Category:TP3

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m (→‎{{Bilingual|Oxidosqualene Cyclase in Eukaryotes|真核生物のオキシドスクアレン環化酵素}})
m (→‎{{Bilingual|バクテリア・シダ類のスクアレン環化酵素|Squalene Cyclase in Bacteria and Ferns}})
 
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==Triterpene (C30)==
 
==Triterpene (C30)==
  
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=={{Bilingual|Ring configuration|環の構造}}==
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=={{Bilingual|環の構造|Ring configuration}}==
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==={{Bilingual|Steroid|ステロイド}}===
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==={{Bilingual|ステロイド|Steroid}}===
 
{{Twocolumn|
 
{{Twocolumn|
 
The basic structure is 4 carbon rings, cyclopenta[a]phenanthrene, gonane, or sterane.
 
The basic structure is 4 carbon rings, cyclopenta[a]phenanthrene, gonane, or sterane.
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</center>
 
</center>
  
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==={{Bilingual|Triterpenes|トリテルペン}}===
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==={{Bilingual|トリテルペン|Triterpenes}}===
  
 
{{Twocolumn|
 
{{Twocolumn|
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}}
 
}}
  
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=={{Bilingual|Biosynthesis|生合成}}==
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=={{Bilingual|生合成|Biosynthesis}}==
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==={{Bilingual|Overview|概要}}===
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==={{Bilingual|概要|Overview}}===
 
{{Twocolumn|
 
{{Twocolumn|
 
The starting point is squalene, which is formed by joining two FPPs tail-to-tail.
 
The starting point is squalene, which is formed by joining two FPPs tail-to-tail.
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{{Twocolumn|
 
{{Twocolumn|
 
* In bacteria, squalene is cyclized via the 17&alpha;-deoxydammarenyl cation to hopene and other triterpenes.
 
* In bacteria, squalene is cyclized via the 17&alpha;-deoxydammarenyl cation to hopene and other triterpenes.
−
* In eukaryotes, 2,3-oxidosqualene is cyclized via the protosteryl cation to lanosterol (animals and fungi), cycloartenol (plants) or parkeol (sea cucumbers) by a series of 1,2-hydride and methyl shifts (Wagner-Meerwein shifts).<ref>In plants, a trace amount of phytosterols comes from lanosterol.<br/>''Ref.'' Ohyama K, Suzuki M, Kikuchi J, Saito K, Muranaka T (2009) Dual biosynthetic pathways to phytosterol via cycloartenol and lanosterol in Arabidopsis ''Proc Natl Acad Sci USA'' 106(3):725-730<br/>Parkeol is also widespread in plants.</ref>
+
* In eukaryotes, 2,3-oxidosqualene is cyclized via the protosteryl cation to lanosterol (animals and fungi), cycloartenol (plants) or parkeol (sea cucumbers) by a series of 1,2-hydride and methyl shifts (Wagner-Meerwein shifts).
 +
* In plants, a trace amount of phytosterols comes from lanosterol <ref>Ohyama K, Suzuki M, Kikuchi J, Saito K, Muranaka T (2009) Dual biosynthetic pathways to phytosterol via cycloartenol and lanosterol in Arabidopsis ''Proc Natl Acad Sci USA'' 106(3):725-730</ref> '''At3g45130''' is lanosterol synthase in ''Arabidopsis'' and its orthologs exist in asterids [[Species:Taraxacum|''Taraxacum officinale'']] and [[Species:Panax|''Panax ginseng]] and eurosid [[Species:Luffa|''Luffa cylindrica]]. Lanosterol synthase exists broadly among eudicots <ref>Kolesnikova MD, Xiong Q, Lodeiro S, Hua L, Matsuda SPT (2006) Lanosterol biosynthesis in plants ''Arch Biochem Biophys'' 447:87-95</ref>. Parkeol is also widespread in plants.
 
* In plants, various triterpenes arise from the 17&beta;-dammarenyl cation.
 
* In plants, various triterpenes arise from the 17&beta;-dammarenyl cation.
 
|
 
|
 
* バクテリアでは、スクアレンが環化して17&alpha;-ダンマラン型カチオンとなり、最終的にホペン等のトリテルペンになります。
 
* バクテリアでは、スクアレンが環化して17&alpha;-ダンマラン型カチオンとなり、最終的にホペン等のトリテルペンになります。
 
* 真核生物では、2,3-オキシドスクアレンが環化してプロトステロール型カチオンを作り、プロトンとメチル基の転移 (Wagner-Meerweinシフト) を経て1,2-ラノステロール (動物や真菌類)、シクロアルテノール (植物)や、パルケオール（ナマコ） になります。
 
* 真核生物では、2,3-オキシドスクアレンが環化してプロトステロール型カチオンを作り、プロトンとメチル基の転移 (Wagner-Meerweinシフト) を経て1,2-ラノステロール (動物や真菌類)、シクロアルテノール (植物)や、パルケオール（ナマコ） になります。
 +
* 植物ではラノステロールからも一部の植物ステロールが合成されます。シロイヌナズナの '''At3g45130''' はラノステロール合成遺伝子であり、オーソログが菊類の [[Species:Taraxacum|''Taraxacum officinale'']] や [[Species:Panax|''Panax ginseng'']]、 真正バラ類の [[Species:Luffa|''Luffa cylindrica'']] にあることから、真正双子葉類に幅広く見られると考えられます。パーケオールも幅広い植物に見られます。
 
