hungarian universities” tÁmop-4.1.1.c-13/1/konv-2014-0001 · education for strengthening the...
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Biomedical potential of cyanobacteria and algae
István-Zoltán VassInstitute of Plant Biology
November 23, 2016
„Practice-oriented, student-friendly modernization of the biomedical education for strengthening the international competitiveness of the rural Hungarian universities”TÁMOP-4.1.1.C-13/1/KONV-2014-0001
Cyanobacteria and algae are oxygenic photosynthetic organisms
CyanobacteriaGeneral informationBiotechnological importanceBiomedical potential
AlgaeGeneral informationBiotechnological importanceBiomedical potential
Importance of photosynthesis
Based on the representative slide of Ghada Ajlani
Cyanobacteria
Oxygen producing photosynthetic bacteriaAncestor of plastidsHabitant of extreme environments
(terrestial, freshwater, marine and hypersaline environments)Unicellular, Filamentous Nitrogen fixationMany strains genetically accessibleGenetic modification
Unicellular model organisms
Synechocystis sp. PCC6803 Synechococcus sp. PCC7942
Filamentous
Anabaena sp. PCC7120 Spirulina platensis
Biotechnical application
- Bioremediation (Chromium, Lindane, Radioactive Cesium)
- Biosensors
- Nitrogenous fertilizers
- Biological production of hydrogen and polyesters
- Edible cyanobacteria
-Nutritional benefits of cyanobacteria
- Basic research
- Medicinal drugs
Biosensor
Whole cell reporter organisms
Recombinant bioluminescent bacterial sensors
Bacterial resistance mechanisms against metal or metalloid cations
(Nickel, Cobalt, Zinc)
Nitrogenousn fertilizers
Cell diferenciation
N2 Fixation
5-10% of all cells
Unable to divide again
FtsZ is dowregulated( controlled at a post-transcriptional level)
The DnaA protein, which is the initiator of DNA replication, is downregulated in heterocysts.
Heterocyts
http://foodtank.com/news/2014/02/cyanobacterial-bio-fertilizer-natures-own-solution-for-improved-soil-fertil
http://agritech.tnau.ac.in/org_farm/orgfarm_biofertilizertechnology.html
- Environmental friendly, no CO2 emission, renewable- Produced by several cyanobacteria- Nitrogenase in heterocyst
16 ATP + 16 H2O + N2 + 10 H+ + 8e- → 16 ADP + 16 Pi + 2 NH4+ + H2
Potential Hydrogen production
• Produced by cyanobacteria→ degradable• Polyhydroxyalkanoates (PHAs), Polyhydroxybutyrate (PHB)
Polyester
http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2672.2008.03918.x/abstract
HO OH
CH3 O
n
• Protein: ~50-65 %• Lipids: ~4-7 %, γ-linolenic acid (→ arachidonic acid, prostaglandins)• Carbohydrates ~15-20%• Polysaccharides : „Immulina”: immunostimulating polysaccharides• Vitamins: β-carotin (vitamin A)
vitamin B12 (more than in liver)vitamin E (comparable with wheat germ)
• Minerals ~3-7 %: Fe, Ca, Mg, K
Edible cyanobacteria
Nutrition benefit
Human food and animal feed
http://www.maxwellsci.com/print/ajfst/v6-303-307.pdf
Spirulina
http://www.algaeindustrymagazine.com/special-report-spirulina-part-2-first-human-consumption-and-cultivation/
http://www.auroville.org/contents/114
http://www.smartmicrofarms.com/PDF.cfm/EarthFoodSpirulina.pdf
Biomedical potential of cyanobacteria
Modell organismRestriction enzymes (AflII, AflIII, AvaI, AvaII, AvrII, FspI, NspI)Phycobilins used as dyes in immuno assays
Research
http://www.bdbiosciences.com/research/multicolor/spectrumguide/index.jsp
http://www.mobitec.de/probes/docs/sections/0604.pdf
http://www.lifetechnologies.com/hu/en/home/references/molecular-probes-the-handbook/ultrasensitive-detection-technology/phycobiliproteins.html
Secondary metabolites
Hundreds of secondary metabolites were reported from cyanobacteria
Function ?Adaptation to extreme environmentAdvance in competition with other organismsStress defense
Polyketide synthase (PKS)ketosynthase, Acyltransferase, ketoreductase, Dehydratase, Enoyl reductase and Acyl carrier protein domains
Non-ribosomal polypeptide synthetase (NRPS)Aminoacid-activating adenylation, Pepetidyl carrier and Condensation domain
