transit?ria DL 57/2016 UIDP/04378/2020 LA/P/0140/2020Biofouling is the undesirable growth of micro-and macro-organisms on artificial waterimmersed surfaces, which results in high costs for the prevention and maintenance of this process (billion €/year) for aquaculture, shipping and other industries that rely on coastal and off-shore infrastructure. To date, there are still no sustainable, economical and environmentally safe solutions to overcome this challenging phenomenon. A computer-aided drug design (CADD) approach comprising ligand-and structure-based methods was explored for predicting the antifouling activities of marine natural products (MNPs). In the CADD ligand-based method, 141 organic molecules extracted from the ChEMBL database and literature with antifouling screening data were used to build the quantitative structure–activity relationship (QSAR) classification model. An overall predictive accuracy score of up to 71% was achieved with the best QSAR model for external and internal validation using test and training sets. A virtual screening campaign of 14,492 MNPs from Encinar’s website and 14 MNPs that are currently in the clinical pipeline was also carried out using the best QSAR model developed. In the CADD structure-based approach, the 125 MNPs that were selected by the QSAR approach were used in molecular docking experiments against the acetylcholinesterase enzyme. Overall, 16 MNPs were proposed as the most promising marine drug-like leads as antifouling agents, e.g., macrocyclic lactam, macrocyclic alkaloids, indole and pyridine derivatives.publishersversionpublishe

Biodegradation of Plastics and Formation of PHA Bioplastics—A Circular Bioeconomy Approach

This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, IP, in the scope of the project UIDP/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB, and UID/CTM/50025/2020-2023 of the Research Unit on Materials Science—CENIMAT–I3N. FCT/MCTES through project grants PTDC/QUIQUI/119116/2010, PTDC/GEO-FIQ/5162/2014, , and PTDC/EEI-EEE/0415/2021.Plastics are present in the majority of daily-use products worldwide. Due to society’s production and consumption patterns, plastics are accumulating in the environment, causing global pollution issues and intergenerational impacts. Our work aims to contribute to the development of solutions and sustainable methods to mitigate this pressing problem, focusing on the ability of marine-derived actinomycetes to accelerate plastics biodegradation and produce polyhydroxyalkanoates (PHAs), which are biodegradable bioplastics. The thin plastic films’ biodegradation was monitored by weight loss, changes in the surface chemical structure (Infra-Red spectroscopy FTIR-ATR), and by mechanical properties (tensile strength tests). Thirty-six marine-derived actinomycete strains were screened for their plastic biodegradability potential. Among these, Streptomyces gougerotti, Micromonospora matsumotoense, and Nocardiopsis prasina revealed ability to degrade plastic films—low-density polyethylene (LDPE), polystyrene (PS) and polylactic acid (PLA) in varying conditions, namely upon the addition of yeast extract to the culture media and the use of UV pre-treated thin plastic films. Enhanced biodegradation by these bacteria was observed in both cases. S. gougerotti degraded 0.56% of LDPE films treated with UV radiation and 0.67% of PS films when inoculated with yeast extract. Additionally, N. prasina degraded 1.27% of PLA films when these were treated with UV radiation, and yeast extract was added to the culture medium. The main and most frequent differences observed in FTIR-ATR spectra during biodegradation occurred at 1740 cm−1, indicating the formation of carbonyl groups and an increase in the intensity of the bands, which indicates oxidation. Young Modulus decreased by 30% on average. In addition, S. gougerotti and M. matsumotoense, besides biodegrading conventional plastics (LDPE and PS), were also able to use these as a carbon source to produce degradable PHA bioplastics in a circular economy conceptpublishersversionpublishe

Hydrophobic DES Based on Menthol and Natural Organic Acids for Use in Antifouling Marine Coatings

Publisher Copyright: © 2023 The Authors. Published by American Chemical Society.Marine biofouling negatively impacts industries with off-shore infrastructures, such as naval, oil, and aquaculture. To date, there are no ideal sustainable, economic, and environmentally benign solutions to deal with this phenomenon. The advances achieved in green solvents, as well as its application in different industries, such as pharmaceutical and biotechnology, have promoted the emergence of deep eutectic systems (DES). These eutectic systems have applications in various fields and can be revolutionary in the marine-based industrial sector. In this study, the main objective was to investigate the potential use of hydrophobic DES (HDES) based on menthol and natural organic acids for their use as marine antifouling coatings. Our strategy encompassed the physicochemical characterization of different formulations, which allowed us to identify the most appropriate molar ratio and intermolecular interactions for HDES formations. The miscibility of the resulting HDES with the marine coating has been evaluated and proven to be successful. The Men/OL (1:1) system proved to be the most promising in terms of cost-production and thus was the one used in subsequent antifouling tests. The cytotoxicity of this HDES was evaluated using an in vitro cell model (HaCat cells) showing no significant toxicity. Furthermore, the application of this system incorporated into coatings that are used in marine structures was also studied using marine species (Mytilus edulis mussels and Patella vulgata limpets) to evaluate both their antifouling and ecotoxicity effects. HDES Men/OL (1:1) incorporated in marine coatings was promising in reducing marine macrofouling and also proved to be effective at the level of microfouling without viability impairment of the tested marine species. It was revealed to be more efficient than using copper oxide, metallic copper, or ivermectin as antifouling agents. Biochemical assays performed on marine species showed that this HDES does not induce oxidative stress in the tested species. These results are a strong indication of the potential of this HDES to be sustainable and efficiently used in marine fouling control technologies.publishersversionpublishe

