[ Pobierz całość w formacie PDF ]
.Cholesterol issynthesized de novo and is also made from phytosterols.It is suggested thatO OHOHO424343, R = H45, R = OH 144 Bioactive Marine Natural Productspossibly all molluscs originally had the capacity to synthesise sterols, butlost this capacity in favour of the energetically less demanding dealkylationof phytosterols.Limpets, such as P.vulgata would, therefore, represent anintermediate evolutionary stage.8.Cholesterol BiosynthesisCholesterol, once believed to be a typical animal sterol, is now one of themost widely distributed sterols in both terrestrial and marine plants andanimals,37 where it is biosynthesised from squalene.Several of the individualenzymes of the early steps of squalene biosynthesis have been isolated.Thebiosynthetic status of cholesterol has been reviewed.149 Insects have no capacityfor de novo sterol synthesis.They rely exclusively on exogenous sources,that is phytosterols.Sterols metabolism in insect has been discussed byIkekawa et al.150 Cholesterol in insects is formed by dealkylation ofphytosterols.The analogous deakylation of sterols also occurs in sponges151and crustaceans.1529.Biosynthesis of Arsenic-Containing CompoundsArsenic containing compounds have been isolated from a number ofmacroalgae,153,154 particularly brown algae, where arsenic occurs at levels of110-40 mg/kg.Arsenic containing ribosides have been identified in somebivalve molluscs.155 It is believed that unicellular algae, which are consumedby the molluscs, are the source of these compounds.The kidney of the giantclam, Tridacna maxima,156,157 had yielded the unusual ribosides.Theother compounds that have been isolated recently are characterised as: N-(52 deoxy-52 -dimethyl-arsinoyl-²-D-ribosyloxyglycine; (2S)-3-(52 -deoxy-52 -dimethylarsinoyl-²-D-ribosyloxy)-2-hydroxypropanoic acid; (2R)-3-(52 -deoxy-52 -dimethyl-arsinoyl-²-D-ribosyloxy)-2-hydroxypropanoic acid; 9-(52 -deoxy-52 -(dimethylarsinoyl)-9H-adenosine; N-[4-(dimethyl-arsinoyl) butanoyltaurineand (2S)-3(52 -deoxy-52 -trimethylarsonio-²-D-ribosyloxy)-2-hydroxypropyl)sulphate.158The arsenic containing compounds are probably formed in marine organismsas follows.The reduction and oxidative methylation of absorbed oceanicarsenate by algae in two stages could give dimethylarsinic acid a knownalgal metabolite.159 The reduction followed by oxidative adenosylation, yieldthe range of dimethylarsinoylribosides that have been identified from algalsources.Adenosylation may precede one or both, of the methylation stages.Trimethylarsonio ribosides (of which the zwitterion (46) is, so far, the onlyknown naturally occurring) may also be formed by this pathway.The stageat which the third methyl group is transferred to arsenic is less certain.It islikely that methylation of arsenic proceeds in algae without adenosylation,thus yielding a tetramethylarsonium salt.Such an arsenic species is yet to beidentified in algae, although it is a common constituent of bivalve molluscsfeeding on unicellular algae.160 Biosynthesis of Bioactive Metabolites of Marine Organisms 145NH2NNONNMe3As OSO3OAsMe2OOOHHO OHHO OH46 47The presence of the nucleoside (47) in Tridacna, as a consequence ofalgal metabolism, supports the proposed pathway for the synthesis of arseniccontaining ribosides by algae.The presence of (46) may represent the firstexample of donation, by S-adenosylmethionine, of all three of its alkyl groupsto a single acceptor (arsenic) within one organism.10.Problems of Microbial ContaminationSeveral metabolites of marine organisms of considerable biological interesthave been obtained in trace quantities.For example, to isolate 100 mg ofbryostatin-2, an antileukaemic agent from the bryozoan Bugularia species,one requires about 1500 kg of the appropriate bryozoan.These metabolitesare probably produced by micro-organisms growing on the surface of theorganism.Conflicting results regarding the chemical constituents and biologicalactivity of different collections of the bryozoan Chartella papyracea havebeen noted.161 The possibilities of microbial contamination are also notexcluded.An autoradiographic study on feeding and transport of metabolitesin the marine bryozoan Membranipora membranaceae has been made byBest and Thorpe.162 The green alga Platymonas convolutae is