* 更に植物の場合、17&beta;-ダンマラン型のカチオンから様々なトリテルペンが生成されます。
 
* 更に植物の場合、17&beta;-ダンマラン型のカチオンから様々なトリテルペンが生成されます。
 
}}
 
}}
  
−
==={{Bilingual|Oxidosqualene Cyclase in Eukaryotes|真核生物のオキシドスクアレン環化酵素}}===
+
;References
 +
<references/>
 +
<br/>
 +
 
 +
==={{Bilingual|真核生物のオキシドスクアレン環化酵素|Oxidosqualene Cyclase in Eukaryotes}}===
 
{{Twocolumn|
 
{{Twocolumn|
 
Any path of reactions from the root (2,3-oxidosqualene) to any triterpene backbone with a colored background is catalyzed by a single enzyme called ''oxidosqualene cyclase'' (OSC) or ''terpene synthase h'' (tpsh).<ref>Terpene synthases a-f are responsible for mono-, sesquie- and diterpenes. Tps g is the squalene cyclase.</ref>
 
Any path of reactions from the root (2,3-oxidosqualene) to any triterpene backbone with a colored background is catalyzed by a single enzyme called ''oxidosqualene cyclase'' (OSC) or ''terpene synthase h'' (tpsh).<ref>Terpene synthases a-f are responsible for mono-, sesquie- and diterpenes. Tps g is the squalene cyclase.</ref>
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{|
 
{|
 
|-
 
|-
−
! {{Bilingual|Backbone Color Code: |骨格色分け: }}
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! {{Bilingual|骨格色分け:|Backbone Color Code:}}
 
! style="background-color:#fdd"| Animals, fungi, and yeast
 
! style="background-color:#fdd"| Animals, fungi, and yeast
 
! style="background-color:#dfd"| Plants only
 
! style="background-color:#dfd"| Plants only
 
!  
 
!  
 
|-
 
|-
−
! {{Bilingual|Six-membered rings: |6員環表記: }}
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! {{Bilingual|6員環表記:|Six-membered rings:}}
 
! colspan="2" | chair (C), or boat (B)  
 
! colspan="2" | chair (C), or boat (B)  
 
|}
 
|}
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|colspan="2" align="right"|
 
|colspan="2" align="right"|
 
{|
 
{|
−
|lanosterol/<br/>cycloartenol<br/>syntase<ref>Lanosterol synthase is the most accessible enzyme among oxidosqualene cyclases, e.g. from mammalian liver or yeast. Cycloartenol synthase is the basic OSC in plants, although lanosterol synthase is also found. For the grouping of cyclases, check Xiong Q et al. (2005) in this page.<br/>''Ref.''
+
|lanosterol/<br/>cycloartenol<br/>syntase<ref>Lanosterol synthase is the most accessible enzyme among oxidosqualene cyclases, e.g. from mammalian liver or yeast. Cycloartenol synthase is the basic OSC in plants, although lanosterol synthase is also found. For the grouping of cyclases, check the review by Xiong Q et al. (2005) in this page.<br/>''References.''
 
* Corey EJ, Russey WE, Ortiz-de-Montellano PR (1966) 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene ''J Am Chem Soc'' 88:4750-1
 
* Corey EJ, Russey WE, Ortiz-de-Montellano PR (1966) 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene ''J Am Chem Soc'' 88:4750-1
−
* Kolesnikova MD, Xiong Q, Lodeiro S, Hua L, Matsuda SPT (2006) Lanosterol biosynthesis in plants ''Arch Biochem Biophys'' 447:87-95</ref>
+
* Kolesnikova MD, Xiong Q, Lodeiro S, Hua L, Matsuda SPT (2006) Lanosterol biosynthesis in plants ''Arch Biochem Biophys'' 447:87-95<br/>
 +
In ''Arabidopsis'', cycloartenol synthase can be converted to lanosterol synthase with only two amino acid substitutions: His477 to Asn and Ile481 to Val. Tyr410 is also important for specificity.
 +
* Lodeiro S, Schulz-Gasch T, Matsuda SPT (2005) Enzyme redesign: two mutations cooperate to convert cycloartenol synthase into an accurate lanosterol synthase ''J Am Chem Soc'' 127:14132-14133
 +
</ref>
 
|[[Image:Arrow00dl35.png]]
 
|[[Image:Arrow00dl35.png]]
 
|stepwise<br/>cyclization<ref>The cyclization process is stepwise, not concerted as previously thought. As one clue, squalene is not fully folded in the cyclase active site.<br/>''Ref.'' Reinert DJ, Balliano G, Schulz GE (2004) Conversion of squalene to the pentacarbocyclic hopene. ''Chem Biol'' 11:121-6</ref>
 
|stepwise<br/>cyclization<ref>The cyclization process is stepwise, not concerted as previously thought. As one clue, squalene is not fully folded in the cyclase active site.<br/>''Ref.'' Reinert DJ, Balliano G, Schulz GE (2004) Conversion of squalene to the pentacarbocyclic hopene. ''Chem Biol'' 11:121-6</ref>
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|align="left"|
 
