From 2012 to 2016 a special issue was edited in the journal Marine Drugs dedicated to marine glycoconjugates with the idea that from the end of the decade 1980-1990 increasing advances of analytical techniques boosted the field of glycobiology contributing to its growth with better recognition of structures and roles of complex molecules such as saccharides, glycoproteins, glycan, glycolipids, and proteoglycans (all defined as glycoconjugates). Tremendous impact in biomedical and biotechnological applications of glycoconjugates, like in terrestrial counterparts and the addition of more significance to the current –omic revolution toward a possible marine glycocode, generally based the hope of these studies.
1. State of the Art
It is commonly accepted that in marine research studies on glycoconjugates have had just selective flourishing in a small number of classical processes (reproduction, chemical communications, bioadhesion). However in the decade 1980-1990 increasing advances of analytical techniques boosted the field of glycobiology contributing to its growth with better recognition of structures and roles of complex molecules such as saccharides, glycoproteins, glycan, glycolipids, and proteoglycans (all defined as glycoconjugates).
Firstly two general points have to be remarked (i) the great molecular diversity, with fucose-containing molecular structures being the most prominent and important for biological activities and (ii) some important glycobiology related processes reviewed or discussed in this special issue. As for the first, the glycosides from marine sponge are reviewed in a very complete literature data analysis. Monosaccharides characterizing these glycosides from marine sponges are more than two dozens types present in mono or oligoforms, free or more often as acylated derivatives. Thought to be membrane constituents, they have important biological activities connected with the biological role as defensive molecules. A quick search in Pubmed for articles dealing with these molecules shows that more than one hundred articles have been published since 2012, demonstrating the ongoing importance of these molecules.
However, the most prominent molecular types present are polysaccharides in nature possessing an important biological activity. Due to the complexity of molecular composition and variability of algae sulfated polysaccharides a first interesting article related to methodology is present in the collection. The article was focused on the development of a simple microplate assay for screening the quality of these molecules. The same topic was later developed by this research group among other interests.
In a general analysis, the structure-activity relationships of algae polysaccharides were investigated using 33 different types prepared for this work investigating their action as anti-complement drug. Influence of molecular weights, the presence of sulfate, branching, and type of monosaccharides present were all aspects analyzed.
In another article the interesting molecule apigalacturonan, that is a kind of apiose-rich pectin occurring in a small number of aquatic monocots was the subject of investigation. After acidic or enzymatic depolymerization the authors reported about structures and anti-tumour activity of different fragments. No further articles were found on this polysaccharide from the publication of this article.
Hyaluronic acid is another important molecule from an economical point of view. As for this polysaccharide, known marine sources are poor in yields and it is currently massively produced by microbial synthesis. The article published explored the production by Streptococcus equi subsp. zooepidemicus in complex media constituted by peptones from Scyliorhinus canicula viscera by-products. The protein constituents from this fishing discards proved to be an appropriate alternative to replace commercial tryptone. The marine by-products valorization is a great topic in marine biotechnology and the same research group later investigated also the use of other economic alternatives from food industry.
Another important review present in this special issue is the one introducing the concept of glycomic with proposed subdivisions that are judged important in marine field. The focus is specially devoted to sulfated fucans and galactans with their respective fucanomics and galactonomics and to the importance of international recognition of these subclassifications within marine glycomics. Indeed different other original articles are present that are focused on these concepts: (i) the evaluation of the anti-tumor activities of the oral administration of fucoidan extracted from the edible seaweed Cladosiphon okamuranus using a tumor (colon 26)-bearing mouse model, (ii) the antiproliferative activity of a nanogel constituted using the algal heterofucan from Spatoglossum schroederi, (iii) the preparation and evaluation of structure-activity relationship of the O-acylated derivative of fucosylated chondroitin sulfate from sea cucumber using the material with a low molecular weight fragment obtained from glycosaminoglycan of the Thelenota ananas, (iv) the purification and characterization of a fucoidanase from a marine bacterium Sphingomonas paucimobilis, a study in the frame of a the search for enzyme activities that efficiently degrade marine polysaccharides for structural analysis and for production of lower-molecular-weight bioactive oligosaccharides.
Another important contribution of the issue, in view of molecular diversity in this field, is the one reporting on the structure of an amino acid-decorated exopolysaccharide originated from a Vibrio alginolyticus strain. The importance of the study resides both on the technical advantages of microbial production that can be easily controlled and is independent of seasonal variations, and on the possible use of these compounds in cosmetics.
Conopeptides constitutes conotoxins and are small peptides present in the venom of cone snails. These compounds contain a high frequency and variability of post-translational modifications such as O-glycosylation of high importance for biological activity. They can be used as specific neuropharmacological agents and chemical probes. A review on the currently existing knowledge of O-glycosylation of conotoxins is present.