a symbiont ofthe marine flatworm Convoluta roscoffencis.Tracer experiments with [14-C]labelled precursors have shown that the fatty acids and sterols synthesisedby the alga are provided to the host163 which has the capacity to synthesisecomplex lipids.The biosynthesis of prostaglandins in the tissue homogenatesof fish and other marine invertebrates, such as sea squits and clam, has beencarried out by Ogata et al.164 Several studies on the biosynthesis of waxesters and carotenoids in fish have been reported.Phospholipid biosynthesis in the oyster protozoan parasite, Perkinsusmarinus was studied.165 The biosynthetic gene cluster for antitumorrebeccamycin, a halogenated natural product of the indolocarbazole familywas characterized.166 The cloned genes may help to elucidate the molecularbasis for indolocarbazole biosynthesis and set the stage for the generation ofnovel indolocarbazole analogues by genetic engineering.Current status ofbiosynthesis of pullulan was reviewed.167 146 Bioactive Marine Natural Products11.Concluding RemarksThe biosynthesis of the secondary metabolites of marine algae and marineinvertebrates is fascinating and challenging.In spite of several problemsinvolved in biosynthetic studies, the biosynthetic pathways of several classesof secondary metabolites have been traced using tracer experiments.Biosynthesis of metabolites exhibiting high order of biological activities ortoxicity and produced in minute quantities is still a challenging problem.There is a lot of confusion regarding the origin of compounds of marineorganisms living in symbiotic form or contaminated with bacteria.Feedingexperiments are expected to resolve some of these problems.References1.Bhakuni, D.S.; Jain, S.J.Sci.Ind.Res.1990, 49, 330.2.Fenical, W.; McConnell, D.J.In: Marine Algae in Pharmaceutical Sciences (editedby Y.Tanaka).Walter de Gruter Company, Berlin, 1979.3.Faulkner, D.J.Nat.Prod.Rep.1986, 3, 1.4.Marine Natural Products, Chemical and Biological Perspectives (edited by P.J.Scheuer), 1, 1978.5.Faulkner, D.J.Nat.Prod.Rep.1987, 4, 539.6.Faulkner, D.J.Nat.Prod.Rep.1988, 5, 613.7 [ Pobierz caÅ‚ość w formacie PDF ]
zanotowane.pl doc.pisz.pl pdf.pisz.pl matkasanepid.xlx.pl
.Cholesterol issynthesized de novo and is also made from phytosterols.It is suggested thatO OHOHO424343, R = H45, R = OH 144 Bioactive Marine Natural Productspossibly all molluscs originally had the capacity to synthesise sterols, butlost this capacity in favour of the energetically less demanding dealkylationof phytosterols.Limpets, such as P.vulgata would, therefore, represent anintermediate evolutionary stage.8.Cholesterol BiosynthesisCholesterol, once believed to be a typical animal sterol, is now one of themost widely distributed sterols in both terrestrial and marine plants andanimals,37 where it is biosynthesised from squalene.Several of the individualenzymes of the early steps of squalene biosynthesis have been isolated.Thebiosynthetic status of cholesterol has been reviewed.149 Insects have no capacityfor de novo sterol synthesis.They rely exclusively on exogenous sources,that is phytosterols.Sterols metabolism in insect has been discussed byIkekawa et al.150 Cholesterol in insects is formed by dealkylation ofphytosterols.The analogous deakylation of sterols also occurs in sponges151and crustaceans.1529.Biosynthesis of Arsenic-Containing CompoundsArsenic containing compounds have been isolated from a number ofmacroalgae,153,154 particularly brown algae, where arsenic occurs at levels of110-40 mg/kg.Arsenic containing ribosides have been identified in somebivalve molluscs.155 It is believed that unicellular algae, which are consumedby the molluscs, are the source of these compounds.The kidney of the giantclam, Tridacna maxima,156,157 had yielded the unusual ribosides.Theother compounds that have been isolated recently are characterised as: N-(52 deoxy-52 -dimethyl-arsinoyl-²-D-ribosyloxyglycine; (2S)-3-(52 -deoxy-52 -dimethylarsinoyl-²-D-ribosyloxy)-2-hydroxypropanoic acid; (2R)-3-(52 -deoxy-52 -dimethyl-arsinoyl-²-D-ribosyloxy)-2-hydroxypropanoic acid; 9-(52 -deoxy-52 -(dimethylarsinoyl)-9H-adenosine; N-[4-(dimethyl-arsinoyl) butanoyltaurineand (2S)-3(52 -deoxy-52 -trimethylarsonio-²-D-ribosyloxy)-2-hydroxypropyl)sulphate.158The arsenic containing compounds are