|align="left"|
 
{|
 
{|
−
|lupeol<br/>synthase
+
|lupeol/<br/>&beta;-amyrin<br/>synthase<ref>Lupeol synthases are found in [[Species:Glycyrrhiza|''Glycyrrhiza glabra'']], [[Species:Betula|''Betula'' platyphylla]], [[Species:Taraxacum|''Taraxacum officinale'']], and [[Species:Olea|''Olea europea'']]. They form a clade (74-81% identical) that is distinct from other OSCs. Lupeol synthase evolved before the divergence of asterids and eurosids. On the other hand, &beta;-amyrin synthases are considerably more distant (48-50% identical) than are the CAS enzymes (70-79% identical). &beta;-amyrin synthases in eudicotsa nd monocots may have independent origins.<ul><li>Haralampidis K, Bryan G, Qi X, Papadopoulou K, Bakht S, Melton R, Osbourn A (2001) A new class of oxidosqualene cyclases directs synthesis of antimicrobial phytoprotectants in monocots ''Proc Natl Acad Sci U S A'' 98(23):13431-6 <li>Qi X, Bakht S, Leggett M, Maxwell C, Melton R, Osbourn A (2004) A gene cluster for secondary metabolism in oat: implications for the evolution of metabolic diversity in plants ''Proc Natl Acad Sci U S A'' 101(21):8233-8</ul></ref>
 
|[[Image:Arrow00dr35.png]]
 
|[[Image:Arrow00dr35.png]]
 
|stepwise<br/>cyclization
 
|stepwise<br/>cyclization
 
|}
 
|}
 
|-
 
|-
−
| 17&beta;-protosteryl cation <small>(C-B-C)</small><ref>The C-17 chain of rotosteryl cation is &beta;-configuration, not &alpha;.<br/> ''Ref.'' Corey EJ, Virgil SC (1991) An experimental demonstration of the stereochemistry of enzymic cyclization of 2,3-oxidosqualene to the protosterol system, forerunner of lanosterol and cholesterol. [http://pubs.acs.org/doi/abs/10.1021/ja00010a073 ''J Am Chem Soc'' 113:4025-6]</ref> <br/>[[Image:Protosteryl cation.png]]
+
| 17&beta;-protosteryl cation <small>(C-B-C)</small><ref>The C-17 chain of rotosteryl cation is &beta;-configuration, not &alpha;.<br/> ''Ref.'' Corey EJ, Virgil SC (1991) An experimental demonstration of the stereochemistry of enzymic cyclization of 2,3-oxidosqualene to the protosterol system, forerunner of lanosterol and cholesterol. [http://pubs.acs.org/doi/abs/10.1021/ja00010a073 ''J Am Chem Soc'' 113:4025-6]</ref> <br/>[[Image:Protosteryl cation.png|150px]]
 
| 1,2-shift<br/>[[Image:Arrow00r.png]]
 
| 1,2-shift<br/>[[Image:Arrow00r.png]]
−
| colspan="2"|lanosteryl cation <small>(C-C-C)</small><br/>[[Image:Lanosteryl cation.png]]
+
| colspan="2" align="left"|lanosteryl cation <small>(C-B-C)</small><br/>[[Image:Lanosteryl cation.png|150px]]
−
| 17&beta;-dammarenyl cation <small>(C-C-C)</small><ref>The C-17 chain of dammarenyl cation is &beta;-configuration.<br/> ''Ref.'' Xiong Q, Rocco F, Wilson WK, Xu R, Ceruti M, Matsuda SPT (2005) Structure and reactivity of the dammarenyl cation: configuration transmission in triterpene synthesis. ''J Org. Chem. 70:5362-75</ref> <br/>[[Image:Dammarenyl cation.png]]
+
| 17&beta;-dammarenyl cation <small>(C-C-C)</small><ref>The C-17 chain of dammarenyl cation is &beta;-configuration.<br/> ''Ref.'' Xiong Q, Rocco F, Wilson WK, Xu R, Ceruti M, Matsuda SPT (2005) Structure and reactivity of the dammarenyl cation: configuration transmission in triterpene synthesis. ''J Org. Chem. 70:5362-75</ref> <br/>[[Image:Dammarenyl cation.png|150px]]
 
|-
 
|-
 
|colspan="2"|
 
|colspan="2"|
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|}
 
|}
 
|- valign="top"
 
|- valign="top"
−
|colspan="2"| cation with the chain at C18 or C17 position<br/>[[Image:CBCC cation.png]]or [[Image:CBCC cation2.png]]
+
|colspan="2"| cation with the chain at C18 or C17 position<br/>[[Image:CBCC cation.png|150px]]or [[Image:CBCC cation2.png|100px]]
 
|
 
|
 
{|
 
{|
 
|style="background-color:#fdd"| all steroids<br/>lanostane<br/>cycloartane<br/>cucurbitane<br/>ergostane etc.
 
|style="background-color:#fdd"| all steroids<br/>lanostane<br/>cycloartane<br/>cucurbitane<br/>ergostane etc.
 
