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Available online at www.sciencedirect.com
Red microalgal cell-wall polysaccharides: biotechnological
aspects
Shoshana (Malis) Arad1 and Oshrat Levy-Ontman2
The area of sugars and glycosylation is not as well developed
as other fields in cell biology owing to biotechnological
constraints. However, the biotechnological potential of sugars,
including polysaccharides, is the driving force pushing
research efforts to meet the challenge. Algae produce cell-wall
sulfated polysaccharides, with those of the red unicells, which
dissolve into the medium, having unique characteristics—
structure, composition, fluid dynamics, and extreme stability.
These characteristics, combined with polysaccharide
bioactivities, offer a vast range of potential applications.
Research has thus been directed toward an in-depth
understanding of the molecular structure, biosynthesis, and
characteristics of the red microalgal sulfated polysaccharides
and to the development of molecular-genetic tools, aiming at
large-scale production for applications that can benefit
humanity.
Addresses
1
Department of Biotechnology Engineering, Ben-Gurion University of
the Negev, Beer-Sheva 84105, Israel
2
Department of Chemical Engineering, Sami Shamoon College of
Engineering, Beer-Sheva 84100, Israel
Corresponding author: Arad (Malis) Shoshana (arad@bgu.ac.il)
Current Opinion in Biotechnology 2010, 21:1–7
This review comes from a themed issue on
Evironmental biotechnology
Edited by Sharon Borglin and John van der Meer
0958-1669/$ – see front matter
# 2010 Elsevier Ltd. All rights reserved.
DOI 10.1016/j.copbio.2010.02.008
Introduction
The biotechnological potential of natural polysaccharides
is currently gaining increased recognition as a result of
two parallel, seemingly unrelated, processes—the
tendency of global markets to switch from synthetic to
natural products and a growing understanding of the
functions of sulfated sugars and of the importance of
glycosylation in the post-genomic era. In this context,
the polysaccharides of seaweeds have been under inves-
tigation for many years, but those of the microalgae
remain almost unstudied and elucidating the role of these
complex sugars in cell metabolism poses an exciting
challenge. This review is thus dedicated to the infor-
mation that is available on red microalgal cell-wall
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polysaccharides and their potential biotechnological
applications.
Polysaccharides play significant roles in a variety of func-
tions in the cells of different organisms. In algae, poly-
saccharides serve mainly as storage and structural
molecules. In seaweeds, the structural cell-wall polysac-
charides usually consist of an outer amorphous mucilage
matrix, commonly made up of linear sulfated galactan
polymers (carrageenans, agarans, and alginates) and an
inner rigid component, cellulose fibrils. In the red micro-
algae, the cell walls lack this cellulose microfibrillar
component; rather they are encapsulated within a sul-
fated polysaccharide in the form of a gel [1]. During
growth in a liquid medium, the external part of the
polysaccharide undergoes dissolution from the cell sur-
face into the medium (soluble fraction) [2,3], whereas
most of the polysaccharide (50–70%) remains attached
to the cell (bound fraction). A variety of functions have
been suggested for the red algal cell wall: mechanical
support [1], biorecognition [4], and ion-exchange capacity
[5]; In the red microalgae, the polysaccharide supplies the
cells with environmental protection: the gel structure
protects against desiccation; its stability to temperature,
pH, and salinity [3,6] protects against environmental
extremes, and its antioxidant activity is probably used
as a free radical scavenger [7,8].
The Arad laboratory has taken a multidisciplinary
approach to developing the biotechnology of red micro-
algae. This effort requires the coordination of various
disciplines: chemistry (composition and structure), physi-
ology (effect of environmental conditions), biochemistry
(biosynthesis and sulfation pathways), biotechnology
(applications and bioactivities) [9,10,11], and bioen-
gineering a commercial/large-scale cultivation system
[9,10,12]. Since modern biotechnology demands mol-
ecular-genetic studies, we have made significant progress
in the field of red microalgal genomics by establishing
expressed sequence tag (EST) databases of two species of
red microalgae, Porphyridium sp. and Dixoniella grisea [13],
and in the development of molecular-biology tools
[11,13,14].
Chemical characterization
The chemical characteristics of red algal cell walls have
been investigated mainly in seaweeds, with knowledge
about the chemical structure and characteristics of red
microalgae being more limited. This lag is mainly due to
the complexity of the red microalgal polysaccharides and
Current Opinion in Biotechnology 2010, 21:1–7
COBIOT-715; NO. OF PAGES 7
2 Evironmental biotechnology
to the lack of specific enzymes that degrade them [6,9,15].