Metabolomic Fingerprinting of Salinispora From Atlantic Oceanic Islands

Salinispora (Micromonosporaceae) is an obligate marine bacterium genus consisting of three species that share over 99% 16S rRNA identity. The genome and biosynthetic pathways of the members of this genus have been widely investigated due to their production of species-specific metabolites. However, despite the species’ high genetic similarity, site-specific secondary metabolic gene clusters have been found in Salinispora strains collected at different locations. Therefore, exploring the metabolic expression of Salinispora recovered from different sites may furnish insights into their environmental adaptation or their chemical communication and, further, may lead to the discovery of new natural products. We describe the first occurrence of Salinispora strains in sediments from the Saint Peter and Saint Paul Archipelago (a collection of islets in Brazil) in the Atlantic Ocean, and we investigate the metabolic profiles of these strains by employing mass-spectrometry-based metabolomic approaches, including molecular networking from the Global Natural Products Social Molecular Networking platform. Furthermore, we analyze data from Salinispora strains recovered from sediments from the Madeira Archipelago (Portugal, Macaronesia) in order to provide a wider metabolomic investigation of Salinispora strains from the Atlantic Oceanic islands. Overall, our study evidences a broader geographic influence on the secondary metabolism of Salinispora than was previously proposed. Still, some biosynthetic gene clusters, such as those corresponding to typical chemical signatures of S. arenicola, like saliniketals and rifamycins, are highly conserved among the assessed strains

A new tool for faster construction of marine biotechnology collaborative networks.

The increasing and rapid development in technologies, infrastructures, computational power, data availability and information flow has enabled rapid scientific advances. These entail transdisciplinary collaborations that maximize sharing of data and knowledge and, consequently, results, and possible technology transfer. However, in emerging scientific fields it is sometimes difficult to provide all necessary expertise within existing collaborative circles. This is especially true for marine biotechnology that directly addresses global societal challenges. This article describes the creation of a platform dedicated to facilitating the formation of short or mid-term collaborative networks in marine biotechnology. This online platform (https://www.ocean4biotech.eu/map/) enables experts (researchers and members of the marine biotechnology community in general) to have the possibility to showcase their expertise with the aim of being integrated into new collaborations/consortia on the one hand, or to use it as a search tool to complement the expertise in planned/running collaborations, on the other. The platform was created within the Ocean4Biotech (European transdisciplinary networking platform for marine biotechnology) Action, funded under the framework of the European Cooperation in Science and Technology (COST). To build the platform, an inquiry was developed to identify experts in marine biotechnology and its adjunct fields, to define their expertise, to highlight their infrastructures and facilities and to pinpoint the main bottlenecks in this field. The inquiry was open to all experts in the broad field of marine biotechnology, including non-members of the consortium. The inquiry (https://ee.kobotoolbox.org/single/UKVsBNtD) remains open for insertion of additional expertise and the resulting interactive map can be used as a display and search tool for establishing new collaborations

Comparative Chemical Profiling and Antimicrobial/Anticancer Evaluation of Extracts from Farmed versus Wild Agelas oroides and Sarcotragus foetidus Sponges

This study was implemented in the framework of the research project SPINAQUA (Grant No 239) funded by the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Technology (GSRT) under the “1st call for H.F.R.I. Research Projects for the support of Post-doctoral Researchers”. This publication is based upon work from COST Action CA18238 (Ocean4Biotech), supported by COST (European Cooperation in Science and Technology) program, which provided Short Term Scientific Mission (STSM) grant support to D.V.-M. to perform the experimental work at NOVA-FCT. C.M.P.R. is financially supported by La Caixa Foundation (Grant No LCF/PR/HR21/52410028). Publisher Copyright: © 2023 by the authors.Marine sponges are highly efficient in removing organic pollutants and their cultivation, adjacent to fish farms, is increasingly considered as a strategy for improving seawater quality. Moreover, these invertebrates produce a plethora of bioactive metabolites, which could translate into an extra profit for the aquaculture sector. Here, we investigated the chemical profile and bioactivity of two Mediterranean species (i.e., Agelas oroides and Sarcotragus foetidus) and we assessed whether cultivated sponges differed substantially from their wild counterparts. Metabolomic analysis of crude sponge extracts revealed species-specific chemical patterns, with A. oroides and S. foetidus dominated by alkaloids and lipids, respectively. More importantly, farmed and wild explants of each species demonstrated similar chemical fingerprints, with the majority of the metabolites showing modest differences on a sponge mass-normalized basis. Furthermore, farmed sponge extracts presented similar or slightly lower antibacterial activity against methicillin-resistant Staphylococcus aureus, compared to the extracts resulting from wild sponges. Anticancer assays against human colorectal carcinoma cells (HCT-116) revealed marginally active extracts from both wild and farmed S. foetidus populations. Our study highlights that, besides mitigating organic pollution in fish aquaculture, sponge farming can serve as a valuable resource of biomolecules, with promising potential in pharmaceutical and biomedical applications.publishersversionpublishe

