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Ian Paterson - One of the best experts on this subject based on the ideXlab platform.
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Actin‐Binding MArine MAcrolides: TotAl Synthesis And BiologicAl ImportAnce
Angewandte Chemie International Edition, 2002Co-Authors: Kap-sun Yeung, Ian PatersonAbstract:MArine orgAnisms produce A fAscinAting rAnge of structurAlly diverse secondAry metAbolites, which often possess unusuAl And sometimes unexpected biologicAl Activities. This structurAl diversity mAkes these mArine nAturAl products excellent moleculAr probes for the investigAtion of biochemicAl pAthwAys. Recently, A number of novel And stereochemicAlly complex mAcrolides, hAving A lArge mAcrolActone (22- to 44-membered) ring, thAt interAct with the Actin cycloskeleton hAve been isolAted from different mArine sources. Actin, like tubulin, is A mAjor component of the cytoskeleton And hAs importAnt cellulAr functions. Although the detAils of these interActions Are still under investigAtion, these mArine mAcrolides Are becoming increAsingly importAnt As novel moleculAr probes to help elucidAte the cellulAr functions of Actin. Owing to their potent Antitumor Activities, these compounds, for exAmple the Aplyronines, Also hAve potentiAl for preclinicAl development in cAncer chemotherApy. Their AppeAling moleculAr structures, with An AbundAnce of stereochemistry, And biologicAl significAnce, coupled with the extremely limited AvAilAbility from the mArine sources, hAve stimulAted enormous interest in the synthesis of these compounds. This review summArizes the biologicAl properties of these unusuAl mArine nAturAl products And feAtures the recently completed totAl syntheses of Swinholide A, scytophycin C, Aplyronine A, mycAlolide A--All of these being potent cytotoxic Agents thAt tArget Actin--And A diAstereoisomer of ulApuAlide A. RAther thAn detAiling eAch individuAl step of these multistep totAl syntheses, the different synthetic strAtegies, key reActions, And methods Adopted for controlling the stereochemistry Are compAred.
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OrgAnic ReActions - Asymmetric Aldol ReActions Using Boron EnolAtes
Organic Reactions, 1997Co-Authors: C. J. Cowden, Ian PatersonAbstract:The directed Aldol reAction Allows the construction of new cArbon–cArbon bonds in A regio-, diAstereo-, And enAntioselective mAnner. The kineticAlly controlled, boron-mediAted Aldol reAction is pArticulArly powerful for the efficient synthesis of β-hydroxy cArbonyl compounds. CompAred to other metAl enolAtes, the boron–oxygen bond in boron enolAtes is relAtively short which, on Addition to Aldehydes, leAds to tight cyclic trAnsition stAtes And highly stereoselective cArbon–cArbon bond formAtion. Moreover, vAriAtion of the steric demAnds of the ligAnds on boron Allows discriminAtion between competing trAnsition stAtes. ChirAl AuxiliAries AttAched to the boron enolAte Are frequently employed to control the relAtive And Absolute stereochemistry of the Aldol products. Asymmetric reActions using chirAl ligAnds on boron Are Also possible And these produce useful enAntiomericAlly enriched Adducts. The utility of boron-mediAted Aldol reActions hAs been demonstrAted in numerous totAl syntheses of complex polyoxygenAted nAturAl products, And severAl of these Are highlighted in the ApplicAtion to Synthesis section of this chApter. SeverAl reviews of the directed Aldol reAction Are AvAilAble, including the OrgAnic ReActions chApter by MukAiyAmA in 1981.9 The mAteriAl covered in this review concerns only the Asymmetric formAtion of β-hydroxy cArbonyl compounds using boron enolAtes And surveys the literAture from 1981 until the end of 1995. Keywords: Asymmetric Aldol reActions; mechAnism; stereochemistry; stereocontrol; enolizAtion selectivity; π fAciAl selectivity; scope; limitAtions; chirAl Aldehydes; Asymmetric induction; enolAte geometry; betA Alkoxy Aldehydes; AuxiliAry mediAted reActions; substrAte mediAted reActions; chirAl ketones; Alkoxy chirAl ketones; ligAnd mediAted reActions; chirAl boron reAgents; triple Asymmetric induction; synthesis; cytovAricin; mAcbein 1; FK-506; discodermolide; ACRL toxin IIIB; elAiophylin; denticulAtion A/B; ebelActone A/B; Swinholide A; compArison of methods; experimentAl conditions; experimentAl procedures; tAbulAr survey
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the totAl synthesis of Swinholide A pArt 3 A stereocontrolled synthesis of pre Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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The totAl synthesis of Swinholide A. PArt 4: Synthesis of Swinholide A And isoSwinholide A from the protected monomeric seco Acid, pre-Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, Julian D. Smith, Richard A. Ward, Kap-sun Yeung, John G. Cuimming, Serge LamboleyAbstract:AbstrAct Swinholide A And isoSwinholide A were synthesised in 7 steps from the fully protected seco Acid 4 . Key steps include: ( i) bimoleculAr AcylAtion, 7 + 10 → 12 , ( ii ) selective hydrolysis of the methyl ester, 16 → 17 , And ( iii ) regioselective mAcrolActonisAtion. 17 → 18 . The monomeric lActone AnAlogues 2 And 5 were prepAred by regioselective mAcrolActonisAtion of the seco Acid 6 , where the ring size wAs controlled by vAriAtion of the reAction conditions.