The studies that have been performed on the red unicells
have been devoted mainly to four species from different
habitats: Porphyridium sp. (seawater), P. cruentum (sea-
water), P. aerugineum (fresh water), and Dixoniella grisea
(brackish water). The soluble cell-wall polysaccharides of
the different species have a common structural feature—
galactan heteropolymers (molar mass 2–7  106 g mol1)
that contain sulfate residues [3,16–19]. The polysacchar-
ides are anionic owing to the presence of GlcA and half-
ester sulfate groups. In all the species studied, the main
sugars of the polymers are xylose, glucose, and galactose,
but in different ratios. Additional minor sugars – meth-
ylated sugars, mannose, arabinose, and ribose – have also
been detected. The polymers have different sulfate con-
tents (1–9%, w/w), with the sulfate groups being attached
to glucose and galactose in the 6 or 3 position [20]. The
soluble polysaccharides of the different species have a
common basic building block composed of aldobiouronic
acid 3-O-(a-D-glucopyranosyluronic acid)-L-galactopyra-
nose disaccharide [21,22]. Recently, the Arad group has
shown for Porphyridium sp. that this building block is part
of a larger linear building block that contains (1 ! 2 or
1 ! 4)-linked xylopyranosyl, (1 ! 3)-linked galactopyr-
anosyl, and (1 ! 3)-linked glucopyranosyl or glucopyra-
nosyluronic acid residues [23]. One of the proposed
structures of this larger building block is given in
Figure 1.
An anionic polymer separated from the bound polysac-
charide of Porphyridium sp. [24] was found to contain
three major neutral monosaccharides, Xyl, Glc and Gal,
and GlcA. Uronic degradation of this polymer yielded two
oligosaccharides, which differ from the aldobiouronic acid
unit described above.
Very intense research in the Arad laboratory revealed that
there are several proteins bound non-covalently to the
Figure 1
Proposed structure of a linear building block in the Porphyridium sp. polysaccharide [23]. Reprinted with permission from Elsevier.
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cell-wall polysaccharide of Porphyridium sp., the most
prominent being a 66 kDa glycoprotein consisting of a
polypeptide of approximately 58 kDa and a glycan moiety
of approximately 8 kDa [25,26]. Sequencing of a cDNA
clone encoding the 66-kDa glycoprotein revealed that
this is a novel protein, with four potential N-glycan sites,
which does not show similarity to any protein in public-
domain databases or in our in-house EST database of D.
grisea [25,26]. These findings differ from previous
reports of a glycoprotein covalently bound to the cell-
wall polysaccharide of P. cruentum [27,28]. The glycan
structure of moieties attached to proteins in the cell-wall
polysaccharides of various red microalgae are currently
under investigation, indicating novel N-glycan structures
that have not been shown in any other organisms (Oshrat
Ontman, personal communication).
Physicochemical characterization
One of the main characteristics of the red microalgal
polysaccharides that makes them suitable for industrial
applications is their fluid-dynamic behavior
[9,10,13,17,29–37]—highly viscous aqueous solutions
at relatively low polymer concentrations, yielding rheo-
logical properties comparable with industrial polysacchar-
ides, for example, xanthan [17,29–31]. Aqueous solutions
of Porphyridium sp. polysaccharide were found to be
stable (as reflected by their viscosity) when exposed
to a wide range of pH values (2–9), temperatures
(30–120 8C), and salinities [6,32].
An intrinsic viscometry study of dilute solutions of the
soluble fraction of Porphyridium sp. polysaccharide
showed that the stiffness of the polymer chains is in
the same range as that of xanthan gum and DNA [34].
It was suggested that the biopolymer chain molecules
adopt an ordered conformation in solution and that
the polysaccharide has the form of a double or triple
helix [34]. X-ray diffraction studies revealed that the
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Red microalgal cell-wall polysaccharides: biotechnological aspects Arad and Levy-Ontman 3
polysaccharide is composed of an oriented, single, two-
fold, helical structure of pitch 1.6 nm, with extended
regions having a regular chemical repeat [35]. The poly-
saccharide solutions showed marked shear thinning beha-
vior with no evidence of a Newtonian plateau. At higher
concentrations (1%) heating caused visible gelation
accompanied by syneresis, which was reversible upon
cooling. It was also shown that transition upon heating
of the solutions is reversible and sharp from a weak to a
strong elastic gel network. This rare phenomenon appears
to be mediated by hydrophobic interaction in addition to
aggregation of single helical chains of the polymer. The
biotechnological potential of the polysaccharide is further
enhanced by findings that it was superior to hyaluronic
acid as a lubricant in terms of friction reduction, adsorp-
tion and stability [32–37].
Cell-wall polysaccharide formation
In contrast to the cell-wall polysaccharides of seaweeds,
which are characterized by an organized structure, com-
posed of repeating disaccharide blocks, the polysacchar-
ide structure of the red microalgae is more complex.
