MARINE BIODISCOVERY - Can be defined as the chemical exploration of marine biodiversity, to detect, isolate, characterize, identify and evaluate structurally diverse natural products.
Over the last three decades the Capon Group has established itself as a leader in the field of marine biodiscovery. To support our research we assembled a library of Australian marine invertebrate and algae samples (~2,800), collected by hand from intertidal (0-2 m) and coastal waters (2-30 m), and by off-shore trawling (>50 m), across southern Australia to Antarctica. We designed and implemented many innovative marine biodiscovery protocols, including construction of a fractionated (enriched) extract library formatted in 96 well plates for rapid screening, UPLC-DAD tagging of >50,000 metabolites in this library (the majority new to science), and a raft of streamlined isolation, purification and structure elucidation protocols. In addition to isolating and identifying several thousand marine metabolites, we routinely undertake chemical syntheses of high priority metabolites, to support structure assignments, and advance pharmaceutical and agrochemical biodiscovery (see below).
In addition to publishing our findings (visit Rob Capon and select from Articles, Magazines, Books and Patents), several of our more significant marine biodiscovery achievements remain commercial-in-confidence. These include a marine brown alga-inspired anthelmintic for the treatment of parasite infections in livestock, and a marine sponge-inspired analgesic for the treatment of chronic inflammatory pain. To learn more of our marine drug discovery activities visit Pharmaceutical Biodiscovery and Agrochemical Biodiscovery.
Listed below are several examples of our marine natural product discoveries.
(see Banner Images for chemical structures)
Bistellettazines – These first-in-class terpenyl-pyrrolizidine alkaloids, isolated from a marine sponge, Stelletta sp., collected during scientific trawling operations in the Great Australian Bight, feature an unprecedented framework derived from the biogenic equivalent of a Diels-Alder addition.
(Org Lett, 2008, 10, 4247-4250)
Phorbasins – These first-in-class diterpenyl-taurine alkaloids, isolated from a marine sponge, Phorbas sp., collected during scientific trawling operations in the Great Australian Bight, feature an unprecedented hetercyclic scaffold derived from the biogenetic equivalent of cascading Michael additions.
(Org Biomol Chem, 2008, 6, 3811-3815)
Ianthellidones – These first-in-class pyrrolidone alkaloids, isolated from a marine sponge, Ianthella sp., collected during scientific trawling operations in the Great Australian Bight, are structurally distinct from, but biosynthetically related to co-metabolite lamellarins. The co-metabolite ianthellidones and lamellarins are inhibitors of the aspartic acid protease, Beta-secretase 1 (BACE1), a target for the treatment of neurodegenerative diseases, including Alzheimer’s disease.
(Org & Biomol Chem, 2012, 10, 2656-2663)
5’-Thio-xyloadenosine disulphide – The first reported example of a naturally occurring nucleoside disulfide, and only the second reported example of a natural xylo-nucleoside, isolated from a marine sponge, Trachycladuslaevispiulifer, collected as by-catch during commercial trawling operations in the Great Australian Bight.
(Aust J Chem, 2010, 63, 873-876)
Franklinolides – The first reported example of a polyketide phosphonate diester, isolated from a marine sponge, Halichondria sp., collected during scientific trawling operations in the Great Australian Bight. The franklinolides exhibit complex structural stability issues, and demonstrate for the first time that phosphonate dieters can dramatically enhance innate cytotoxicity.
Bastadins – Rare cyclic tetrapeptides comprised of brominated tyrosine residues, isolated from a Great Barrier Reef marine sponge, Ianthella basta.
(Aust J Chem, 1991, 44, 287-296)
Luffarins – A remarkable array of >30 highly oxygenated terpenes isolated from a marine sponge, Luffariella geometric Kirkpatrick, collected during commercial trawling operations (below 350 m) in the Great Australian bight - aboard the fishing vessel "Comet".
(Aust J Chem, 1992, 45, 1705-1743)
Cometins – New furanosesterterpenes from a marine sponge, Spongia sp., collected during commercial trawling operations (below 150 m) in the Great Australian Bight - aboard the fishing vessel "Comet".
(Aust J Chem, 1992, 45, 1255-1263)
Carduusynes – New polyacetylenic lipids isolated from a marine sponge, Phakellia carduus, collected during scientific trawling operations (below 350 m) in the Great Australian Bight.
(Aust J Chem, 1994, 47, 1901-1918)
Hippospongins – New furanoterpenes isolated from a marine sponge, Hippospongia sp., collected during scientific trawling operations in the Great Australian Bight.
(J Nat Prod, 1996, 59, 1024-1028)
Dictyosphaerin – A novel bicyclic "prostaglandin-like" lipid isolated from a rare marine green alga, Dictyosphaerea sericea, collected of intertidal rock platforms along the southern coast of Australia.
(J Nat Prod, 1996, 59, 1154-1156)
Sigmosceptrellins – A rare class of sponge norterpene endoperoxides isolated from a Great Australian Bight marine sponge, Sigmosceptrella sp. Sigmosceptrellin D and E were the first examples of this structure class to possess a hydroperoxy moiety, a discovery that prompted the proposal of a plausible biosynthetic origin for the endoperoxy moiety, involving an intramolecular Michael Addition. This biosynthetic pathway has since been widely endorsed, and has been the basis for the first successful biomimetic synthesis into this structure class.
(J Nat Prod, 1999, 62, 214-218)
Dragmacidins – New alkaloids from a sponge, Spongosorities sp, collected during scientific trawling operations of the coast of South Australia. In addition to existing as equilibrating tautomers, these unique heterocyclic scaffolds possessed significant inhibitory activity against target serine-threonine protein phosphatases.
For further commentary on Australian marine biodiscovery read the following;
Marine Bioprospecting: Trawling for treasure and pleasure
Natural products and pharmacognosy research in Australasia
Marine natural products chemistry: Past, present, and future
(Aust J Chem, 2010, 63, 851-854)
Biologically active natural products from Australian marine organisms