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The totAl synthesis of Swinholide A. PArt 3: A stereocontrolled synthesis of (−)-pre-Swinholide A.
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
Julian D. Smith - One of the best experts on this subject based on the ideXlab platform.
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the totAl synthesis of Swinholide A pArt 3 A stereocontrolled synthesis of pre Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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The totAl synthesis of Swinholide A. PArt 4: Synthesis of Swinholide A And isoSwinholide A from the protected monomeric seco Acid, pre-Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, Julian D. Smith, Richard A. Ward, Kap-sun Yeung, John G. Cuimming, Serge LamboleyAbstract:AbstrAct Swinholide A And isoSwinholide A were synthesised in 7 steps from the fully protected seco Acid 4 . Key steps include: ( i) bimoleculAr AcylAtion, 7 + 10 → 12 , ( ii ) selective hydrolysis of the methyl ester, 16 → 17 , And ( iii ) regioselective mAcrolActonisAtion. 17 → 18 . The monomeric lActone AnAlogues 2 And 5 were prepAred by regioselective mAcrolActonisAtion of the seco Acid 6 , where the ring size wAs controlled by vAriAtion of the reAction conditions.
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The totAl synthesis of Swinholide A. PArt 3: A stereocontrolled synthesis of (−)-pre-Swinholide A.
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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towArds the synthesis of Swinholide A And scytophycin c A highly stereocontrolled synthesis of pre Swinholide A
Tetrahedron Letters, 1994Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct The fully protected monomeric unit 19 of the mArine mAcrodiolide, Swinholide A (1), wAs obtAined with > 97% ds by A MukAiyAmA Aldol reAction between 16 And 5, followed by A boron-mediAted reduction to give the syn 1,3-diol 18. Deprotection gAve (−)-pre-Swinholide A (2), the putAtive biosynthetic precursor of 1.
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TowArds the synthesis of Swinholide A And scytophycin C. A highly stereocontrolled synthesis of (−)-pre-Swinholide A
Tetrahedron Letters, 1994Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct The fully protected monomeric unit 19 of the mArine mAcrodiolide, Swinholide A (1), wAs obtAined with > 97% ds by A MukAiyAmA Aldol reAction between 16 And 5, followed by A boron-mediAted reduction to give the syn 1,3-diol 18. Deprotection gAve (−)-pre-Swinholide A (2), the putAtive biosynthetic precursor of 1.
Kap-sun Yeung - One of the best experts on this subject based on the ideXlab platform.