Various approaches have been taken to elucidate cell-
wall formation in red microalgae; these include the use of
synchronized cultures, cell-wall-modified mutants,
inhibitors of polysaccharide formation, carbon partition-
ing and elucidation of sulfation pathways, and glyco-
protein formation, as described below.
Polysaccharide formation in synchronized cultures
It was previously suggested that the polysaccharide is
secreted to the cell surface by membrane-mediated ex-
ocytosis [38]. By following cell-wall formation during the
cell cycle of Porphyridium sp. and D. grisea in synchro-
nized cultures, an intermediate polysaccharide complex
of 0.5  106 Da containing xylose was detected at the
beginning of the cell cycle (hour 2) [39,40]. It appears that
this sulfated poly-xylose molecule polymerizes further,
incorporating other sugars to produce higher molecular
weight intermediates (molecular masses of 0.5–
2  106 Da at hours 4–6), which finally polymerize extra-
cellularly at hour 8 to produce the cell-wall polysacchar-
ide [39,41].
Cell-wall modified mutants
The herbicide 2,6-dichlorobenzonitrile (DCB), which is
known to inhibit cellulose biosynthesis, was found to
inhibit growth and polysaccharide production in Porphyr-
idium sp. [40,42] and D. grisea [43]. Spontaneous DCB-
resistant D. grisea mutants with modified cell-wall com-
positions and modified characteristics, but with sulfate
and protein contents similar to those of the wild type,
were isolated [43]. In Porphyridium sp., it was shown that
DCB inhibits cell-wall regeneration in protoplasts, and a
number of Porphyridium sp. mutants have been isolated,
all with modified cell-wall compositions that differ from
one another [40,42].
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Formation of the sulfated polysaccharide in the Golgi
apparatus
Using the inhibitor brefeldin A (BFA) it was shown that
polysaccharide biosynthesis takes place through the Golgi
system [44].
Carbon partitioning
By adding 14C-floridoside (a disaccharide composed of
Gal and glycerol) to a culture of whole cells or to a crude
extract of a cell-free system, it was shown that Porphyr-
idium cells assimilate and metabolize floridoside. It was
therefore suggested that the carbon metabolic pathway in
Porphyridium sp. passes through the photoassimilatory
product floridoside, which, in turn, channels the fixed
carbon toward the synthesis of sulfated cell-wall poly-
saccharide according to physiological conditions, for
example, nitrogen starvation [45,46]. Thus, floridoside
functions as a dynamic carbon pool used by the cells as a
carbon precursor in the biosynthesis of starch and the cell-
wall polysaccharide [45,46]. It was further suggested that
the polysaccharide synthesized inside the cells might be
transferred outside the cells into the medium via two
different pathways: directly or by solubilization of the cell
wall into the medium [10,44].
Sulfation
Sulfation of polysaccharides is limited to red and brown
algae and to mammals [47]. Since it has been hypothes-
ized that sulfate is the bioactive group of the red micro-
algal polysaccharides, focus was directed toward
understanding the process. The mode of sulfation of
the cell-wall polysaccharide of Porphyridium sp. was stu-
died by incorporation of sulfur from Na235SO4 or
[35S]cysteine into the cell-wall polysaccharide [48].
The findings implied that in addition to the commonly
accepted ‘inorganic’ sulfation pathway, there might be
another sulfation pathway in which cysteine can serve as
the sulfur donor [48]. This study was followed up with
the characterization of the enzyme sulfotransferase,
which is responsible for the attachment of sulfur to the
cell-wall polysaccharide. The sulfotransferase gene was
identified (in the ESTs), and a biochemical assay was
developed to facilitate its functional characterization [49].
66-kDa glycoprotein
Sequencing of a cDNA clone encoding the 66-kDa glyco-
protein attached to Porphyridium sp. polysaccharide
revealed that the glycoprotein shows some structural sim-
ilarities to protein superfamilies in the SCOP databases,
within the carbohydrate-binding domain (CBD), namely,
glycosyltransferases, pectin lyase-like, sialidases, and
conA-like lectins/glucanases, indicating a possible role of
the 66-kDa glycoprotein in synthesis/modification of the
cell-wall polysaccharide [25,26]. In addition, the N-ter-
minus and one internal peptide of the 66-kDa protein
shows homology to endo-b-1,4-xylanase [26]. Moreover,
the 66-kDa protein was found in the intermediate cell-wall
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4 Evironmental biotechnology

polysaccharide complex of 0.5  106 Da mentioned above
[39,40] and in the cell-wall modified mutants [26]. These
observations and the strong association of the glycoprotein
with the cell-wall polysaccharide suggest that the 66-kDa
protein is involved in the initial stages of cell-wall poly-
saccharide formation [25,26].
