Radicicol: Difference between revisions

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== Biosynthesis ==
== Biosynthesis ==
Biosynthesis of Radicicol has been best studied in ''[[Pochonia chlamydosporia]]'', in which the majority of the core structure is produced in vivo through iterative type I [[polyketide synthases]].<ref>{{cite journal | doi = 10.1074/jbc.M110.183574 | volume=285 | title=Insights into Radicicol Biosynthesis via Heterologous Synthesis of Intermediates and Analogs | journal=Journal of Biological Chemistry | pages=41412–41421 | pmid=20961859 | pmc=3009867 | vauthors=Zhou H, Qiao K, Gao Z, Vederas JC, Tang Y}}</ref> This structure produced is the earliest intermediate in the radicicol biosynthesis, monocillin II. This intermediate is transformed to radicicol through halogenation and epoxide formation performed by RadH and RadP respectively.<ref>{{cite journal | doi = 10.1016/j.chembiol.2008.10.006 | volume=15 | title=Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii | journal=Chemistry | pages=1328–1338| doi-access=free }}</ref> These enzymes are coded by the genes Rdc2 and Rdc4 in the pathway, and removing either of these results in a product that has the monocillin II core, but does not have either the epoxide or halogen added.<ref>{{cite journal | doi = 10.1016/j.chembiol.2008.10.006 | volume=15 | title=Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii | journal=Chemistry | pages=1328–1338| doi-access=free }}</ref>
Biosynthesis of Radicicol has been best studied in ''[[Pochonia chlamydosporia]]'', in which the majority of the core structure is produced in vivo through iterative type I [[polyketide synthases]].<ref>{{cite journal | doi = 10.1074/jbc.M110.183574 | volume=285 | title=Insights into Radicicol Biosynthesis via Heterologous Synthesis of Intermediates and Analogs | journal=Journal of Biological Chemistry | pages=41412–41421 | pmid=20961859 | pmc=3009867 | vauthors=Zhou H, Qiao K, Gao Z, Vederas JC, Tang Y| year=2010 | issue=53 }}</ref> This structure produced is the earliest intermediate in the radicicol biosynthesis, monocillin II. This intermediate is transformed to radicicol through halogenation and epoxide formation performed by RadH and RadP respectively.<ref>{{cite journal | doi = 10.1016/j.chembiol.2008.10.006 | volume=15 | title=Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii | journal=Chemistry | year=2008 | pages=1328–1338| doi-access=free | last1=Wang | first1=Shuhao | last2=Xu | first2=Yuquan | last3=Maine | first3=Erin A. | last4=Wijeratne | first4=E.M. Kithsiri | last5=Espinosa-Artiles | first5=Patricia | last6=Gunatilaka | first6=A.A. Leslie | last7=Molnár | first7=István | issue=12 }}</ref> These enzymes are coded by the genes Rdc2 and Rdc4 in the pathway, and removing either of these results in a product that has the monocillin II core, but does not have either the epoxide or halogen added.<ref>{{cite journal | doi = 10.1016/j.chembiol.2008.10.006 | volume=15 | title=Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii | journal=Chemistry | year=2008 | pages=1328–1338| doi-access=free | last1=Wang | first1=Shuhao | last2=Xu | first2=Yuquan | last3=Maine | first3=Erin A. | last4=Wijeratne | first4=E.M. Kithsiri | last5=Espinosa-Artiles | first5=Patricia | last6=Gunatilaka | first6=A.A. Leslie | last7=Molnár | first7=István | issue=12 }}</ref>


[[File:Proposed Radicicol Biosynthetic Pathway.png|thumb|400px|left|Proposed biosynthetic pathway of Radicicol.]]{{clear left}}
[[File:Proposed Radicicol Biosynthetic Pathway.png|thumb|400px|left|Proposed biosynthetic pathway of Radicicol.]]{{clear left}}
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==Further reading==
==Further reading==
*{{cite journal |vauthors=Winssinger N, Barluanga S |title=Chemistry and biology of resorcylic acid lactones |journal=Chem Commun |volume= 13|issue=1 |pages=22–36 |date=January 2007 |doi=10.1039/B610344H }} Review of the chemistry and biology of resorcylic acid lactones, including radicicol.
*{{cite journal |vauthors=Winssinger N, Barluanga S |title=Chemistry and biology of resorcylic acid lactones |journal=Chem Commun |volume= 13|issue=1 |pages=22–36 |date=January 2007 |doi=10.1039/B610344H |pmid=17279252 }} Review of the chemistry and biology of resorcylic acid lactones, including radicicol.