|}
 
|}
−
|align="right"|
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|style="vertical-align:bottom"|
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{|
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{| style="margin-left:auto;margin-right:0;"
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|<br/><br/><br/>
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−
|-
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|style="background-color:#dfd"| baccharane<br/>shionane
 
|style="background-color:#dfd"| baccharane<br/>shionane
 
| [[Image:Arrow00l35.png]]
 
| [[Image:Arrow00l35.png]]
 
|}
 
|}
−
| baccarenyl cation <small>(C-C-C-C)</small><br/>[[Image:Baccarenyl cation.png]]
+
| baccarenyl cation <small>(C-C-C-C)</small><br/>[[Image:Baccarenyl cation.png|150px]]
 
|-
 
|-
 
|
 
|
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|}
 
|}
 
|
 
|
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|align="right"|
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|
−
{|
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{| style="margin-left:auto;margin-right:0;"
 
| E-ring cyclization<br/>(from 17&alpha;/&beta;)
 
| E-ring cyclization<br/>(from 17&alpha;/&beta;)
 
| [[Image:Arrow00dl.png]]
 
| [[Image:Arrow00dl.png]]
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|}
 
|}
 
|- valign="top"
 
|- valign="top"
−
| arborinyl cation <small>(C-B-C-C)</small><br/>[[Image:Arborinyl cation.png]]  
+
| arborinyl cation <small>(C-B-C-C)</small><br/>[[Image:Arborinyl cation.png|150px]]  
−
| colspan="2" align="left"| unnamed cation <small>(C-B-C-C)</small><br/>[[Image:Hanco cation.png]]
+
| colspan="2" align="left"| unnamed cation <small>(C-B-C-C)</small><br/>[[Image:Hanco cation.png|150px]]
−
| 21&alpha;-hopyl cation <small>(C-C-C-C)</small><br/>21&beta;-moretyl cation <small>(C-C-C-C)</small><ref>The 21''R'' stereocenter is usually lost in hydride shift.</ref><br/>[[Image:Hopyl cation.png]]
+
| 21&alpha;-hopyl cation <small>(C-C-C-C)</small><br/>21&beta;-moretyl cation <small>(C-C-C-C)</small><ref>The 21''R'' stereocenter is usually lost in hydride shift.</ref><br/>[[Image:Hopyl cation.png|150px]]
−
| H18&alpha;-lupyl cation <small>(C-C-C-C)</small><br/>H18&beta;-lupyl cation <small>(C-C-C-B)</small><br/>[[Image:Lupyl cation.png]]
+
| H18&alpha;-lupyl cation <small>(C-C-C-C)</small><br/>H18&beta;-lupyl cation <small>(C-C-C-B)</small><br/>[[Image:Lupyl cation.png|150px]]
 
|-
 
|-
 
|align="left"|  
 
|align="left"|  
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|
 
|
 
|style="background-color:#dfd" align="left"| hopane (C-C-C-C)<br/> gammacerane (C-C-C-C-C)<br/> fernane (C-C-C-C)<br/> swertane (C-C-C-C-C)<br/>
 
|style="background-color:#dfd" align="left"| hopane (C-C-C-C)<br/> gammacerane (C-C-C-C-C)<br/> fernane (C-C-C-C)<br/> swertane (C-C-C-C-C)<br/>
−
|style="background-color:#dfd" align="left"| oleanane (C-C-C-C-C)<br/> lupane (C-C-C-C)<br/> germanicane<br/> taraxastane (C-C-C-C-C)<br/> ursane (C-C-C-C-C/B)<br/> friedomadeirane (C-C-C-C)<ref>E-ring cyclization precedes D-ring expansion.</ref><br/>  
+
|style="background-color:#dfd" align="left"| oleanane<ref>&beta;-amyrin has the oleanane skeleton</ref> (C-C-C-C-C)<br/> lupane (C-C-C-C)<br/> germanicane<br/> taraxastane (C-C-C-C-C)<br/> ursane (C-C-C-C-C/B)<br/> friedomadeirane (C-C-C-C)<ref>E-ring cyclization precedes D-ring expansion.</ref><br/>  
 
|}
 
|}
  
 
</center>
 
</center>
  
−
<references/>
+
{| class="wikitable collapsible" style="width:100%"
−
 
+
! References
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+
|-
−
Reviews:
+
| <references/>
 +
|-
 +
! Reviews
 +
|-
 +
|
 
* Xu R, Fazio GC, Matsuda SPT (2004) On the origins of triterpenoid skeletal diversity. ''Phytochemstry'' 65:261-291 PMID 14751299
 
* Xu R, Fazio GC, Matsuda SPT (2004) On the origins of triterpenoid skeletal diversity. ''Phytochemstry'' 65:261-291 PMID 14751299
 
* Philips DR, Rasbery JM, Bartel B, Matuda SPT (2006) Biosynthetic diversity in plant triterpene cyclization ''Curr Opin Plant Biol'' 9:305-314
 
* Philips DR, Rasbery JM, Bartel B, Matuda SPT (2006) Biosynthetic diversity in plant triterpene cyclization ''Curr Opin Plant Biol'' 9:305-314
 +
|}
  
−
==={{Bilingual|Squalene Cyclase in Bacteria and Ferns|バクテリア・シダ類のスクアレン環化酵素}}===
+
==={{Bilingual|バクテリア・シダ類のスクアレン環化酵素|Squalene Cyclase in Bacteria and Ferns}}===
  