Biotechnological aspects
The increasing market demand for natural polysacchar-
ides for the food, cosmetics, and pharmaceutical indus-
tries cannot be met by currently available conventional
sources—red and brown macroalgae. These traditional
sources of polysaccharides, which are usually harvested
from their natural habitats [50,51], are being depleted by
intensive harvesting and detrimental environmental con-
ditions. An attractive alternative may be found in the
sulfated polysaccharides of the red microalgae, which
offer a vast range of potential applications for a variety
of industries [3,9,10,11,13,52,53]. Moreover, various
significant applications are under development.
The unique rheological properties of red microalgal poly-
saccharides (viscoelasticity) may be exploited for a variety
of applications. Thus, owing to the superiority of red
microalgal sulfated polysaccharides over hyaluronic acid,
that is, stability in the body (resistance to hyaluronidase),
their adsorption properties and their superior rheological
characteristics, they make good candidates as water-
soluble lubricants and other biolubricating fluids and
additives to the synovial fluid of joints [32,36]. New
developments of these applications are underway. In
parallel, the fluid-dynamic behavior of the polysacchar-
ides can be exploited in tertiary oil recovery: the poly-
saccharides have been used as thickening agents for
driving fluids to enhance recovery of petroleum trapped
in the pores of reservoir rocks [29–31].
against a variety of animal viruses [63–67,68,69]. The
Porphyridium sp. sulfated polysaccharide exhibited anti-
viral activity against Herpes simplex viruses (type 1 and 2)
and Varicella zoster virus [66,67,68] and displayed in vitro
inhibition of the replication of hemorrhagic septicemia
virus (VHSV) and African swine fever virus (ASFV) [69].
The fact that the Porphyridium sp. polysaccharide is not
toxic [68], as compared with other sulfated sugars,
makes it a valuable candidate for further pharmacological
developments, especially for topical applications.
The Arad group has hypothesized that the bioactive
group is the sulfate group, based on the following obser-
vations: Among the various red microalgal species, the
highest antiviral activity was found in the polysaccharide
having the highest sulfate content (highest in Porphyr-
idium sp., 9% sulfate and the lowest in P. aerugineum with
<1% sulfate). This hypothesis was indeed validated by
experimental findings: a direct correlation was shown
between the polysaccharide’s sulfate content and its
antiviral activity against herpes viruses: Increasing the
sulfate content of the polysaccharide by chemical
methods significantly enhanced its antiviral activities
(Arad, S, personal communication). While blocking the
sulfate groups (by quaternization) [70], significantly
decreased antiviral activity.
The polysaccharide of Porphyridium sp. was found to have
anti-inflammatory, anti-irritating [71], and antioxidant
[7] activities. Owing to these bioactivities, this sulfated
polysaccharide has already been introduced into a wide
range of cosmetic products of a leading global cosmetics
company, and additional developments are underway.
Figure 2

In addition to their biolubricant activities, the red micro-

algal polysaccharides exhibit various bioactivities that
have nutritional, medicinal, and cosmetic significance.
Animal feeding experiments have shown that rodents
whose diets are supplemented with low concentrations
of red microalgal polysaccharides have considerably low-
ered levels of serum cholesterol, triglycerides, and very
low-density lipoprotein levels [54–56,57] with no evi-
dence of toxic side effects. It was thus suggested that the
polysaccharides act as dietary fibers [54–56] and can be
valuable in a functional food [56].

Porphyridium sp. cell-wall sulfated polysaccharide was

shown to have antitumor and antiviral activities. The
antitumor activity was demonstrated against sarcoma
inoculated in the peritoneal cavity of mice [58] and
against myeloid Graffi tumor, both in vitro and in vivo
in hamsters [59]. Sulfated polysaccharides were shown to
have antiviral activities [60–62]. The antiviral activity of
red microalgal polysaccharides has been demonstrated Large-scale facility of red microalgae for polysaccharide production.

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Red microalgal cell-wall polysaccharides: biotechnological aspects Arad and Levy-Ontman 5
To facilitate commercial scale production of the poly-
saccharide, it was necessary to develop the biotechnology
that is specifically directed for red microalgae that secrete
cell-wall polysaccharides into the growth medium. The
polyethylene vertical bioreactors [9,10,11,12] that
were developed by the Arad group are currently in use
for large-scale production of Porphyridium sp. polysacchar-
ide (Figure 2) by the multinational company Frutarom,
which is situated in the Negev area of Israel.
The bioactivities described above bear witness to the
potential of novel red microalgal polysaccharides, with
their unique characteristics, in the development of bio-
technological applications [52], mainly for the healthcare
and pharmaceutical industries. For most of the potential
applications, the market is still developing.
References and recommended reading
Papers of particular interest, published within the annual period of
review, have been highlighted as:
 of special interest
 of outstanding interest
1. Bold HC, Wynne MJ: Introduction to the Algae: Structure and
ReproductionPrentice Hall Inc.; 1985.