Marine anticancer agents: An overview with a particular focus on their chemical classes

UID/Multi/04378/2019 IF/00700/2014 grant number 216Z167 grant RTA 2015-00010-C03-02 No. PBA/MB/16/01 PDOC/19/02/01The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use.publishersversionpublishe

From the sea to aquafeed: A perspective overview

Aquaculture has been one of the fastest-growing food production systems sectors for over three decades. With its growth, the demand for alternative, cheaper and high-quality feed ingredients is also increasing. Innovation investments on providing new functional feed alternatives have yielded several viable alternative raw materials. Considering all the current feed ingredients, their circular adaption in the aquafeed manufacturing industry is clearly of the utmost importance to achieve sustainable aquaculture in the near future. The use of terrestrial plant materials and animal by-products predominantly used in aquafeed ingredients puts a heavily reliance on terrestrial agroecosystems, which also has its own sustainability concerns. Therefore, the aquafeed industry needs to progress with functional and sustainable alternative raw materials for feed that must be more resilient and consistent, considering a circular perspective. In this review, we assess the current trends in using various marine organisms, ranging from microorganisms (including fungi, thraustochytrids, microalgae and bacteria) to macroalgae and macroinvertebrates as viable biological feed resources. This review focuses on the trend of circular use of resources and the development of new value chains. In this, we present a perspective of promoting novel circular economy value chains that promote the re-use of biological resources as valuable feed ingredients. Thus, we highlight some potentially important marine-derived resources that deserve further investigations for improving or addressing circular aquaculture

Marine Drug Discovery through Computer-Aided Approaches

Besides the importance of our oceans as oxygen factories, food providers, shipping pathways, and tourism enablers, oceans hide an unprecedented wealth of opportunities [...

A computer-driven approach to discover natural product leads for methicillin-resistant staphylococcus aureus infection therapy †

Financial support from Fundacao para a Ciencia e Tecnologia (FCT) Portugal, under Project PTDC/QUIQUI/119116/2010 and grants SFRH/BPD/108237/2015 (F.P.) and IF/00700/2014 (S.P.G.) are greatly appreciated. This work was supported by the LAQV, which is financed by national funds from FCT/MEC (UID/QUI/50006/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007265). This work was also supported by the UCIBIO, which is financed by national funds from FCT/MEC (UID/Multi/04378/2013) and co-financed by the ERDF under the PT2020 Partnership Agreement (POCI-010145-FEDER-007728). The NMR spectrometers are part of The National NMR Facility, supported by FCT (RECI/BBB-BQB/0230/2012).The risk of methicillin-resistant Staphylococcus aureus (MRSA) infection is increasing in both the developed and developing countries. New approaches to overcome this problem are in need. A ligand-based strategy to discover new inhibiting agents against MRSA infection was built through exploration of machine learning techniques. This strategy is based in two quantitative structure–activity relationship (QSAR) studies, one using molecular descriptors (approach A) and the other using descriptors (approach B). In the approach A, regression models were developed using a total of 6645 molecules that were extracted from the ChEMBL, PubChem and ZINC databases, and recent literature. The performance of the regression models was successfully evaluated by internal and external validation, the best model achieved R 2 of 0.68 and RMSE of 0.59 for the test set. In general natural product (NP) drug discovery is a time-consuming process and several strategies for dereplication have been developed to overcome this inherent limitation. In the approach B, we developed a new NP drug discovery methodology that consists in frontloading samples with 1D NMR descriptors to predict compounds with antibacterial activity prior to bioactivity screening for NPs discovery. The NMR QSAR classification models were built using 1D NMR data ( 1 H and 13 C) as descriptors, from crude extracts, fractions and pure compounds obtained from actinobacteria isolated from marine sediments collected off the Madeira Archipelago. The overall predictability accuracies of the best model exceeded 77% for both training and test sets.publishersversionpublishe