Hybrid PKS - NRPS structure
Hectochlorin – antiproliferative activities againts melanomaantifungal activity againts Candida albicans
Kalkitoxin – potential candidate for development of neuroprotective drugs
Lyngbyabellins – cytotoxic and antifungal
Apratoxin – cytotoxic
Calcium spirulina (Ca-SP) (Spirulina platensis) – Sulfated polysaccharidantiviral (HIV-1, Herpes simplex, influenza-A etc)
Cyanovirin-N (Nostoc ellipsosporum) --- antiviral (interaction with the viral surface envelope glycoproteins )
http://www.ncbi.nlm.nih.gov/Structure/mmdb/mmdbsrv.cgi?uid=19594http://mcl1.ncifcrf.gov/wlo_pubs/177.pdf
Calothrixins – drug development (Malaria, Cancer)
Others (Lipids, pigment molecules)
Phycobiliproteins - phycobilinsanticancerhepatoprotectiveanti-inflammatorycholesterol reducing
Chlorophylls – food additive
Chlorophyll a
Structure was drawn using MarvinSketch http://www.chemaxon.com/marvin/sketch/index.php
Scytonemin – UVA sunscreen
Photolyase – flavoenzyme - photochemoprevention
Mycosporin-like amino acids (MAAs) – Porphyra 334 – UVA protection
Porphyra-334
Dolastatin analogs: cemadotin and TZT-1027 - evaulated in phase II clinical trials – treatment advanced solid tumors
Dolastatin 15
Structure was drawn using MarvinSketch http://www.chemaxon.com/marvin/sketch/index.php
Cryptophycins
Anti-cancer
advenced ovarian cancer
– tumor cells could develop multiple drug resistance (MDR) – active on MDR cells
Curacin A – potent antimitotic, anticancer agent(affect tubulin polymerization)
Immunomodulation
Anti-inflammation
Antiallergenic
Antimitotic
Anticancer
Neuroprotection
http://www.elmatkft.hu/galeria/index.php
AlgaeOxygen producing photosynthetic eukaryotesPlastidsOccur in most habitatsUnicellular, Filamentous Some strains genetically accessibleGenetic modification
http://botany.si.edu/projects/algae/economicuses.htmhttp://www.algaebase.org/
Chlamydomonas reinhardtii
Biotechnical application- Fertilizers
- Energy source
Biofuel production
- Pollution control
Capture fertilizers, Algae scrubber, Sewagetreatment
- Nutrition
http://www.noahhealth.org/chlorella-can-help-make-better-breast-milk/#mpo
http://chlorella.bolt.hu/
http://en.wikipedia.org/wiki/Nori
http://www.seaweed.ie/aquaculture/noricultivation.php
- Basic research
- Medicinal drug development
Vaccine production
Transmission blocking vaccine: Malaria – Pfs25 production C. reinhardtii
Biomedical potential of algae
http://schaechter.asmblog.org/schaechter/2012/07/fishing-with-algae-for-malaria-vaccines.html
Polysaccharide based biomaterials
tissue regenerationcell immobilizationdrug delivery
Red algae
Carrageenans (sulfated galactants) interact with proteins (casein in milk)bind heavy metals – clean contaminated waterIndustrial application (emulsifier, gelling, stabilizing agentclassification: kappa (k), iota (i), lambda (l)
Agar: generic name for seaweed galactantsbulking agent, laxatives, suppositories, capsules, tablets, anticoagulants
k- Carregenan: antioxdant, protection from viral, fungal and bacterial infectionimmobilization of enzymesencapsulation of cells for their in vivo delivery
Structure was drawn using MarvinSketch http://www.chemaxon.com/marvin/sketch/index.php
Green algae
More complex and diverse chemistryantioxidantchelate metalsantiproliferative, antitumoralimmunostimulatingantiviral
Research: drug deliverywound dressingbone tissue engineering
Brown algae
Fucoidanantioxidant, anti-aging, skin protectantIndustrial application:
Cosmetics: acne treatment, hair hydration, tooth pasteFood: dietetic fibers, cholesterol reducer, sports beverage
Biopharmaceutical: antiviral, immunological, anticoagulant, drug delivery, nano materials, tissue engineering
Linear polysaccharides (linked mannuronic and guluronic acid residues)
Oral delivery of bioactive peptides
Therapeutic cell entrapment gel beads as entrapment devices for transplantation of insulin producing cells