Molecular diversity dedicated studies terminated with three additional articles focused on (i) three new ganglioside molecular species isolated from pyloric caeca of the starfish Protoreaster nodosus reporting the first case of invertebrate GM4-type ganglioside having a wide significance from chemical, biological, and biosynthetic points of view and (ii) a structure‐activity relationship study of the carbohydrate moiety of the ganglioside LLG‐3 isolated from the starfish Linchia laevigata  and (iii) the structural investigation of the oligosaccharide portion of the lipooligosaccharide of psychrophilic organism Psychrobacter arcticus  which is important in the frame of studies related to the increase in the number of characterized LPS structures from psychrophiles to find a possible specific connection between the polysaccharide portion and membrane cold adaptation mechanism alternative to the higher content of unsaturated, polyunsaturated, and methyl-branched fatty acids.
Besides molecular diversity as the main subject of the published articles, few were devoted to bioprocesses and molecular mechanisms inherent to marine glycobiology. Namely, a general view of the state of art in the glycobiology of reproductive processes in marine animals where authors focused on what known in the glycobiology from gametogenesis to fertilization and embryo development in marine animals picking up the concept of the species-specific chemical diversity of molecules involved. An interesting article investigating the skin mucus of eel for the induction of apoptosis and antitumor activity on human cells is present in the special issue showing for the first time that eel skin mucus has anti-tumour activity in human cells. The microbial extracellular matrix contains exopolymeric substances (EPS) and proteins; the structural details of the first are not known but are of great importance in processes investigated in a marine isolated strain of Bacillus pumilus . The last article present is focused on lectins that are glycan-binding proteins, namely on MytiLec that is an α-Gal-binding lectin isolated in 2012 from the mussel Mytilus galloprovincialis. Using a cell line with high globotriose expression this lectin has been studied for action on lymphoma cells .
Although the listed contributions are not numerous, after this analysis a conclusion can be drawn about the recognition of the importance of structural determination in glycobiology before the complex roles of all involved molecules can be defined. It is again confirmed too that in the marine field these studies are characterized by selective flourishing in a small number of classical processes. A search for marine glycobiology as keywords, conducted at the time of writing in Science Direct database, accounts for few articles but it is important to mention a modern book as an important source of interesting information. Moreover is important to mention also a new special issue in Marine Drugs entitled Marine glycobiology, glycomics and lectins guest-edited by Prof. Yasuhiro Ozeki in 2018.
- Vladimir I. Kalinin; Natalia V. Ivanchina; Vladimir B. Krasokhin; Tatyana N. Makarieva; Valentin A. Stonik; Glycosides from Marine Sponges (Porifera, Demospongiae): Structures, Taxonomical Distribution, Biological Activities and Biological Roles. Marine Drugs 2012, 10, 1671-1710, 10.3390/md10081671.
- Susanne Lühn; Juliane C. Grimm; Susanne Alban; Simple and Rapid Quality Control of Sulfated Glycans by a Fluorescence Sensor Assay—Exemplarily Developed for the Sulfated Polysaccharides from Red Algae Delesseria sanguinea. Marine Drugs 2014, 12, 2205-2227, 10.3390/md12042205.
- Victor U. Weiss; Monika Golesne; Gernot Friedbacher; Susanne Alban; Wladyslaw W. Szymanski; Günter Allmaier; Martina MarchettiDeschmann; Size and molecular weight determination of polysaccharides by means of nano electrospray gas-phase electrophoretic mobility molecular analysis (nES GEMMA). ELECTROPHORESIS 2018, 39, 1142-1150, 10.1002/elps.201700382.
- Weihua Jin; Wenjing Zhang; Hongze Liang; Quanbin Zhang; The Structure-Activity Relationship between Marine Algae Polysaccharides and Anti-Complement Activity. Marine Drugs 2015, 14, 3, 10.3390/md14010003.
- Youjing Lv; Xindi Shan; Xia Zhao; Chao Cai; Xiaoliang Zhao; Yinzhi Lang; He Zhu; Guangli Yu; Extraction, Isolation, Structural Characterization and Anti-Tumor Properties of an Apigalacturonan-Rich Polysaccharide from the Sea Grass Zostera caespitosa Miki. Marine Drugs 2015, 13, 3710-3731, 10.3390/md13063710.
- José A. Vázquez; Lorenzo Pastrana; Carmen Piñeiro; José A. Teixeira; Ricardo I. Pérez-Martín; Isabel R. Amado; Production of Hyaluronic Acid by Streptococcus zooepidemicus on Protein Substrates Obtained from Scyliorhinus canicula Discards. Marine Drugs 2015, 13, 6537-6549, 10.3390/md13106537.
- Isabel R. Amado; José A. Vázquez; Lorenzo Pastrana; José A. Teixeira; Cheese whey: A cost-effective alternative for hyaluronic acid production by Streptococcus zooepidemicus. Food Chemistry 2016, 198, 54-61, 10.1016/j.foodchem.2015.11.062.
- Vitor H. Pomin; Fucanomics and Galactanomics: Marine Distribution, Medicinal Impact, Conceptions, and Challenges. Marine Drugs 2012, 10, 793-811, 10.3390/md10040793.