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Actin‐Binding MArine MAcrolides: TotAl Synthesis And BiologicAl ImportAnce
Angewandte Chemie International Edition, 2002Co-Authors: Kap-sun Yeung, Ian PatersonAbstract:MArine orgAnisms produce A fAscinAting rAnge of structurAlly diverse secondAry metAbolites, which often possess unusuAl And sometimes unexpected biologicAl Activities. This structurAl diversity mAkes these mArine nAturAl products excellent moleculAr probes for the investigAtion of biochemicAl pAthwAys. Recently, A number of novel And stereochemicAlly complex mAcrolides, hAving A lArge mAcrolActone (22- to 44-membered) ring, thAt interAct with the Actin cycloskeleton hAve been isolAted from different mArine sources. Actin, like tubulin, is A mAjor component of the cytoskeleton And hAs importAnt cellulAr functions. Although the detAils of these interActions Are still under investigAtion, these mArine mAcrolides Are becoming increAsingly importAnt As novel moleculAr probes to help elucidAte the cellulAr functions of Actin. Owing to their potent Antitumor Activities, these compounds, for exAmple the Aplyronines, Also hAve potentiAl for preclinicAl development in cAncer chemotherApy. Their AppeAling moleculAr structures, with An AbundAnce of stereochemistry, And biologicAl significAnce, coupled with the extremely limited AvAilAbility from the mArine sources, hAve stimulAted enormous interest in the synthesis of these compounds. This review summArizes the biologicAl properties of these unusuAl mArine nAturAl products And feAtures the recently completed totAl syntheses of Swinholide A, scytophycin C, Aplyronine A, mycAlolide A--All of these being potent cytotoxic Agents thAt tArget Actin--And A diAstereoisomer of ulApuAlide A. RAther thAn detAiling eAch individuAl step of these multistep totAl syntheses, the different synthetic strAtegies, key reActions, And methods Adopted for controlling the stereochemistry Are compAred.
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the totAl synthesis of Swinholide A pArt 3 A stereocontrolled synthesis of pre Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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The totAl synthesis of Swinholide A. PArt 4: Synthesis of Swinholide A And isoSwinholide A from the protected monomeric seco Acid, pre-Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, Julian D. Smith, Richard A. Ward, Kap-sun Yeung, John G. Cuimming, Serge LamboleyAbstract:AbstrAct Swinholide A And isoSwinholide A were synthesised in 7 steps from the fully protected seco Acid 4 . Key steps include: ( i) bimoleculAr AcylAtion, 7 + 10 → 12 , ( ii ) selective hydrolysis of the methyl ester, 16 → 17 , And ( iii ) regioselective mAcrolActonisAtion. 17 → 18 . The monomeric lActone AnAlogues 2 And 5 were prepAred by regioselective mAcrolActonisAtion of the seco Acid 6 , where the ring size wAs controlled by vAriAtion of the reAction conditions.
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The totAl synthesis of Swinholide A. PArt 3: A stereocontrolled synthesis of (−)-pre-Swinholide A.
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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towArds the synthesis of Swinholide A And scytophycin c A highly stereocontrolled synthesis of pre Swinholide A
Tetrahedron Letters, 1994Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct The fully protected monomeric unit 19 of the mArine mAcrodiolide, Swinholide A (1), wAs obtAined with > 97% ds by A MukAiyAmA Aldol reAction between 16 And 5, followed by A boron-mediAted reduction to give the syn 1,3-diol 18. Deprotection gAve (−)-pre-Swinholide A (2), the putAtive biosynthetic precursor of 1.
John G. Cumming - One of the best experts on this subject based on the ideXlab platform.
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the totAl synthesis of Swinholide A pArt 3 A stereocontrolled synthesis of pre Swinholide A
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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The totAl synthesis of Swinholide A. PArt 3: A stereocontrolled synthesis of (−)-pre-Swinholide A.
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct Two coupling strAtegies for (−)-pre-Swinholide A were devised bAsed on the AnAlysis in Scheme 1. In the first route, A boron-mediAted Aldol reAction between the ethyl ketone 19 And the Aldehyde 3 wAs used to construct the C15-C16 bond with moderAte diAstereoselectivity. In the second route, A MukAiyAmA Aldol reAction between the methyl ketone 54 And the Aldehyde 4 introduced the C18-C19 bond with complete stereocontrol.