probably formed in marine organismsas follows.The reduction and oxidative methylation of absorbed oceanicarsenate by algae in two stages could give dimethylarsinic acid a knownalgal metabolite.159 The reduction followed by oxidative adenosylation, yieldthe range of dimethylarsinoylribosides that have been identified from algalsources.Adenosylation may precede one or both, of the methylation stages.Trimethylarsonio ribosides (of which the zwitterion (46) is, so far, the onlyknown naturally occurring) may also be formed by this pathway.The stageat which the third methyl group is transferred to arsenic is less certain.It islikely that methylation of arsenic proceeds in algae without adenosylation,thus yielding a tetramethylarsonium salt.Such an arsenic species is yet to beidentified in algae, although it is a common constituent of bivalve molluscsfeeding on unicellular algae.160 Biosynthesis of Bioactive Metabolites of Marine Organisms 145NH2NNONNMe3As OSO3OAsMe2OOOHHO OHHO OH46 47The presence of the nucleoside (47) in Tridacna, as a consequence ofalgal metabolism, supports the proposed pathway for the synthesis of arseniccontaining ribosides by algae.The presence of (46) may represent the firstexample of donation, by S-adenosylmethionine, of all three of its alkyl groupsto a single acceptor (arsenic) within one organism.10.Problems of Microbial ContaminationSeveral metabolites of marine organisms of considerable biological interesthave been obtained in trace quantities.For example, to isolate 100 mg ofbryostatin-2, an antileukaemic agent from the bryozoan Bugularia species,one requires about 1500 kg of the appropriate bryozoan.These metabolitesare probably produced by micro-organisms growing on the surface of theorganism.Conflicting results regarding the chemical constituents and biologicalactivity of different collections of the bryozoan Chartella papyracea havebeen noted.161 The possibilities of microbial contamination are also notexcluded.An autoradiographic study on feeding and transport of metabolitesin the marine bryozoan Membranipora membranaceae has been made byBest and Thorpe.162 The green alga Platymonas convolutae is a symbiont ofthe marine flatworm Convoluta roscoffencis.Tracer experiments with [14-C]labelled precursors have shown that the fatty acids and sterols synthesisedby the alga are provided to the host163 which has the capacity to synthesisecomplex lipids.The biosynthesis of prostaglandins in the tissue homogenatesof fish and other marine invertebrates, such as sea squits and clam, has beencarried out by Ogata et al.164 Several studies on the biosynthesis of waxesters and carotenoids in fish have been reported.Phospholipid biosynthesis in the oyster protozoan parasite, Perkinsusmarinus was studied.165 The biosynthetic gene cluster for antitumorrebeccamycin, a halogenated natural product of the indolocarbazole familywas characterized.166 The cloned genes may help to elucidate the molecularbasis for indolocarbazole biosynthesis and set the stage for the generation ofnovel indolocarbazole analogues by genetic engineering.Current status ofbiosynthesis of pullulan was reviewed.167 146 Bioactive Marine Natural Products11.Concluding RemarksThe biosynthesis of the secondary metabolites of marine algae and marineinvertebrates is fascinating and challenging.In spite of several problemsinvolved in biosynthetic studies, the biosynthetic pathways of several classesof secondary metabolites have been traced using tracer experiments.Biosynthesis of metabolites exhibiting high order of biological activities ortoxicity and produced in minute quantities is still a challenging problem.There is a lot of confusion regarding the origin of compounds of marineorganisms living in symbiotic form or contaminated with bacteria.Feedingexperiments are expected to resolve some of these problems.References1.Bhakuni, D.S.; Jain, S.J.Sci.Ind.Res.1990, 49, 330.2.Fenical, W.; McConnell, D.J.In: Marine Algae in Pharmaceutical Sciences (editedby Y.Tanaka).Walter de Gruter Company, Berlin, 1979.3.Faulkner, D.J.Nat.Prod.Rep.1986, 3, 1.4.Marine Natural Products, Chemical and Biological Perspectives (edited by P.J.Scheuer), 1, 1978.5.Faulkner, D.J.Nat.Prod.Rep.1987, 4, 539.6.Faulkner, D.J.Nat.Prod.Rep.1988, 5, 613.7 [ Pobierz caÅ‚ość w formacie PDF ]