 
{{Twocolumn|
 
{{Twocolumn|
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{| style="text-align:center"
 
{| style="text-align:center"
−
| squalene<br/>[[Image:squalene.png]]
+
| squalene<br/>[[Image:squalene.png|150px]]
 
| [[Image:Arrow00r.png]]<br/>squalene-hopene cyclase<ref>SH cyclase is the most investigated enzyme among squalene cyclases. <br/>''Ref.'' Kannenberg EL, Poralla K (1999) Hopanoid biosyntehsis and function in bacteria. ''Naturwissenschaften'' 86:168-76.</ref>
 
| [[Image:Arrow00r.png]]<br/>squalene-hopene cyclase<ref>SH cyclase is the most investigated enzyme among squalene cyclases. <br/>''Ref.'' Kannenberg EL, Poralla K (1999) Hopanoid biosyntehsis and function in bacteria. ''Naturwissenschaften'' 86:168-76.</ref>
 
| 17&alpha;-deoxydammarenyl cation<ref>The C-17 chain of deoxydammarenyl cation is &alpha;-configuration, not &beta; as in eukaryotes.<br/>
 
| 17&alpha;-deoxydammarenyl cation<ref>The C-17 chain of deoxydammarenyl cation is &alpha;-configuration, not &beta; as in eukaryotes.<br/>
−
''Ref.'' Wendt KU, Schulz GE, Corey EJ, Liu DR (2000) Enzyme mechanisms for polycyclic triterpene formation. [http://www3.interscience.wiley.com/journal/72515653/abstract?CRETRY=1&SRETRY=0 ''Angew Chem, Int Ed'' 39:2812-33]</ref> <br/>[[Image:Deoxydammarenyl cation.png]]
+
''Ref.'' Wendt KU, Schulz GE, Corey EJ, Liu DR (2000) Enzyme mechanisms for polycyclic triterpene formation. [http://www3.interscience.wiley.com/journal/72515653/abstract?CRETRY=1&SRETRY=0 ''Angew Chem, Int Ed'' 39:2812-33]</ref> <br/>[[Image:Deoxydammarenyl cation.png|150px]]
 
|-
 
|-
 
|
 
|
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|}
 
|}
 
|-
 
|-
−
|style="background-color:#ddf"| hopene<br/>[[Image:Hopene.png]]
+
|style="background-color:#ddf"| hopene<br/>[[Image:Hopene.png|150px]]
 
| [[Image:Arrow00l.png]]
 
| [[Image:Arrow00l.png]]
−
| hopyl cation <br/>[[Image:Hopyl cation.png]]
+
| hopyl cation (c-c-c-c)<br/>[[Image:Hopyl cation.png|150px]]
 
|}
 
|}
  
 
{{Twocolumn|
 
{{Twocolumn|
−
Hopanoids are widespread: they are found in bacteria, ferns, and geological sediments.
+
Hopanoids are widespread: they are found in bacteria, ferns, and geological sediments. They are not found, however, in archaea or animals.
 +
 
 
|
 
|
−
ホパノイドはバクテリアだけでなく、シダ類や地下堆積物からも見つかっています。
+
ホパノイドはバクテリアだけでなく、シダ類や地下堆積物からも見つかっています。しかしアーキアや動物からは見つかっていません。
 
}}
 
}}
  
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<references/>
 
<references/>
  
−
==={{Bilingual|Bis-oxidosqualene Cyclase|ビスオキシドスクアレン環化酵素}}===
+
==={{Bilingual|ビスオキシドスクアレン環化酵素|Bis-oxidosqualene Cyclase}}===
 
{{Twocolumn|
 
{{Twocolumn|
 
Squalene is oxidized by squalene oxidase to become 2,3-oxidosqualene.
 
Squalene is oxidized by squalene oxidase to become 2,3-oxidosqualene.
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<references/>
 
<references/>
  
−
=={{Bilingual|Design of Tri-terpene ID numbers|ID番号の設計}}==
+
=={{Bilingual|ID番号の設計|Design of Tri-terpene ID numbers}}==
 
<center>
 
<center>
 
12-DIGIT
 
12-DIGIT

Latest revision as of 11:55, 8 December 2012

Contents

[edit] Triterpene (C30)

[edit] Ring configuration

[edit] Steroid

The basic structure is 4 carbon rings, cyclopenta[a]phenanthrene, gonane, or sterane. The rings B/C are always trans in all natural steroids. If the rings C/D are trans, it is called gonane. If its stereochemistry is unspecified, it is called sterane. Most steroids take gonane form, but in cardenolides and bufanolides, the rings C/D are cis.

Cyclopenta-a-phenanthrene.png Gonane.png
Cyclopenta[a]phenanthrene Gonane

The majority of steroids have methyl groups sticking out from the bridgehead positions C-10 and C-13. When these methyl groups (or hydrogens) stand above the plane, they are called β-configuration. Those below the plane are called α-configuration. If the configuration at any site is unknown, it is indicated as ξ (Greek Xi). By default, hydrogen atoms or substituents at the positions C-8, 9, 10, 13, and 14 are assumed to be 8β, 9α, 10β, 13β, and 14α configurations. C-5 is a special position, because there are as many 5α steroids as 5β are.