2. Ramus J: Rhodophyte unicells: biopolymer, physiology and
production. In Algal Biomass Technologies—An
Interdisciplinary Perspective. Edited by Barclay WR, McIntosh
RP. Cramer J; 1986: 51-55.
3. Arad (Malis) S: Production of sulfated polysaccharides from red
unicellular algae. In Algal Biotechnology—An Interdisciplinary
Perspective. Edited by Stadler T, Mollion J, Verduset MC. Elsevier
Applied Science; 1988:65-87.
4. Ucko M, Shrestha RP, Mesika P, Bar-Zvi D, Arad (Malis) S:
Glycoprotein moiety in the cell wall of the red microalga
Porphyridium sp. (Rhodophyta) as the biorecognition site for
the Crypthecodinium cohnii-like dinoflagellate. J Phycol 1999,
35:1276-1281.
5. Geresh S, Shefer A, Arad (Malis) S: A chemically cross-linked
polysaccharide from a red microalga as a potential ion
exchanger and adsorbant of metal ions. J Carbohydr Chem
1997, 16:703-708.
6. Ucko M, Cohen E, Gordin H, Arad (Malis) S: Relationship
between the unicellular red alga Porphyridium sp. and its
predator the Gymnodinium sp. Appl Environ Microbiol 1989,
55:2290-2294.
7. Tannin-Spitz T, Bergman M, van-Moppes D, Grossman S, Arad
(Malis) S: Antioxidant activity of the polysaccharide of the red
microalga Porphyridium sp. J Appl Phycol 2005, 17:215-222.
8. Chen B, Wenlang Y, Huang J, Yu Y, Chen W: Isolation and
antioxidant property of the extracellular polysaccharide from
Rhodella reticulata. World J Microbiol Biotechnol 2009 doi:
10.1007/s11274-009-0.240.
9. Arad (Malis) S: Polysaccharides of red microalgae. In
Chemicals from Microalgae. Edited by Cohen Z. Taylor and
Francis; 1999:282-291.
10. Arad (Malis) S, Richmond A: Industrial production of microalgal
 cell-mass and secondary products—species of high potential:
Porphyridium sp.. In Handbook of Microalgal Culture:
Biotechnology and Applied Phycology. Edited by Richmond A.
Blackwell Publishing Ltd.; 2004:289-297.
Large-scale production aspects and their importance for commercial
applications are discussed.
11. Lapidot M, Shrestha RP, Weinstein Y, Arad (Malis) S: Red
 microalgae: from basic know-how to biotechnology. In
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Please cite this article in press as: Arad SM, Levy-Ontman O. Red microalgal cell-wall polysaccharides: biotechnological aspects, Curr Opin Biotechnol (2010), doi:10.1016/j.copbio.2010.02.008
Cellular Origin, Life in Extreme Habitats and Astrobiology: Red
Algae in Genomic Age. Edited by Seckbach J, Chapman DJ.
Springer; 2010.
This review presents for the first time genomic and molecular aspects of
red microalgal cells.
12. Cohen E, Arad (Malis) S: A closed system for outdoor cultivation
of Porphyridium. Biomass 1989, 18:59-67.
13. Arad S, Weinstein Y: Novel lubricants from red microalgae:
interplay between genes and products. Biomedic (Israel) 2003,
1:32-37.
14. Hoef-Emden K, Shrestha RP, Weinstein Y, Melkonian M,
 Lapidot M, Arad (Malis) S: Actin phylogeny and intron
distribution in the Bangiophyte red algae (Rhodoplantea). J
Mol Evol 2005, 61:360-371.
Lack of an intron in the red algal genome is of thought-provoking interest.
15. Arad (Malis) S, Keristovsky G, Simon B, Barak Z, Geresh S:
Biodegradation of the sulphated polysaccharide of
Porphyridium by soil bacteria. Phytochemistry 1993, 32:287-290.
16. Percival EP, Foyle RAJ: The extracellular polysaccharides of
Porphyridium cruentum and Porphyridium aerugineum.
Carbohydr Res 1979, 72:165-176.
17. Geresh S, Arad (Malis) S: The extracellular polysaccharides of
the red microalgae: chemistry and rheology. Bioresour Technol
1991, 38:195-201.
18. Dubinsky O, Simon B, Karamanos Y, Geresh S, Barak Z, Arad
(Malis) S: Composition of the cell-wall polysaccharide
produced by the unicellular red alga Rhodella reticulata. Plant
Physiol Biochem 1992, 30:409-414.
19. Heaney-Kieras J, Chapman DJ: Structural studies on the
extracellular polysaccharide of the red alga Porphyridium
cruentum. Carbohydr Res 1976, 52:169-177.
