Structural highlights
Function
5EAS_TOBAC Catalyzes the cyclization of trans,trans-farnesyl diphosphate (FPP) to the bicyclic intermediate 5-epi-aristolochene, initial step in the conversion of FPP to the sesquiterpenoid antifungal phytoalexin capsidiol. Produces germacrene A as an enzyme-bound intermediate that is not released by the enzyme, but is further cyclized to produce the bicyclic 5-epi-aristolochene.
Publication Abstract from PubMed
As part of an effort to identify substrate analogs suitable for helping to resolve structural features important for terpene synthases, the inhibition of 5-epi-aristolochene biosynthesis from farnesyl diphosphate (FPP) by the tobacco 5-epi-aristolochene synthase incubated with anilinogeranyl diphosphate (AGPP) was examined. The apparent noncompetitive nature of the inhibition supported further assessment of how AGPP might be bound to crystallographic forms of the enzyme. Surprisingly, the bound form of the inhibitor appeared to have undergone a cyclization event consistent with the native mechanism associated with FPP catalysis. Biocatalytic formation of a novel 13-membered macrocyclic paracyclophane alkaloid was confirmed by high-resolution GC-MS and NMR analysis. This work provides insights into new biosynthetic means for generating novel, functionally diversified, medium-sized terpene alkaloids.
Formation of a Novel Macrocyclic Alkaloid from the Unnatural Farnesyl Diphosphate Analogue Anilinogeranyl Diphosphate by 5-Epi-Aristolochene Synthase.,Rising KA, Crenshaw CM, Koo HJ, Subramanian T, Chehade KA, Starks C, Allen KD, Andres DA, Spielmann HP, Noel JP, Chappell J ACS Chem Biol. 2015 May 4. PMID:25897591[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Rising KA, Crenshaw CM, Koo HJ, Subramanian T, Chehade KA, Starks C, Allen KD, Andres DA, Spielmann HP, Noel JP, Chappell J. Formation of a Novel Macrocyclic Alkaloid from the Unnatural Farnesyl Diphosphate Analogue Anilinogeranyl Diphosphate by 5-Epi-Aristolochene Synthase. ACS Chem Biol. 2015 May 4. PMID:25897591 doi:http://dx.doi.org/10.1021/acschembio.5b00145
