Category:PK

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* an acyltransferase ('''AT'''), and
 
* an acyltransferase ('''AT'''), and
 
* an acyl carrier protein ('''ACP''').
 
* an acyl carrier protein ('''ACP''').
−
 
−
After elongation, β-ketone is reduced.  In fatty acid biosynthesis, the chain is fully reduced by the following three steps:
 
−
* 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''').
 
−
In polyketide synthase, the reduction is patial.
 
−
 
−
Finally, the chain is terminated by a thioesterase ('''TE''') activity and
 
−
allows Claisen cyclization ('''CYC'''). 
 
 
|
 
|
−
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。
+
ポリケチドは脂肪酸の合成に同じく、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。よく使われる初期ユニットはアセチルCoAやプロピオニルCoAで、それらをマロニルCoAやメチルマロニルCoAで伸張していきます。
 
鎖の伸長に使う反応は
 
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
 
* β-ケトアシル合成酵素 ('''KS''') によるクライゼン縮合
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* アシル輸送タンパク質 ('''ACP''')  
 
* アシル輸送タンパク質 ('''ACP''')  
 
です。
 
です。
 +
}}
  
−
また、伸張後に重要な反応は
+
{{Twocolumn|
 +
After elongation, β-ketone is reduced.  In fatty acid biosynthesis, the chain is fully reduced by the following three steps:
 +
* 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''').
 +
In polyketide synthase, the reduction is patial.
 +
|
 +
伸張の後に、ケト基を還元します。完全に還元して酸素を除くと脂肪酸になりますが、ポリケチドの多くは還元が部分的にストップします。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
 
* 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
 
* 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
 
*  エノイル還元酵素 ('''ER''') による二重結合の還元
 
です。
 
です。
 +
}}
  
 +
{{Twocolumn|
 +
Finally, the chain is terminated by a thioesterase ('''TE''') activity and
 +
allows Claisen cyclization ('''CYC'''). 
 +
|
 
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。
 
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。
 
}}
 
}}
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{| class="wikitable"
 
{| class="wikitable"
−
!colspan="4"| Linear Chain and Related ()
+
!colspan="3" style="background:lightgray"| Linear Chain and Related (L)
 
|-
 
|-
 
|  
 
|  
−
{| class="collapsible collapsed" style="width:150px"
+
{| class="collapsible collapsed" style="width:200px"
 
! Straight (LS)
 
! Straight (LS)
 
|-
 
|-
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|}
 
|}
 
|  
 
|  
−
{| class="collapsible collapsed" style="width:150px"
+
{| class="collapsible collapsed" style="width:200px"
 
! Polyether (LE)
 
! Polyether (LE)
 
|-
 
|-
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|
 
|
 
|-  
 
|-  
−
!colspan="4"| Aromatic and Diels-Alder Related (most often by iterative type II)
+
!colspan="3" style="background:lightgray"| Aromatic and Diels-Alder Related (most often by iterative type II)
 
|-
 
|-
 
|  
 
|  
−
{| class="collapsible collapsed" style="width:150px"
+
{| class="collapsible collapsed" style="width:200px"
 
! Monocyclic (A1)
 
! Monocyclic (A1)
 
|-
 
|-
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|}
 
|}
 
|  
 
|  
−
{| class="collapsible collapsed"  
+
{| class="collapsible collapsed" style="width:200px"
 
! Bicyclic (A2)
 
! Bicyclic (A2)
 
|-
 
|-
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|}
 
|}
 
|  
 
|  
−
{| class="collapsible collapsed"  
+
{| class="collapsible collapsed" style="width:200px"
 
! Tricyclic (A3)
 
! Tricyclic (A3)
 
|-
 
|-
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| hypericin
 
| hypericin
 
|}
 
|}
 +
|-
 
|
 
|
−
{| class="collapsible collapsed" style="width:150px"
+
{| class="collapsible collapsed" style="width:200px"
 
! Tetracyclic (A4)
 
! Tetracyclic (A4)
 
|-
 
|-
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| Angucycline
 
| Angucycline
 
|}
 
|}
 +
|
 +
{| class="collapsible collapsed" style="width:200px"
 +
! Others (AO)
 
|-
 
|-
−
!colspan="4"| Macrolides (most often by non-iterative type I)
+
| ?
−
|-
+
−
|style="width:150px"|
+
−
{| class="collapsible collapsed" style="width:150px"
+
−
! Polyene (MN)
+
−
|-
+
−
| Manumycin
+
−
|-
+
−
| Nystatin
+
−
|-
+
−
| Amphotericin
+
 
|}
 
|}
−
|style="width:150px"|
 
−
{| class="collapsible collapsed" style="width:150px"
 