20. Lupescu N, Arad (Malis) S, Geresh S, Bernstein M, Glazer R:
Structure of some sulfated sugars isolated after acid
hydrolysis of the extracellular polysaccharide of Porphyridium
sp. a unicellular red alga. Carbohydr Res 1991, 210:349-352.
21. Jaseja M, Perlin AS, Dubinsky O, Christiaen D, (Malis) Arad S,
Glaser R: NMR structure determination of 3-O-(alpha-D-
glucopyranosyluronic acid)-L-galactopyranose, an
aldobiuronic acid isolated from the unicellular red alga
Rhodella reticulata. Carbohydr Res 1989, 186:313-319.
22. Geresh S, Dubinsky O, Arad (Malis) S, Christiaen D, Glaser R:
Structure of 3-O-(alpha-D-glucopyranosyluronic acid)-L-
galactopyranose, an aldobiouronic acid isolated from the
polysaccharides of various unicellular red algae. Carbohydr
Res 1990, 208:301-305.
23. Geresh S, (Malis) Arad S, Levy-Ontman O, Zhang W, Tekoah Y,
 Glaser R: Isolation and characterization of poly- and
oligosaccharides from the red microalga Porphyridium sp.
Carbohydr Res 2009, 344:343-349.
Additional information on sugar-sequence in the complex polysaccharide
is presented.
24. Gloaguen V, Ruiz G, Morvan H, Mouradi-Givernaud A, Maes E,
Krausz P, Strecker G: The extracellular polysaccharide of
Porphyridium sp.: an NMR study of lithium-resistant
oligosaccharidic fragments. Carbohydr Res 2004, 339:97-103.
25. Shrestha RP, Weinstein Y, Bar-Zvi D, Arad (Malis) S: A
 glycoprotein noncovalently associated with cell-wall
polysaccharide of the red microalga Porphyridium sp.
(Rhodophyta). J Phycol 2004, 40:568-580.
The complex cell-wall polysaccharide contains a 66 kDa glycoprotein,
composed of protein and a unique glycan moiety. The protein part
belongs to the carbohydrate-binding domain (CBD). It is suggested that
the glycoprotein, in addition to being a recognition site, is involved in red
microalgal cell-wall biosynthesis.
26. Shrestha RP: A non-covalently bound cell-wall glycoprotein of
the red microalga Porphyridium sp.: characterization and
functions. Ph.D. Thesis, Submitted to Ben-Gurion University of
the Negev, Israel; 1999.
27. Heaney-Kieras J, Roden L, Chapman DJ: The covalent linkage of
protein to carbohydrate in the extracellular protein-
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6 Evironmental biotechnology
polysaccharide from the red alga Porphyridium cruentum.
Biochem J 1977, 165:1-9.
28. Heaney-Kieras J, Swift H: Electron microscopy of extracellular
polysaccharide of the red alga Porphyridium cruentum.
Glycoconjug Res 1979, 1:165-166.
29. Savin JG: Oil recovery process employing thickened aqueous
driving fluid. US Patent 4,079,544, filed April 28, 1976 and issues
March 28, 1978.
30. Ramus J, Kenney BE, Shaughnessy EJ: Drag reducing
properties of microalgal exopolymers. Biotechnol Bioeng 1989,
33:550-557.
31. Ramus J, Kenney BE: Shear degradation as a probe of
microalgal exopolymer structure and rheological properties.
Biotechnol Bioeng 1989, 34:1203-1208.
32. Arad (Malis) S, Rapoport L, Moshkovich A, van-Moppes D,
 Karpasas M, Golan R, Golan Y: Superior biolubricant from a
species of red microalga. Langmuir 2006, 22:7313-7317.
The main characteristic of the red microalgal polysaccharide – its resis-
tance – is demonstrated vis-à-vis that of hyaluronic acid.
33. Ginzberg A, Korin E, Arad (Malis) S: Effect of drying on the
biological activities of a red microalgal polysaccharide.
Biotechnol Bioeng 2008, 99:411-420.
34. Eteshola E, Gottlieb M, Arad (Malis) S: Dilute solution viscosity of
red microalga exopolysaccharide. Chem Eng Sci 1996,
51:1487-1494.
35. Eteshola E, Karpasas M, Arad (Malis) S, Gottlieb M: Red
microalga exopolysaccharides: 2. Study of the rheology,
morphology and thermal gelation of aqueous preparations.
Acta Polym 1998, 49:549-556.
36. Gourdon D, Lin Q, Oroudjev E, Hansma H, Golan Y, Arad S,
Israelachvili J: Adhesion and stable low friction provided by a
subnanometer-thick monolayer of a natural polysaccharide.
Langmuir 2008, 24:1534-1540.
37. Yaron A, Cohen E, Arad (Malis) S: Stabilization of Aloe vera gel
by interaction with sulfated polysaccharides from red
microalgae with xanthan gum. J Agr Food Chem 1993,
40:1316-1320.