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The totAl synthesis of Swinholide A. PArt 1: A stereocontrolled synthesis of A C19-C32 segment
Tetrahedron, 1995Co-Authors: Ian Paterson, John G. Cumming, Richard A. Ward, Serge LamboleyAbstract:AbstrAct The C 19 -C 32 segment 10 of Swinholide A wAs prepAred in 15 steps (8% yield, 82% ds) from (±)- 16 . Key steps include ( i ) the ShArpless epoxidAtion, 16 → 17 , ( ii ) the AcetAl AllylAtion, 15 → 23 , ( iii ) the Anti Aldol Addition, 13 + 14 → 12 , And ( iv ) the Alkene hydroborAtion, 30 → 31 . The Swinholides Are A series of complex polyketide mAcrodiolides, which displAy potent cytotoxicity AgAinst A vAriety of humAn tumour cell lines. 1,2 Swinholide A, isolAted from the mArine sponge TheonellA swinhoei , wAs first reported As An AntifungAl Agent by CArmely And KAshmAn in 1985.1 Using NMR methods And chemicAl
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towArds the synthesis of Swinholide A And scytophycin c A highly stereocontrolled synthesis of pre Swinholide A
Tetrahedron Letters, 1994Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct The fully protected monomeric unit 19 of the mArine mAcrodiolide, Swinholide A (1), wAs obtAined with > 97% ds by A MukAiyAmA Aldol reAction between 16 And 5, followed by A boron-mediAted reduction to give the syn 1,3-diol 18. Deprotection gAve (−)-pre-Swinholide A (2), the putAtive biosynthetic precursor of 1.
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TowArds the synthesis of Swinholide A And scytophycin C. A highly stereocontrolled synthesis of (−)-pre-Swinholide A
Tetrahedron Letters, 1994Co-Authors: Ian Paterson, John G. Cumming, Julian D. Smith, Richard A. Ward, Kap-sun YeungAbstract:AbstrAct The fully protected monomeric unit 19 of the mArine mAcrodiolide, Swinholide A (1), wAs obtAined with > 97% ds by A MukAiyAmA Aldol reAction between 16 And 5, followed by A boron-mediAted reduction to give the syn 1,3-diol 18. Deprotection gAve (−)-pre-Swinholide A (2), the putAtive biosynthetic precursor of 1.
Sivonen Kaarina - One of the best experts on this subject based on the ideXlab platform.
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The Swinholide Biosynthesis Gene Cluster from A TerrestriAl CyAnobActerium, Nostoc sp. StrAin UHCC 0450
'American Society for Microbiology', 2018Co-Authors: Humisto, Anu Karoliina, Liu Liwei, Wang Hao, Machado, João Paulo, Antunes Agostinho, Jokela, Jouni Kalevi, Wahlsten, Matti Per-vilhelm, Permi, Perttu Esko Ilari, Fewer, David Peter, Sivonen KaarinaAbstract:Swinholides Are 42-cArbon ring polyketides with A 2-fold Axis of symmetry. They Are potent cytotoxins thAt disrupt the Actin cytoskeleton. Swinholides were discovered from the mArine sponge TheonellA sp. And were long suspected to be produced by symbiotic bActeriA. MisAkinolide, A structurAl vAriAnt of Swinholide, wAs recently demonstrAted to be the product of A symbiotic heterotrophic proteobActerium. Here, we report the production of Swinholide A by An Axenic strAin of the terrestriAl cyAnobActerium Nostoc sp. strAin UHCC 0450. We locAted the 85-kb trAns-AT polyketide synthAse (PKS) Swinholide biosynthesis gene cluster from A drAft genome of Nostoc sp. UHCC 0450. The Swinholide And misAkinolide biosynthesis gene clusters shAre An Almost identicAl order of cAtAlytic domAins, with 85% nucleotide sequence identity, And they group together in phylogenetic AnAlysis. Our results resolve speculAtion Around the true producer of Swinholides And demonstrAte thAt bActeriA belonging to two distAntly relAted phylA both produce structurAl vAriAnts of the sAme nAturAl product. In Addition, we described A biosynthesis cluster from AnAbAenA sp. strAin UHCC 0451 for the synthesis of the cytotoxic And AntifungAl scytophycin. All of these biosynthesis gene clusters were closely relAted to eAch other And creAted A group of cytotoxic mAcrolide compounds produced by trAns-AT PKSs of cyAnobActeriA And proteobActeriA. IMPORTANCE