−
! Cyclic Imines (MI)
 
 
|-
 
|-
−
| Spirolide
+
!colspan="3" style="background:lightgray"| Macrolides (most often by non-iterative type I)
−
|-
+
−
| Pinnatoxin
+
−
|}
+
−
|style="width:150px"|
+
−
{| class="collapsible collapsed" style="width:150px"
+
−
! Ansamacrolide (MA)
+
−
|-
+
−
| Rifamycin
+
−
|-
+
−
| Ansamycin
+
−
|}
+
−
|style="width:150px"|
+
−
{| class="collapsible collapsed" style="width:150px"
+
−
! Polyether (ME)
+
−
|-
+
−
| Nonactin, Nactin
+
−
|}
+
 
|-
 
|-
−
|style="width:150px"|
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|style="width:200px"|
−
{| class="collapsible collapsed" style="width:150px"
+
{| class="collapsible collapsed" style="width:200px"
 
! 12-membered (M2)
 
! 12-membered (M2)
 
|-
 
|-
 
|
 
|
 
|}
 
|}
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|style="width:150px"|
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|style="width:200px"|
−
{| class="collapsible collapsed" style="width:150px"
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{| class="collapsible collapsed" style="width:200px"
 
! 14-membered (M4)
 
! 14-membered (M4)
 
|-
 
|-
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| Zearalenone
 
| Zearalenone
 
|}
 
|}
−
|style="width:150px"|
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|style="width:200px"|
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{| class="collapsible collapsed" style="width:150px"
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{| class="collapsible collapsed" style="width:200px"
 
! 16-membered (M6)
 
! 16-membered (M6)
 
|-
 
|-
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| Tylosin
 
| Tylosin
 
|}
 
|}
−
|style="width:150px"|
+
|-
−
{| class="collapsible collapsed" style="width:150px"
+
|style="width:200px"|
−
! More (MM)
+
{| class="collapsible collapsed" style="width:200px"
 +
! Polyene (MN)
 +
|-
 +
| Manumycin
 +
|-
 +
| Nystatin
 +
|-
 +
| Amphotericin
 +
|}
 +
|style="width:200px"|
 +
{| class="collapsible collapsed" style="width:200px"
 +
! Polyether (ME)
 +
|-
 +
| Nonactin, Nactin
 +
|}
 +
|style="width:200px"|
 +
{| class="collapsible collapsed" style="width:200px"
 +
! Cyclic Imines (MI)
 +
|-
 +
| Spirolide
 +
|-
 +
| Pinnatoxin
 +
|}
 +
|-
 +
|style="width:200px"|
 +
{| class="collapsible collapsed" style="width:200px"
 +
! Ansamacrolide (MA)
 +
|-
 +
| Rifamycin
 +
|-
 +
| Ansamycin
 +
|}
 +
|style="width:200px"|
 +
{| class="collapsible collapsed" style="width:200px"
 +
! Others (MO)
 
|-
 
|-
 
| Bryostatin (26)<ref>It 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>
 
| Bryostatin (26)<ref>It 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>

Revision as of 18:09, 18 December 2010

Polyketide (ポリケチド)

Contents

Class Overview

Polyketides are synthesized through the polymerization of acetyl units (β-ketomethylene) as in fatty acid biosynthesis. Typical starter units are short-chain fatty acids (e.g. acetyl-CoA or propionyl-CoA), on to which extender units (e.g. malonyl-CoA or methylmalonyl-CoA) are repeatedly polymerized. The key reactions for the chain extension are:

  • Claisen condensation by β-ketoacyl synthase (KS)
  • an acyltransferase (AT), and
  • an acyl carrier protein (ACP).

After elongation, β-ketone is reduced. In fatty acid biosynthesis, the chain is fully reduced by the following three steps:

  • 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).
In polyketide synthase, the reduction is patial.

Finally, the chain is terminated by a thioesterase (TE) activity and allows Claisen cyclization (CYC).

Table 1. Polyketide Classification
1st Class
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
griseofulvin, rubrofusarin, emodin, alizarin, pachybasin, xanthone, versicolorin A, aflatoxin B1, sterigmatocystin, tajixanthone

PK9: Nine C2 Units

Tetracyclines
terramycin, aureomycin, daunomycin


Linear Chain and Related (L)
Acetogenins (LA)
Aromatic and Diels-Alder Related (most often by iterative type II)
Macrolides (most often by non-iterative type I)

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)



Cite error: <ref> tags exist, but no <references/> tag was found

Subcategories

This category has only the following subcategory.

P

  • [×] PKS‎ (empty)
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