From Seaside to Bedside: Dedicated to Professor José María Fernández Sousa-Faro

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Marine Pharmacology".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 7143

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Research & Development Area, Pharmamar S.A. Pol. Ind. La Mina Norte, Avda. de los Reyes 1, 28770 Colmenar Viejo, Spain
Interests: marine natural products
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Guest Editor
1. School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa
2. Department of Organic Chemistry, University of Barcelona, Barcelona, Spain
Interests: antimicrobial peptides; solid-phase chemistry; combinatorial chemistry; drug delivery systems; peptide drug conjugates; orthogonal chemistry; drug discovery; biomaterials
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Special Issue Information

Dear Colleagues,

Professor José María Fernández Sousa-Faro has a degree in Chemistry (1967) and a doctorate in Biochemistry (1971) from Universidad Complutense, Madrid. Between 1971 and 1979, he was a tenured professor and subsequently held the position of Chair of Biochemistry at the University of Santiago de Compostela. He received an Honorary Doctorate from Universidad Antonio de Nebrija (Madrid) and was awarded Spain’s National Biotechnology Prize, both in 2009.

Between 1967 and 1979, he worked at the following institutions: Institut für Physikalische Chemie at the University of Basel (Switzerland), Department of Molecular Biology at Washington University in Saint Louis, Missouri (USA),  L’Institut de Biologie Physico-Chimique at Fondation Edmond de Rothschild in Paris (France), and the research laboratories of ICI Pharmaceuticals Division, Alderley Edge, and Shell in Sittingbourne (UK).

He has over 100 academic publications and patents in the fields of biochemistry, molecular biology, and anti-infective and anti-tumor drugs, and a worldwide reputation.

Between 1979 and 1985, Professor Fernández Sousa-Faro was Research Director at Antibióticos S.A.

In 1986, Professor Fernández Sousa-Faro founded PharmaMar S.A. in Spain, as a unique pioneering company with an international presence, inspired by marine exploration to discover novel medicines, first for oncology and more recently for fighting viral infections. 

PharmaMar S.A. was the first company in the world to market a marine-derived anticancer drug and has successfully brought three marine-derived drugs to the oncology market, Yondelis® (trabectedin), Zepzelca® (lurbinectedin), and Aplidin® (plitidepsin), with several more in clinical development as part of its discovery pipeline.

Professor Fernández Sousa-Faro has been, and continues to be, a visionary about the impact of science in society; “The sea is the inspiration, the science is the motor, and the patients are the motivation”.

Professor Fernández Sousa-Faro has successfully pioneered multiple successful private–public partnerships and created a network of hundreds of collaborators across the five continents.

In this Special Issue of Marine Drugs, his scientific collaborators, but also friends, want to pay tribute to the scientist, the entrepreneur, and the remarkable man, Professor José María Fernández Sousa-Faro.

Dr. Carmen Cuevas
Prof. Dr. Fernando Albericio
Guest Editors

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Keywords

  • marine natural products
  • marine pharmacology
  • marine-derived drugs
  • anti-infective drugs
  • anti-tumor drugs

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Published Papers (3 papers)