Cholestane.png 5alpha-steroid.png 5beta-steroid.png
cholestane backbone 5α-configuration 5β-configuration

[edit] Triterpenes

In almost all pentacyclic triterpenes in angiosperms, the methyl group at the DE-ring fusion is β-configuration. Some triterpenes in ferns, mosses, gymnosperms have α-methyl group at the DE-ring fusion.

[edit] Biosynthesis

[edit] Overview

The starting point is squalene, which is formed by joining two FPPs tail-to-tail. Bacterial cyclases use squalene directly[1], but those of the other species use 2,3-oxidosqualene for cyclization.

Squalene.png 2,3-oxidosqualene.png
squalene 2,3-oxidosqualene

  • In bacteria, squalene is cyclized via the 17α-deoxydammarenyl cation to hopene and other triterpenes.
  • In eukaryotes, 2,3-oxidosqualene is cyclized via the protosteryl cation to lanosterol (animals and fungi), cycloartenol (plants) or parkeol (sea cucumbers) by a series of 1,2-hydride and methyl shifts (Wagner-Meerwein shifts).
  • In plants, a trace amount of phytosterols comes from lanosterol [2] At3g45130 is lanosterol synthase in Arabidopsis and its orthologs exist in asterids Taraxacum officinale and Panax ginseng and eurosid Luffa cylindrica. Lanosterol synthase exists broadly among eudicots [3]. Parkeol is also widespread in plants.
  • In plants, various triterpenes arise from the 17β-dammarenyl cation.

References
  1. ↑ Bacterial squalene cyclases can accept oxidosqualene as their substrates, but oxidosqualene usually does not exist in bacteria
  2. ↑ Ohyama K, Suzuki M, Kikuchi J, Saito K, Muranaka T (2009) Dual biosynthetic pathways to phytosterol via cycloartenol and lanosterol in Arabidopsis Proc Natl Acad Sci USA 106(3):725-730
  3. ↑ Kolesnikova MD, Xiong Q, Lodeiro S, Hua L, Matsuda SPT (2006) Lanosterol biosynthesis in plants Arch Biochem Biophys 447:87-95


[edit] Oxidosqualene Cyclase in Eukaryotes

Any path of reactions from the root (2,3-oxidosqualene) to any triterpene backbone with a colored background is catalyzed by a single enzyme called oxidosqualene cyclase (OSC) or terpene synthase h (tpsh).[1]

Backbone Color Code: Animals, fungi, and yeast Plants only
Six-membered rings: chair (C), or boat (B)
2,3-oxidosqualene
2,3-oxidosqualene.png
lanosterol/
cycloartenol
syntase[2] 		Arrow00dl35.png stepwise
cyclization[3]
lupeol/
β-amyrin
synthase[4] 		Arrow00dr35.png stepwise
cyclization
17β-protosteryl cation (C-B-C)[5]
Protosteryl cation.png 		1,2-shift
Arrow00r.png 		lanosteryl cation (C-B-C)
Lanosteryl cation.png 		17β-dammarenyl cation (C-C-C)[6]
Dammarenyl cation.png
D-ring
expansion 		Arrow00d.png
Arrow00dr35.png fungus
only[7]
protostane
1,2-shifts Arrow00d.png all eukaryotes
D-ring
expansion 		Arrow00d.png Arrow00dr35.png