- Kazuo Azuma; Toshitsugu Ishihara; Hiroyuki Nakamoto; Takao Amaha; Tomohiro Osaki; Takeshi Tsuka; Tomohiro Imagawa; Saburo Minami; Osamu Takashima; Shinsuke Ifuku; et al. Effects of Oral Administration of Fucoidan Extracted from Cladosiphon okamuranus on Tumor Growth and Survival Time in a Tumor-Bearing Mouse Model. Marine Drugs 2012, 10, 2337-2348, 10.3390/md10102337.
- Nednaldo Dantas-Santos; Arthur Anthunes Jacome Vidal; Jailma Almeida-Lima; Francisco Miguel Gama; Dayanne Lopes Gomes; Ruth Medeiros Oliveira; Silvia Santos Pedrosa; Paula Pereira; Hugo Alexandre Oliveira Rocha; Antiproliferative Activity of Fucan Nanogel. Marine Drugs 2012, 10, 2002-2022, 10.3390/md10092002.
- Na Gao; Wu Lian; Mingyi Wu; Shao Liu; Zi Li; Jinhua Zhao; Preparation and Characterization of O-Acylated Fucosylated Chondroitin Sulfate from Sea Cucumber. Marine Drugs 2012, 10, 1647-1661, 10.3390/md10081647.
- Woo Jung Kim; Jae Kweon Park; Doo Jin Choi; Yong Il Park; Joo Woong Park; Purification and Characterization of a Fucoidanase (FNase S) from a Marine Bacterium Sphingomonas paucimobilis PF-1. Marine Drugs 2015, 13, 4398-4417, 10.3390/md13074398.
- Sophie Drouillard; Isabelle Jeacomine; Laurine Buon; Claire Boisset; Anthony Courtois; Bertrand Thollas; Pierre-Yves Morvan; Romuald Vallée; William Helbert; Romuald Vallã©E; et al. Structure of an Amino Acid-Decorated Exopolysaccharide Secreted by a Vibrio alginolyticus Strain. Marine Drugs 2015, 13, 6723-6739, 10.3390/md13116723.
- Gerrit Gerwig; Henry Hocking; Reto Stöcklin; Johannis Kamerling; Rolf Boelens; Glycosylation of Conotoxins. Marine Drugs 2013, 11, 623-642, 10.3390/md11030623.
- Masanori Inagaki; Ke Pan; Chiaki Tanaka; Ryuichi Higuchi; Tomofumi Miyamoto; Isolation and Structure Elucidation of GM4-Type Gangliosides from the Okinawan Starfish Protoreaster nodosus. Marine Drugs 2012, 10, 2467-2480, 10.3390/md10112467.
- Megumi Yamagishi; Ritsuko Hosoda-Yabe; Hideki Tamai; Miku Konishi; Akihiro Imamura; Hideharu Ishida; Tomio Yabe; Hiromune Ando; Makoto Kiso; Structure-Activity Relationship Study of the Neuritogenic Potential of the Glycan of Starfish Ganglioside LLG-3 ‡. Marine Drugs 2015, 13, 7250-7274, 10.3390/md13127062.
- Angela Casillo; Ermenegilda Parrilli; Sannino Filomena; Buko Lindner; Rosa Lanzetta; Michelangelo Parrilli; Maria Luisa Tutino; Maria Michela Corsaro; Structural Investigation of the Oligosaccharide Portion Isolated from the Lipooligosaccharide of the Permafrost Psychrophile Psychrobacter arcticus 273-4. Marine Drugs 2015, 13, 4539-4555, 10.3390/md13074539.
- Alessandra Gallo; Maria Costantini; Glycobiology of Reproductive Processes in Marine Animals: The State of the Art. Marine Drugs 2012, 10, 2861-2892, 10.3390/md10122861.
- Choong-Hwan Kwak; Sook-Hyun Lee; Sung-Kyun Lee; Sun-Hyung Ha; Seok-Jong Suh; Kyung-Min Kwon; Tae-Wook Chung; Ki-Tae Ha; Young-Chae Chang; Young-Choon Lee; et al. Induction of Apoptosis and Antitumor Activity of Eel Skin Mucus, Containing Lactose-Binding Molecules, on Human Leukemic K562 Cells. Marine Drugs 2015, 13, 3936-3949, 10.3390/md13063936.
- Blanda Di Luccia; Antonio Riccio; Adele Vanacore; Loredana Baccigalupi; Antonio Molinaro; Ezio Ricca; Matrix Production, Pigment Synthesis, and Sporulation in a Marine Isolated Strain of Bacillus pumilus. Marine Drugs 2015, 13, 6472-6488, 10.3390/md13106472.
- Imtiaj Hasan; Shigeki Sugawara; Yuki Fujii; Yasuhiro Koide; Daiki Terada; Naoya Iimura; Toshiyuki Fujiwara; Keisuke G. Takahashi; Nobuhiko Kojima; Sultana Rajia; et al. MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt’s Lymphoma Cells to Trigger Apoptosis through Multiple Pathways. Marine Drugs 2015, 13, 7377-7389, 10.3390/md13127071.
- Various. Marine glycobiology: principles and applications; Se-Kwon Kim, Eds.; CRC Press: Boca Raton, 2017; pp. -.