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Research

20 pages, 4189 KiB  
Article
Regulation of Safracin Biosynthesis and Transport in Pseudomonas poae PMA22
by J. Gerardo Hernández Delgado, Miguel G. Acedos, Fernando de la Calle, Pilar Rodríguez, José Luis García and Beatriz Galán
Mar. Drugs 2024, 22(9), 418; https://doi.org/10.3390/md22090418 - 13 Sep 2024
Viewed by 1281
Abstract
Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins’ biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by Pa [...] Read more.
Pseudomonas poae PMA22 produces safracins, a family of compounds with potent broad-spectrum anti-bacterial and anti-tumor activities. The safracins’ biosynthetic gene cluster (BGC sac) consists of 11 ORFs organized in two divergent operons (sacABCDEFGHK and sacIJ) that are controlled by Pa and Pi promoters. Contiguous to the BGC sac, we have located a gene that encodes a putative global regulator of the LysR family annotated as MexT that was originally described as a transcriptional activator of the MexEF-OprN multidrug efflux pump in Pseudomonas. Through both in vitro and in vivo experiments, we have demonstrated the involvement of the dual regulatory system MexT-MexS on the BGC sac expression acting as an activator and a repressor, respectively. The MexEF-OprN transport system of PMA22, also controlled by MexT, was shown to play a fundamental role in the metabolism of safracin. The overexpression of mexEF-oprN in PMA22 resulted in fourfold higher production levels of safracin. These results illustrate how a pleiotropic regulatory system can be critical to optimizing the production of tailored secondary metabolites, not only through direct interaction with the BGC promoters, but also by controlling their transport. Full article
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11 pages, 1357 KiB  
Article
From Sea Sponge to Clinical Trials: Starting the Journey of the Novel Compound PM742
by Patricia G. Cruz, Rogelio Fernández, Raquel Rodríguez-Acebes, Marta Martínez-Díez, Gema Santamaría-Núñez, Marta Pérez and Carmen Cuevas
Mar. Drugs 2024, 22(8), 339; https://doi.org/10.3390/md22080339 - 26 Jul 2024
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Abstract
PM742 (1), a new chemical entity, has been isolated from the sponge Discodermia du Bocage collected in the Pacific Ocean. This compound showed strong in vitro cytotoxicity against several human tumor cell lines as well as a tubulin depolymerization mechanism of [...] Read more.
PM742 (1), a new chemical entity, has been isolated from the sponge Discodermia du Bocage collected in the Pacific Ocean. This compound showed strong in vitro cytotoxicity against several human tumor cell lines as well as a tubulin depolymerization mechanism of action, which led us to conduct an extensive Structure-Activity-Relationship study through the synthesis of different analogs. As a result, a derivatively named PM534 (2) is currently in its first human Phase I clinical trial. Herein, we present a comprehensive review of the isolation, structural elucidation, and antitumor activities of the parent compound PM742. Full article
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13 pages, 1539 KiB  
Article
Cellulamides: A New Family of Marine-Sourced Linear Peptides from the Underexplored Cellulosimicrobium Genus
by Mariana Girão, José Murillo-Alba, Jesús Martín, Ignacio Pérez-Victoria, Ricardo B. Leite, Ralph Urbatzka, Pedro N. Leão, Maria F. Carvalho and Fernando Reyes
Mar. Drugs 2024, 22(6), 268; https://doi.org/10.3390/md22060268 - 11 Jun 2024
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Abstract
Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained [...] Read more.
Bioprospecting the secondary metabolism of underexplored Actinomycetota taxa is a prolific route to uncover novel chemistry. In this work, we report the isolation, structure elucidation, and bioactivity screening of cellulamides A and B (1 and 2), two novel linear peptides obtained from the culture of the macroalga-associated Cellulosimicrobium funkei CT-R177. The host of this microorganism, the Chlorophyta Codium tomentosum, was collected in the northern Portuguese coast and, in the scope of a bioprospecting study focused on its associated actinobacterial community, strain CT-R177 was isolated, taxonomically identified, and screened for the production of antimicrobial and anticancer compounds. Dereplication of a crude extract of this strain using LC-HRMS(/MS) analysis unveiled a putative novel natural product, cellulamide A (1), that was isolated following mass spectrometry-guided fractionation. An additional analog, cellulamide B (2) was obtained during the chromatographic process and chemically characterized. The chemical structures of the novel linear peptides, including their absolute configurations, were elucidated using a combination of HRMS, 1D/2D NMR spectroscopy, and Marfey’s analysis. Cellulamide A (1) was subjected to a set of bioactivity screenings, but no significant biological activity was observed. The cellulamides represent the first family of natural products reported from the Actinomycetota genus Cellulosimicrobium, showcasing not only the potential of less-explored taxa but also of host-associated marine strains for novel chemistry discovery. Full article
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