Category:PK
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==Class Overview== | ==Class Overview== | ||
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+ | |||
+ | <!----Antimycin | ||
+ | Elfamycin | ||
+ | Kijanimicin | ||
+ | Sorbicillin polymers | ||
+ | ----> | ||
+ | |||
+ | {{Twocolumn| | ||
+ | Polyketides are synthesized through the polymerization of acetyl units (β-ketomethylene chain). | ||
+ | The key reactions for chain extensions are: | ||
+ | * Claisen condensation by β-ketoacyl synthase ('''KS''') | ||
+ | * an acyltransferase ('''AT'''), and | ||
+ | * an acyl carrier protein ('''ACP'''). | ||
+ | After elongation, key reactions in synthesis are: | ||
+ | * reduction to an alcohol by ketoreductase ('''KR'''), | ||
+ | * dehydration to the conjugated ester by dehydratase ('''DH'''), and | ||
+ | * reduction of the double bond by enoyl reductase ('''ER'''). | ||
+ | Finally, the chain is terminated by a thioesterase ('''TE''') activity and | ||
+ | allows cyclization (lactonization). | ||
+ | | | ||
+ | ポリケチドはアセチル単位 (β-ケトメチレン鎖) の重合によって作られます。 | ||
+ | 鎖の伸長に使う反応は | ||
+ | * β-ケトアシル合成酵素 ('''KS''') によるクライゼン縮合 | ||
+ | * アシル基転移酵素 ('''AT''') による伸長と、それを支える | ||
+ | * アシル輸送タンパク質 ('''ACP''') | ||
+ | です。また、伸張後に重要な反応は | ||
+ | * ケト還元酵素 ('''KR''') によるアルコールへの還元 | ||
+ | * 脱水酵素 ('''DH''') による共役エステルからの脱水 | ||
+ | * エノイル還元酵素 ('''ER''') による二重結合の還元 | ||
+ | です。最後に、チオエステル分解酵素 ('''TE''') によって伸張が止まり、ラクトン化 (閉環) します。 | ||
+ | }} | ||
+ | |||
+ | {| class="wikitable" | ||
+ | !colspan="3" align="center"| Extent of Reduction | ||
+ | |- | ||
+ | | ''fully reduced'' || ''partially reduced'' || ''unreduced'' | ||
+ | |- | ||
+ | | fatty acids, linear PKs || macrolides || aromatics | ||
+ | |} | ||
+ | |||
+ | {| class="wikitable" | ||
+ | !colspan="4"| Linear Chain and Related | ||
+ | |- | ||
+ | | Linear polyketides | ||
+ | | Polyether polyketides | ||
+ | | Acetogenins | ||
+ | | Cyclic imines | ||
+ | |- | ||
+ | <!---chain 2nd class---> | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | linear | ||
+ | |} | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | nigericin | ||
+ | |- | ||
+ | | monensin | ||
+ | |} | ||
+ | | | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | Spirolide | ||
+ | |- | ||
+ | | Pinnatoxin | ||
+ | |} | ||
+ | |- | ||
+ | !colspan="4"| Aromatic and Related | ||
+ | |- | ||
+ | | with Benzene <br/> orsellinic acid, benzophenone, altenariol | ||
+ | | with Naphthalene <br/> statins | ||
+ | | with Anthracene <br/> | ||
+ | | Tetracyclines <br/> | ||
+ | |- | ||
+ | <!---aromatic 2nd class---> | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | salicylic acid | ||
+ | |} | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | lovastatin | ||
+ | |- | ||
+ | | aflatoxins | ||
+ | |} | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | emodin | ||
+ | |- | ||
+ | | sennoside | ||
+ | |- | ||
+ | | hypericin | ||
+ | |} | ||
+ | | | ||
+ | {| class="collapsible collapsed" | ||
+ | | Linear tetracyclines | ||
+ | |- | ||
+ | | Angucycline | ||
+ | |} | ||
+ | |- | ||
+ | !colspan="4"| Macrolides (most often by non-iterative type I) | ||
+ | |- | ||
+ | | Polyene Type | ||
+ | * Manumycin | ||
+ | * Nystatin | ||
+ | * Amphotericin | ||
+ | | Macrolides | ||
+ | * Ansamycin | ||
+ | * Avermectin (16-membered), Milbemycin (20-membered) | ||
+ | * Bafilomycin (16-membered) | ||
+ | * Bryostatin (26-membered. lacks AT domain as in mupirocin, leinamycin<ref>Nguyen T, Ishida K, Jenke-Kodama H, Dittmann E, Gurgui C, Hochmuth T, Taudien S, Platzer M, Hertweck C, Piel J (2008) "Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection" ''Nat Biotechnol'' 26:225 - 233 PMID 18223641</ref>) | ||
+ | * Colletodiol (14-membered) | ||
+ | * Cytovaricin | ||
+ | * Erythromycin (14-membered) 6-deoxy sugars (L-cladinose and D-desosamine) are attached. | ||
+ | * Fluvirucin (14-membered) | ||
+ | * Myxovirescin (28-membered http://www.indiana.edu/~drwchem/pdfs/50.pdf) | ||
+ | * Nonactin, Nactin | ||
+ | * Natamycin (26-membered =Pimaricin) | ||
+ | * Oligomycin (16-membered) | ||
+ | * Tacrolimus (23-membered =FK-506 or Fujimycin) | ||
+ | * Tylosin (16-memberd) | ||
+ | | | ||