 dammarane
euphane
tirucalane etc.[8]
cation with the chain at C18 or C17 position
CBCC cation.pngor CBCC cation2.png
all steroids
lanostane
cycloartane
cucurbitane
ergostane etc.
baccharane
shionane 		Arrow00l35.png
baccarenyl cation (C-C-C-C)
Baccarenyl cation.png
E-ring
cyclization
(from 17β) 		Arrow00d.png No 17α known
in nature [9]
E-ring
cyclization
(from 18α) 		Arrow00d.png
E-ring cyclization
(from 17α/β) 		Arrow00dl.png
E-ring cyclization
(from 18α/β) 		Arrow00d.png
arborinyl cation (C-B-C-C)
Arborinyl cation.png 		unnamed cation (C-B-C-C)
Hanco cation.png 		21α-hopyl cation (C-C-C-C)
21β-moretyl cation (C-C-C-C)[10]
Hopyl cation.png 		H18α-lupyl cation (C-C-C-C)
H18β-lupyl cation (C-C-C-B)
Lupyl cation.png
1,2-shifts Arrow00d35.png E-ring expansion
1,2-shifts Arrow00d35.png E-ring expansion
1,2-shifts Arrow00d35.png E-ring expansion
1,2-shifts Arrow00d35.png E-ring expansion
arborinane (C-B-C-C)
stictane (C-B-C-C-C)[11] 		hancokinane (C-B-C-C) hopane (C-C-C-C)
gammacerane (C-C-C-C-C)
fernane (C-C-C-C)
swertane (C-C-C-C-C)
 oleanane[12] (C-C-C-C-C)
lupane (C-C-C-C)
germanicane
taraxastane (C-C-C-C-C)
ursane (C-C-C-C-C/B)
friedomadeirane (C-C-C-C)[13]
References
  1. ↑ Terpene synthases a-f are responsible for mono-, sesquie- and diterpenes. Tps g is the squalene cyclase.
  2. ↑ Lanosterol synthase is the most accessible enzyme among oxidosqualene cyclases, e.g. from mammalian liver or yeast. Cycloartenol synthase is the basic OSC in plants, although lanosterol synthase is also found. For the grouping of cyclases, check the review by Xiong Q et al. (2005) in this page.
    References.
    • Corey EJ, Russey WE, Ortiz-de-Montellano PR (1966) 2,3-Oxidosqualene, an intermediate in the biological synthesis of sterols from squalene J Am Chem Soc 88:4750-1
    • Kolesnikova MD, Xiong Q, Lodeiro S, Hua L, Matsuda SPT (2006) Lanosterol biosynthesis in plants Arch Biochem Biophys 447:87-95
    In Arabidopsis, cycloartenol synthase can be converted to lanosterol synthase with only two amino acid substitutions: His477 to Asn and Ile481 to Val. Tyr410 is also important for specificity.
    • Lodeiro S, Schulz-Gasch T, Matsuda SPT (2005) Enzyme redesign: two mutations cooperate to convert cycloartenol synthase into an accurate lanosterol synthase J Am Chem Soc 127:14132-14133
  3. ↑ The cyclization process is stepwise, not concerted as previously thought. As one clue, squalene is not fully folded in the cyclase active site.
    Ref. Reinert DJ, Balliano G, Schulz GE (2004) Conversion of squalene to the pentacarbocyclic hopene. Chem Biol 11:121-6
  4. ↑ Lupeol synthases are found in Glycyrrhiza glabra, Betula platyphylla, Taraxacum officinale, and Olea europea. They form a clade (74-81% identical) that is distinct from other OSCs. Lupeol synthase evolved before the divergence of asterids and eurosids. On the other hand, β-amyrin synthases are considerably more distant (48-50% identical) than are the CAS enzymes (70-79% identical). β-amyrin synthases in eudicotsa nd monocots may have independent origins.
    • Haralampidis K, Bryan G, Qi X, Papadopoulou K, Bakht S, Melton R, Osbourn A (2001) A new class of oxidosqualene cyclases directs synthesis of antimicrobial phytoprotectants in monocots Proc Natl Acad Sci U S A 98(23):13431-6
    • Qi X, Bakht S, Leggett M, Maxwell C, Melton R, Osbourn A (2004) A gene cluster for secondary metabolism in oat: implications for the evolution of metabolic diversity in plants Proc Natl Acad Sci U S A 101(21):8233-8
  5. ↑ The C-17 chain of rotosteryl cation is β-configuration, not α.
    Ref. Corey EJ, Virgil SC (1991) An experimental demonstration of the stereochemistry of enzymic cyclization of 2,3-oxidosqualene to the protosterol system, forerunner of lanosterol and cholesterol. J Am Chem Soc 113:4025-6
  6. ↑ The C-17 chain of dammarenyl cation is β-configuration.
    Ref. Xiong Q, Rocco F, Wilson WK, Xu R, Ceruti M, Matsuda SPT (2005) Structure and reactivity of the dammarenyl cation: configuration transmission in triterpene synthesis. J Org. Chem. 70:5362-75
  7. ↑ Oxygenated protostane are known in Cephalosporium caerulens, Fusidium coccineum, and Aspergillus fumigatus (Ascomycota).
    Ref. Hattori H, Igarashi H, Iwasaki S, Okuda S, (1969) Isolation of 3bhydroxy- 4b-methylfusida-17(20)[16,21-cis],24 diene (3b-hydroxyprotosta- 17(20)[16,21-cis],24 diene) and a related triterpene alcohol Tetrahedron Lett 13, 1023–1026
    Tiwari KP, Choudhary RN (1981) Chemical examination of Wisteria sinensis Proc Natl Acad Sci India A 51, 263–271
  8. ↑ Dammarane derivatives are unusually prevalent in the genus Euphorbia.
  9. ↑ No 17α cyclization for the ring-B boat form. Also no squalene cyclase is known for the ring-B boat form.
    Ref. Xiong Q, Rocco F, Wilson WK, Xu R, Ceruti M, Matsuda SPT (2005) Structure and reactivity of the dammarenyl cation: configurational transmission in triterpene synthesis. J Org Chem 70:5362-75
  10. ↑ The 21R stereocenter is usually lost in hydride shift.
  11. ↑ C-B-C-C-C rings are very rare and stictanediol from Ascomycota Sticta genus is the sole example.
    Ref. Chin WJ, Corbett RE, Heng CK, Wilkins AL (1973) Lichens and fungi. XI. Isolation and structural elucidation of a new group of triterpenes from Sticta coronata, S. colensoi, and S. flavicans. J Chem Soc Perkin Trans 1:1437–46
  12. ↑ β-amyrin has the oleanane skeleton
  13. ↑ E-ring cyclization precedes D-ring expansion.
Reviews
  • Xu R, Fazio GC, Matsuda SPT (2004) On the origins of triterpenoid skeletal diversity. Phytochemstry 65:261-291 PMID 14751299
  • Philips DR, Rasbery JM, Bartel B, Matuda SPT (2006) Biosynthetic diversity in plant triterpene cyclization Curr Opin Plant Biol 9:305-314