38. Ramus J: The production of extracellular polysaccharide by
the unicellular red alga Porphyridium aerugineum. J Phycol
1972, 8:97-111.
39. Simon-Bercovitch B, Bar-Zvi D, Arad (Malis) S: Cell-wall
formation during the cell cycle of Porphyridium sp.
(Rhodophyta). J Phycol 1999, 35:78-83.
40. Bercovitch-Simon B: Cell-wall formation in the red microalga
Porphyridium sp. Ph.D. Thesis, Submitted to Ben-Gurion
University of the Negev, Israel; 1997.
41. Cohen (Katz) A, Arad (Malis) S: Biosynthesis of the cell-wall
polysaccharide in the red microalga Rhodella reticulata. Isr J
Plant Sci 1998, 46:144-153.
42. Arad (Malis) S, Kolani R, Simon-Berkovitch B, Sivan A: Inhibition
 by DCB of cell-wall polysaccharide formation in the red
microalga Porphyridium sp. (Rhodophyta). Phycologia 1994,
33:58-162.
Production of cell-wall modified mutants resistant to DCB is a valuable
tool for understanding of cell-wall biosynthesis.
43. Arad (Malis) S, Dubinsky O, Simon B: A modified cell wall mutant
of the red microalga Rhodella reticulata resistant to the
herbicide 2,6-dichlorobenzonitrile. J Phycol 1993,
29:309-313.
44. Keidan M, Friedlander M, Arad (Malis) S: Effect of Brefeldin A on
cell-wall polysaccharide production in the red microalga
Porphyridium sp. (Rhodophyta) through its effect on the Golgi
apparatus. J Appl Phycol 2009, 21:707-717.
45. Li SY, Lellouche JP, Shabtai Y, Arad S: Fixed carbon partitioning
in the red microalga Porphyridium sp. (Rhodophyta). J Phycol
2001, 37:289-297.
46. Li SY, Shabtai Y, Arad (Malis) S: Floridoside as a carbon
 precursor for the synthesis of cell-wall polysaccharide in the
Current Opinion in Biotechnology 2010, 21:1–7
Please cite this article in press as: Arad SM, Levy-Ontman O. Red microalgal cell-wall polysaccharides: biotechnological aspects, Curr Opin Biotechnol (2010), doi:10.1016/j.copbio.2010.02.008
red microalga Porphyridium sp. (Rhodophyta). J Phycol 2002,
38:931-938.
The paper shows the involvement of the disaccharide floridoside in cell-
wall biosynthesis.
47. Gao Y, Schofield O, Leustek T: Characterization of sulfate
assimilation in marine algae focusing on the enzyme 50 -
adenylylsulfate reductase. Plant Physiol 2000, 123:1087-1096.
48. Keidan M, Broshy H, van Moppes D, Arad (Malis) S: Assimilation
 of sulphur into the cell-wall polysaccharide of the red
microalga Porphyridium sp. (Rhodophyta). Phycologia 2006,
45:505-511.
The authors show that there might be an alternative pathway for assim-
ilation of sulfur into the polysaccharide, through cysteine.
49. Plesser L, Lapidot M, Weinstein Y, Arad (Malis) S:
Sulfotransferase of red microalgae: a molecular and
biochemical study. Poster presented at the 8th Marine
Biotechnology Conference; Eilat, Israel, March: 2007.
50. Gellenbeck K, Chapman D: Seaweed uses: the outlook for
mariculture. Endeavour 1983, 7:31-37.
51. Usov AI, Smirnova GP, Klochkova NG: Polysaccharides of Algae:
55.1 Polysaccharide Composition of Several Brown Algae
from Kamchatka. Russian Journal of Bioorganic Chemistry
(Bioorganicheskaya Khimiya) (Formerly: Soviet Journal of
Bioorganic Chemistry) 2001, 27:444-448.
52. Arad (Malis) S, Spharim I: Production of valuable products
from microalgae: an emerging agroindustry. In Agricultural
Biotechnology. Edited by Altman A. Marcel Decker Inc.; 1998:
629-643.
53. Arad (Malis) S: Biotechnology for production of sulfated
polysaccharides from red microalgae. In Cost 49 Technology
and Biotechnology of Algal Polysaccharides: Future Trends. Edited
by Cre V, Rizzo R, Skjåk-Braek G. European Commission, EUR
18951; 1999:127-142.
54. Dvir I, Geva O, Chayoth R, Sod-Moriah U, Shany S, Arad S,
Madar Z: Polysaccharides and algal biomass as new sources
of dietary fibers and their physiological effects in rats. FASEB J
1996, 10:3012-13012.