+ | |} | ||
==Polyketide Synthase (PKS) == | ==Polyketide Synthase (PKS) == | ||
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| PKS-NRPS hybrid type | | PKS-NRPS hybrid type | ||
Curacin A (Lyngbya), Shiphonazole (Herpetosiphon), Jamaicamide A (Lyngbya), Cylindrospermopsin (Cylindrospermopsis) | Curacin A (Lyngbya), Shiphonazole (Herpetosiphon), Jamaicamide A (Lyngbya), Cylindrospermopsin (Cylindrospermopsis) | ||
− | |||
|} | |} | ||
− | {| | + | |
+ | {| class="collapsible collapsed" | ||
|- | |- | ||
| [[MOL:1,3,8-Trihydroxyaceto-Naphthalene.Mol|1,3,8-Trihydroxyaceto-Naphthalene]] | | [[MOL:1,3,8-Trihydroxyaceto-Naphthalene.Mol|1,3,8-Trihydroxyaceto-Naphthalene]] |
Revision as of 09:03, 16 December 2010
Polyketide (ポリケチド)
Contents |
Class Overview
1st Class | ||
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PK4: Four C2 Units orsellinic acid, 6-methylsalicylic acid, triacetic acid lactone, asperlin, usnic acid, methylphloracetophenone, penicillic acid, patulin |
PK5: Five C2 Units citrinin, aflatoxin, augenone, sepedonin, stipitatonic acid |
PK6: Six C2 Units plumbagin, 7-methyljuglone, juglone, variotin |
PK7: Seven and eight C2 Units Anthraquinone rings |
PK9: Nine C2 Units Tetracyclines | |
Polyketides are synthesized through the polymerization of acetyl units (β-ketomethylene chain). The key reactions for chain extensions are:
- Claisen condensation by β-ketoacyl synthase (KS)
- an acyltransferase (AT), and
- an acyl carrier protein (ACP).
- reduction to an alcohol by ketoreductase (KR),
- dehydration to the conjugated ester by dehydratase (DH), and
- reduction of the double bond by enoyl reductase (ER).
Extent of Reduction | ||
---|---|---|
fully reduced | partially reduced | unreduced |
fatty acids, linear PKs | macrolides | aromatics |
Linear Chain and Related | |||||||||||
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Linear polyketides | Polyether polyketides | Acetogenins | Cyclic imines | ||||||||
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Aromatic and Related | |||||||||||
with Benzene orsellinic acid, benzophenone, altenariol |
with Naphthalene statins |
with Anthracene |
Tetracyclines | ||||||||
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Macrolides (most often by non-iterative type I) | |||||||||||
Polyene Type
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Macrolides
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Polyketide Synthase (PKS)
species | Actinomycetes | Cyanobacteria | γ-Proteobacteria | Fungi | Dinoflagellates |
---|---|---|---|---|---|
Type-I PKS | Ο | Ο | Ο | Χ | Ο |
Type-II PKS | Ο | Χ | Χ | Ο | Χ |
NRPS | Ο | Ο | Ο | Ο | Χ |
deoxysugar | Ο | Χ | Χ | Χ | Χ |
Terpene | Δ | Χ | Χ | Ο | Χ |
Type I PKS (non-iterative)
- Multi catalytic domains exist in a single protein
- Chain length is determined by the number of catalytic domains.
- Products are non-aromatic and have larger masses.
Ref. Erythromycin biosynthesis in Nat Prod Rep 18, 380 (2001)
Type II PKS (iterative)
- Three proteins (KSα, KSβ, ACP) are repeatedly used for carbon chain elongation.
- Chain length is determined by another protein, CLF.
- In bacteria, products are aromatic (e.g. chiorotetracycline, pradimicin).
- In fungi, products are both non-aromatic and aromatic.
Non-ribosomal peptide synthase (NRPS)
Coupling with PKS and NRPS
- vancomycin ()
- leinamycin (Curr opin chem biol 7:285, 2003)
- pseurotin (chem bio chem 8:1736-1743, 2007)
- curacin (curr opin chem biol 13:216, 2009)
- epothilone
- rapamycin
PKS in Fungi
- both aromatic and non-aromatic compounds are generated by iterative PKS
- methyl branch is transferred from methionine, not methylmalonyl CoA
Ref. Dewick, PM Medicinal Natural Products (2009)
Decoration
deoxysugars
deoxygenation, c-methylation, amination, n-methylation, ketosugar,
Unusual structures
Phoma | zaragozic acid, phomoidoride | Streptomyces | yatakemycin, leinamycin, saframycin, neocarzinostatin, staurosporin, FR182877 | Other bacteria | PKS-NRPS hybrid type
Curacin A (Lyngbya), Shiphonazole (Herpetosiphon), Jamaicamide A (Lyngbya), Cylindrospermopsin (Cylindrospermopsis) |
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