[edit] Squalene Cyclase in Bacteria and Ferns

Squalene cyclase (SC) or terpene synthase g (tpsg) are found in prokaryotes, ciliates, and lower plants (mosses and ferns) and can convert squalene, which is symmetric, as well as 2,3-oxidosqualene. Main products are hopanol and tetrahymanol, and only generate all-chair cations.

squalene
Squalene.png 		Arrow00r.png
squalene-hopene cyclase[1] 		17α-deoxydammarenyl cation[2]
Deoxydammarenyl cation.png
D-ring
expansion 		Arrow00d35.png E-ring cyclization
from 17α
hopene
Hopene.png 		Arrow00l.png hopyl cation (c-c-c-c)
Hopyl cation.png

Hopanoids are widespread: they are found in bacteria, ferns, and geological sediments. They are not found, however, in archaea or animals.

Almost all mono-, di-, tri- and tetracyclic terpenes from squalene are found in ferns: Polypodium, Lemmaphyllum, and Pyrrosia. Notable exception is Z-Dammara-17(20),24-diene from moss Floribundaria[3]. Pentacyclic terpenes from squalene, on the other hand, are found also in angiosperms such as Achillea, Erysimum, Castanopsis and in Ascomycota.

  1. ↑ SH cyclase is the most investigated enzyme among squalene cyclases.
    Ref. Kannenberg EL, Poralla K (1999) Hopanoid biosyntehsis and function in bacteria. Naturwissenschaften 86:168-76.
  2. ↑ The C-17 chain of deoxydammarenyl cation is α-configuration, not β as in eukaryotes.
    Ref. Wendt KU, Schulz GE, Corey EJ, Liu DR (2000) Enzyme mechanisms for polycyclic triterpene formation. Angew Chem, Int Ed 39:2812-33
  3. ↑ Toyota M, Masuda K, Asakawa Y (1998) Triterpenoid constituents of the moss Floribundaria aurea subsp. nipponica. Phytochemistry 48:297–299

[edit] Bis-oxidosqualene Cyclase

Squalene is oxidized by squalene oxidase to become 2,3-oxidosqualene. Further epoxidation of this symmetric molecule produces 2,3-(S)-22,23-(S)-bis-oxidosqualene, which is converted to 24,25-epoxylanostan-3-ol or 24,25-epoxycycloartan-3-ol. Epoxylanosterol is known to negatively regulate sterol biosynthesis[1].

2,3-oxidosqualene.png 2,3-22,23-bis-oxidosqualene.png
2,3-oxidosqualene 2,3-22,23-bis-oxidosqualene
  1. ↑ Gardner RG, Shan H, Matsuda SPT, Hampton RY (2001) A positive oxysterol-derived signal for 3-hydroxy-3-methylglutaryl CoA reductase degradation in yeast. J Biol Chem 276:8681–869

[edit] Design of Tri-terpene ID numbers

12-DIGIT

T P 3 x y y r h g n c c
x ... species information
Symbol at x Kingdom Phyla Examples
I Animalia Arthropoda (Insects, crabs) ecdysteroids
V Chordate (Vertebrates) sex steroids, corticosteroids, anabolic steroids
O Others marine steroids
P Plantae Phytosterols lanosterols, cholesterols, brassinolides
S Saponins saponins
F Fungi ergosterols ergosterols
B Bacteria bacterial sterols hopanoids
y ... backbone structure (母核構造) 
Symbol at y Carbons Steroids Backbone Structure
GN C17 gonane Gonane.png
ES C18 estrane Estrane.png
AD C19 androstane Androstane.png
PG C21 pregnane Pregnane.png
CA C24 cholane Cholane.png
CL C27 cholestane Cholestane.png
CM C28 campestane Campestane.png
EG C28 ergostane Ergostane.png
SG C29 (4 rings) stigmastane Stigmastane.png
PR C29 (4 rings) poriferastane Poriferastane.png
Symbol at y Carbons Triterpenoids Backbone Structure
PS C30 protostane Protostane.png
EU C30 euphane Euphane.png
LN C30 lanostane Lanostane.png
CY C30 cycloartane Cycloartane.png
FS C29 fusidane Fusidane.png
HP C30 (5 rings) hopane Hopane.png
FN C30 (5 rings) fernane Fernane.png
CC C30 cucurbitane Cucurbitane.png
DM C30 dammarane Dammarane.png
BC C30 baccharane Baccharane.png
HL C30 holostane Holostane.png
PF C29 (5 rings) pfaffane Pfaffane.png
LP C30 (5 rings) lupane Lupane.png
OL C30 (5 rings) oleanane Oleanane.png
FD C30 (5 rings) friedelane Friedelane.png
TR C30 (5 rings) taraxastane Taraxastane.png
UR C30 (5 rings) ursane Ursane.png
SR C30 (5 rings) serratane Serratane.png


r ... number of major rings (環構造数) 

Click above categories to see details.

h ... hydroxylation pattern (水酸基数) 

Click above categories to see details.

g ... glycosylation pattern(糖修飾パターン) 

Click above categories to see details.

n ... number of sugars (修飾糖数) 

Click above categories to see details.

c ... serial number (通し番号)

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