55. Dvir I, Chayoth R, Sod-Moriah U, Shany S, Nyska A, Stark AH,
Madar Z, Arad (Malis) S: Soluble polysaccharide and biomass of
red microalga Porphyridium sp. alter intestinal morphology and
reduce serum cholesterol in rats. Br J Nutr 2000, 84:469-476.
56. Arad (Malis): Red Microalgae: Potential Nutraceuticals. Invited
lecture at Food in the New Era, Israel; September 2009.
57. Dvir I, Stark AH, Chayoth R, Madar Z, Arad (Malis) S:
 Hypocholesterolemic effects of nutraceuticals produced from
the red microalga Porphyridium sp. Nutrients 2009, 1:156-167
doi: 10.3390/nu1020156.
The paper indicates the effect of feeding with algal biomass – including
the polysaccharides – on lipid metabolism.
58. Sakamoto H, Torada H, Toto K, Nakamura Y, Nakano T,
Yamaguchi T, Sato M, Saito T, Taniguchi A, Yokoyama T et al.:
Biological activity of the polysaccharide produced by the
marine phytoplankton Porphyridium sp. and additive effect of
slag on the polysaccharide production. Tetsu-to-Hagane 2003,
89:475-481.
59. Gardeva E, Toshkova R, Minkova K, Gigova L: Cancer protective
action of polysaccharide, derived from red microalga
Porphyridium cruentum—a biological background. Biotechnol
Biotechnol Equip 2009, 23:783-787.
60. Gonzalez ME, Alarcon B, Carrasco L: Polysaccharides as
antiviral agents: antiviral activity of carrageenan. Antimicrob
Agents Chemother 1987, 31:1388-1393.
61. Biesert L, Suhartono H, Winkler I, Meichsner C, Helsberg M,
Hewlett G, Klimetzek V, Molling K, Schlumberger HD, Schrinner E
et al.: Inhibition of HIV and virus replication by polysulfated
polyxylan–HOE/BAU 946, a new antiviral compound. AIDS
1988, 2:449-457.
62. Sugawara I, Itoh W, Kimura S, Mori S, Shimada K: Further
characterization of sulfated homopolysaccharides as anti-HIV
agents. Experientia 1989, 45:996-998.
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Red microalgal cell-wall polysaccharides: biotechnological aspects Arad and Levy-Ontman 7
63. Ehresman DW, Deig EF, Hatch MT: Antiviral properties of algal
polysaccharides and related compounds. In Marine Algae in
Pharmaceutical Science. Edited by Hoppe HA, Levring T. De
Gruyter; 1979:293-302.
64. Minkova K, Michailov Y, Toncheva-Panova T, Houbavenska N:
Antiviral activity of Porphyridium cruentum polysaccharide.
Pharmazie 1996, 51:3-7.
65. Talyshinsky M, Souprun Y, Huleihel M: Anti-viral activity of red
microalgal polysaccharides against retroviruses. Cancer Cell
Int 2002, 2:1-8.
66. Huleihel M, Ishanu V, Tal J, Arad (Malis) S: Activity of
Porphyridium sp polysaccharide against herpes simplex
viruses in vitro and in vivo. J Biochem Biophys Methods 2002,
50:189-200.
67. Huleihel M, Vladimir Z, Tal J, Arad S: Antiviral effect of red
microalgal polysaccharides on Herpes simplex and Varicella
zoster viruses. J Appl Phycol 2001, 13:127-134.
68. Arad (Malis) S, Ginzberg A, Huleihel M: Antiviral activity of
 sulfated polysaccharides of marine red algae. In Recent
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Advances in Marine Biotechnology: Biomaterials from Aquatic and
Terrestrial Organisms. Edited by Fingerman M. Science Publishers
Inc. Enfield; 2006:37-62.
This review describes the potential of the antiviral activity of sulfated
polysaccharides for the development of pharmaceutical applications.
69. Fabregas J, Garcı́a D, Fabregas J, Garcia D, Fernandez-Alonso M,
Rocha AI, Gómez-Puertas P, Escribano JM, Otero A, Coll JM: In
vitro inhibition of the replication of haemorrhagic septicaemia
virus and African swine fever virus by extracts from marine
microalgae. Antiviral Res 1999, 44:67-73.
70. Geresh S, Dawadi RP, Arad (Malis) S: Chemical modifications of
biopolymers: quaternization of the extracellular
polysaccharide of the red microalga Porphyridium sp.
Carbohydr Polym 2000, 43:75-80.
71. Matsui MS, Muizzuddin N, Arad S, Marenus K: Sulfated
 polysaccharides from red microalgae have anti-inflammatory
properties in vitro and in vivo. Appl Biochem Biotechnol 2003,
104:13-22.
The anti-inflammatory activities of the sulfated polysaccharides have
opened the door to large cosmetic and pharmaceutical applications.
Current Opinion in Biotechnology 2010, 21:1–7