Dental impression materialsComponent of product that prevents gastric reflux (Gaviscon)Treatment epidermal and dermal woundsImmunogenic properties
Alginate
Structure was drawn using MarvinSketch http://www.chemaxon.com/marvin/sketch/index.php
Lectins or agglutinins
Carbohydrate-binding proteins
detection of diseases (alteration of glycan synthesis)cell markers for diagnostic purposeenhancing penetration of drugsanti-inflammatoryantinociceptiveantiviralanticancer
Mycosporin-like amino acids MAAs
Sun care products
Halogenated compounds
Polyhalogenated monoterpenes – antimicrobial, antitubercular, anticancer
Palythinol
Palythinol, Palythene, Asterina-330, Shinorine
CarotenoidsProvitamin A, Photoprotection, Skin protection
Astaxanthin – lower risk of cancer
Lutein – inhibit lipid peroxidation - prevent senile dementia
b-carotene – preventing cancer, atherosclerosis, coronary heart disease
Bioactive phenols
Phlorotannins
anti-diabeticanti-cancerantioxidantpotential anti-HIVanti-agingmatrix metalloproteinase inhibitionangiotensin I converting enzyme inhibition
Lipids
Polyunsaturated fatty acids (PUFA)
2D struture of g-linolenic acid
g-linolenic acid – skin, immune systemlinoleic, linolenic acid – prostaglandin synthesis, skin hyperplasiaArachidonic acid – vasoconstrictiveDocosahexaenoic acid – anti-inflammatoryEicosapentaenoic acid – antimicrobial, anti-inflammatory
Structure was drawn using MarvinSketch http://www.chemaxon.com/marvin/sketch/index.php
PerspectivesCompounds isolated from cyanobacteria and algae have extraordinary
chemical diversity, often showing unprecedented chemical structure and displayinteresting biological activity.
They could be a valuable treasure to create new therapeutic agents, sinceconstant need exists for new biomaterials that are biocompatible, efficient and safe.
However the mechanism how they exert their effect needs to be explored,even often the active compounds wait for identification.
Unfortunately after the isolation of the bioactive agents is a long process tobecome consumable nutrition or drug.
There is a high demand for continuous search for these agents and fordetailed studies of their way of action.
Abed R.M.M. et al. 2009 Journal of Applied Microbiology 106: 1-12Belay A. 2002 The Journal of the American Nutraceutical Association 5: 27-48Berardesca E. et al. 2012 Molecular Medicine Reports 5: 570-574Botos I and Wlodawer A. 2003 Cellular and Molecular Life Sciences 60: 277-287Domonkos I. et al. 2013 Progress in Lipid Research 52: 539-561Dubey S.K. et al. 2011 African Journal of Biotechnology 10: 1125-1132Eggen M. and Georg G.I. 2002 Medicinal Research Reviews 22: 85-101El-Bestavy E.A. et al. 2007 International Biodeterioration and Biodegradation 59: 180-192Eriksen N.T. 2008 Applied Microbiology and Biotechnology 80: 1-14 Kannan V. et al. 2010 International Journal of Environmental Sciences 2: 2360-2366Kiss E. et al. 2009 Journal of Biotechnology 142: 31-7Lyra C. et al. 2000 Journal of Applied Microbiology 89: 979-991Mishima T. et al. 1998 Clinical and Experimental Metastasis 16: 541-550Nagarajan M. et al. 2012 Journal of Applied Toxicology 33: 313-349Quintana N. et al. 2011 Applied Microbiology and Biotechnology 91: 471-490Rickards R.W. et al. 1999 Tetrahedron 55: 13513-13520Rohr J. 2006 ACS Chemical Biology 1: 747-750Sasaki H. et al. 2013 Microbes and Environments 28: 466-469Shimizu Y. 2003 Current Opinion in Microbiology 6: 236-243Tan L.T. 2006 Journal of Coastal Development 9: 129-136Torres A. et al. 2006 Photochemical and Photobiological Science 5:432-435
References
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References
Thank you for your attention!
This work is supported by the European Union, co-financed by the European Social Fund, within the framework of " Practice-
oriented, student-friendly modernization of the biomedical education for strengthening the international
competitiveness of the rural Hungarian universities " TÁMOP-4.1.1.C-13/1/KONV-2014-0001 project.