[[Category:Epoxides]]
[[Category:Epoxides]]

Revision as of 06:58, 8 February 2021

Radicicol
Names
IUPAC name
(1aR,2E4E,14R,15aR)-8-chloro-9,11-dihydroxy-14-methyl-1a,14,15,15a-tetrahydro-6H-oxireno[e][2]benzoxacyclotetradecine-6,12(7H)-dione
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.170.695 Edit this at Wikidata
UNII
  • InChI=1S/C18H17ClO6/c1-9-6-15-14(25-15)5-3-2-4-10(20)7-11-16(18(23)24-9)12(21)8-13(22)17(11)19/h2-5,8-9,14-15,21-22H,6-7H2,1H3/b4-2+,5-3-/t9-,14-,15-/m1/s1 ☒N
    Key: WYZWZEOGROVVHK-GTMNPGAYSA-N ☒N
  • InChI=1/C18H17ClO6/c1-9-6-15-14(25-15)5-3-2-4-10(20)7-11-16(18(23)24-9)12(21)8-13(22)17(11)19/h2-5,8-9,14-15,21-22H,6-7H2,1H3/b4-2+,5-3-/t9-,14-,15-/m1/s1
    Key: WYZWZEOGROVVHK-GTMNPGAYBX
  • C[C@@H]1C[C@@H]2[C@H](O2)/C=C\C=C\C(=O)Cc3c(c(cc(c3Cl)O)O)C(=O)O1
Properties
C18H17ClO6
Molar mass 364.78 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

Radicicol, also known as monorden, is a natural product that binds to Hsp90 (Heat Shock Protein 90) and alters its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis.

Biosynthesis

Biosynthesis of Radicicol has been best studied in Pochonia chlamydosporia, in which the majority of the core structure is produced in vivo through iterative type I polyketide synthases.[1] This structure produced is the earliest intermediate in the radicicol biosynthesis, monocillin II. This intermediate is transformed to radicicol through halogenation and epoxide formation performed by RadH and RadP respectively.[2] These enzymes are coded by the genes Rdc2 and Rdc4 in the pathway, and removing either of these results in a product that has the monocillin II core, but does not have either the epoxide or halogen added.[3]

Proposed biosynthetic pathway of Radicicol.

See also

Geldanamycin

References

  1. ^ Zhou H, Qiao K, Gao Z, Vederas JC, Tang Y (2010). "Insights into Radicicol Biosynthesis via Heterologous Synthesis of Intermediates and Analogs". Journal of Biological Chemistry. 285 (53): 41412–41421. doi:10.1074/jbc.M110.183574. PMC 3009867. PMID 20961859.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  2. ^ Wang, Shuhao; Xu, Yuquan; Maine, Erin A.; Wijeratne, E.M. Kithsiri; Espinosa-Artiles, Patricia; Gunatilaka, A.A. Leslie; Molnár, István (2008). "Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii". Chemistry. 15 (12): 1328–1338. doi:10.1016/j.chembiol.2008.10.006.
  3. ^ Wang, Shuhao; Xu, Yuquan; Maine, Erin A.; Wijeratne, E.M. Kithsiri; Espinosa-Artiles, Patricia; Gunatilaka, A.A. Leslie; Molnár, István (2008). "Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii". Chemistry. 15 (12): 1328–1338. doi:10.1016/j.chembiol.2008.10.006.

Further reading

  • Winssinger N, Barluanga S (January 2007). "Chemistry and biology of resorcylic acid lactones". Chem Commun. 13 (1): 22–36. doi:10.1039/B610344H. PMID 17279252. Review of the chemistry and biology of resorcylic acid lactones, including radicicol.
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