MAny of the drugs in use todAy originAte from nAturAl products. New cAndidAte compounds for drug development Are needed due to increAsed drug resistAnce. An increAsed knowledge of the biosynthesis of bioActive compounds cAn be used to Aid chemicAl synthesis to produce novel drugs. Here, we show thAt A terrestriAl Axenic culture of Nostoc cyAnobActerium produces Swinholides, which hAve been previously found only from mArine sponge or sAmples relAted to them. Swinholides Are polyketides with A 2-fold Axis of symmetry, And they Are potent cytotoxins thAt disrupt the Actin cytoskeleton. We describe the biosynthesis gene clusters of Swinholide from Nostoc cyAnobActeriA, As well As the relAted cytotoxic And AntifungAl scytophycin from AnAbAenA cyAnobActeriA, And we study the evolution of their trAns-AT polyketide synthAses. Interestingly, Swinholide is closely relAted to misAkinolide produced by A symbiotic heterotrophic proteobActerium, demonstrAting thAt bActeriA belonging to two distAntly relAted phylA And different hAbitAts cAn produce similAr nAturAl products.Peer reviewe
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The Swinholide biosynthetic gene cluster from A terrestriAl cyAnobActerium Nostoc sp. UHCC 0450
'American Society for Microbiology', 2018Co-Authors: Humisto Anu, Jokela Jouni, Liu Liwei, Wahlsten Matti, Wang Hao, Permi Perttu, Machado, João Paulo, Antunes Agostinho, Fewer, David P., Sivonen KaarinaAbstract:Swinholides Are 42-cArbon ring polyketides with A 2-fold Axis of symmetry. They Are potent cytotoxins thAt disrupt the Actin cytoskeleton. Swinholides were discovered from the mArine sponge TheonellA sp. And were long suspected to be produced by symbiotic bActeriA. MisAkinolide, A structurAl vAriAnt of Swinholide, wAs recently demonstrAted to be the product of A symbiotic heterotrophic proteobActerium. Here, we report the production of Swinholide A by An Axenic strAin of the terrestriAl cyAnobActerium Nostoc sp. strAin UHCC 0450. We locAted the 85-kb trAns-AT polyketide synthAse (PKS) Swinholide biosynthesis gene cluster from A drAft genome of Nostoc sp. UHCC 0450. The Swinholide And misAkinolide biosynthesis gene clusters shAre An Almost identicAl order of cAtAlytic domAins, with 85% nucleotide sequence identity, And they group together in phylogenetic AnAlysis. Our results resolve speculAtion Around the true producer of Swinholides And demonstrAte thAt bActeriA belonging to two distAntly relAted phylA both produce structurAl vAriAnts of the sAme nAturAl product. In Addition, we described A biosynthesis cluster from AnAbAenA sp. strAin UHCC 0451 for the synthesis of the cytotoxic And AntifungAl scytophycin. All of these biosynthesis gene clusters were closely relAted to eAch other And creAted A group of cytotoxic mAcrolide compounds produced by trAns-AT PKSs of cyAnobActeriA And proteobActeriA. IMPORTANCE MAny of the drugs in use todAy originAte from nAturAl products. New cAndidAte compounds for drug development Are needed due to increAsed drug resistAnce. An increAsed knowledge of the biosynthesis of bioActive compounds cAn be used to Aid chemicAl synthesis to produce novel drugs. Here, we show thAt A terrestriAl Axenic culture of Nostoc cyAnobActerium produces Swinholides, which hAve been previously found only from mArine sponge or sAmples relAted to them. Swinholides Are polyketides with A 2-fold Axis of symmetry, And they Are potent cytotoxins thAt disrupt the Actin cytoskeleton. We describe the biosynthesis gene clusters of Swinholide from Nostoc cyAnobActeriA, As well As the relAted cytotoxic And AntifungAl scytophycin from AnAbAenA cyAnobActeriA, And we study the evolution of their trAns-AT polyketide synthAses. Interestingly, Swinholide is closely relAted to misAkinolide produced by A symbiotic heterotrophic proteobActerium, demonstrAting thAt bActeriA belonging to two distAntly relAted phylA And different hAbitAts cAn produce similAr nAturAl products.peerReviewe
