Synthesis of Deuterated Mevalonolactone Isotopomers

Dickschat, Jeroen S.; Citron, Christian A.; Brock, Nelson L.; Riclea, Ramona; Kuhz, Henning

doi:10.1002/ejoc.201100188

Cited by 24 publications

(17 citation statements)

References 25 publications

(9 reference statements)

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“…All diterpenes can be generated via cation 21 from GGPP in the chair-chair-or (as discussed above) in the boat-chair-"antipodal" fold. Deprotonation of 21 or capture by water can result in ent-copalyl diphosphate (4) on the main pathway (bold arrows), or the side product labda-13-en-8-ol-15-yl diphosphate (22), respectively. Both CPS products can be accepted by the KS domain to abstract the diphosphate moiety, thereby yielding cations 23 or 25.…”

Section: Diterpenes From Fusarium Fujikuroi Imi58289mentioning

confidence: 99%

“…To discriminate between the two methyl groups, [6,6, H 3 ]-mevalonolactone (MVA) was synthesised according to a recently developed flexible procedure for the preparation of deuterated MVA isotopomers, and used in feeding experiments. [22] [6,6,6-2 H 3 ]MVA is biotransformed to [ 2 H 12 ]GGPP with specific deuterium labelling of the terminal Z methyl group and the three internal methyl groups. [23] Of these twelve deuteriums, one is lost during the cyclisation to ent-CPP (4) and another in the transformation of 4 to ent-kaurene; accordingly, the incorporation of up to ten deuterium atoms into 5 was found as indicated by a shift of the molecular ion from m/z 272 to m/z 282.…”

Section: Diterpenes From Fusarium Fujikuroi Mutant Strainsmentioning

confidence: 99%

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Biosynthesis of Sesqui‐ and Diterpenes by the Gibberellin Producer Fusarium fujikuroi

Brock¹,

Tudzynski²,

Dickschat³

2011

ChemBioChem

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The fungus Fusarium fujikuroi IMI58289 emits a complex pattern of volatile terpenoids including two major compounds, the sesquiterpene alcohol α-acorenol and the diterpene ent-kaurene. ent-Kaurene is the precursor for the phytohormone gibberellic acid (GA(3)) and is produced from geranylgeranyl diphosphate (GGPP) via ent-copalyl diphosphate by the bifunctional ent-copalyl diphosphate/ent-kaurene synthase (CPS/KS). Several structurally related diterpenes were identified as side products of the CPS/KS. Deletion of the cps/ks gene or the whole GA(3) biosynthetic gene cluster resulted in completely abolished diterpene production. Mutants with deletions of the cytochrome P450 monooxygenase gene P450-4, which is responsible for the three oxidation steps from ent-kaurene to ent-kaurenoic acid en route to GA(3), accumulate diterpene hydrocarbons. Feeding with [6,6,6-(2) H(3)] mevalonolactone gave insights into the stereochemistry of the GGPP cyclisation, which operates with a chair-chair-"antipodal" fold. A rational biosynthetic scheme for all identified sesquiterpenes demonstrated their formation from farnesyl diphosphate (FPP) via three alternative initial cyclisations. Genome sequencing revealed the presence of five putative sesquiterpene synthase genes in the F. fujikuroi genome. The structures of several trace compounds from other classes have been identified as new natural products; these were delineated from their mass spectra and unambiguously assigned by comparison to synthetic references.

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Section: Diterpenes From Fusarium Fujikuroi Imi58289mentioning

confidence: 99%

Section: Diterpenes From Fusarium Fujikuroi Mutant Strainsmentioning

confidence: 99%

Biosynthesis of Sesqui‐ and Diterpenes by the Gibberellin Producer Fusarium fujikuroi

Brock¹,

Tudzynski²,

Dickschat³

2011

ChemBioChem

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“…Further interesting insights into the biosynthesis of trichodiene were obtained in feeding experiments with isotopically labelled [6,6, [27] The deuterium label was incorporated into specific positions of 3 (Scheme 10) resulting in the mass spectra displayed in Figure S6 in the Supporting Information. Pure mass spectra of the deuterated iso- topomers were obtained because they elute with shorter GC retention times than their unlabelled pendants.…”

mentioning

confidence: 99%

Biosynthesis of Sesquiterpenes by the Fungus Fusarium verticillioides

et al. 2011

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The volatiles of the fungus Fusarium verticillioides were analysed by GC-MS. Sesquiterpenes dominated, with trichodiene as the principle component. Several other sesquiterpenes were detected in low amounts that were unambiguously identified from their mass spectra and retention indices. The absolute configurations of (R)-β-bisabolene, (R)-cuparene, (+)-β-barbatene, (-)-α-cedrene, (+)-β-cedrene, and (+)-α-funebrene originating from different key cationic intermediates, were determined by chiral GC-MS and proved to be related to the trichodiene stereostructure. The unusual compound (E)-iso-γ-bisabolene was also found corroborating a previously suggested mechanism for the cyclisation of the bisabolyl to the cuprenyl cation that is based on quantum mechanical calculations (Y. J. Hong, D. J. Tantillo, Org. Lett. 2006, 8, 4601-4604). These analyses resulted in a revised biosynthesis scheme to trichodiene and the side products of the responsible terpene cyclase, trichodiene synthase, an enzyme that is well characterised from Fusarium sporotrichioides. Feeding studies with several deuterated mevalonolactone isotopomers unravelled stereochemical aspects of the late cyclisations towards trichodiene.

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“…This finding suggested that the conformation of intermediate cation A was strictly controlled by the enzyme,a llowing no rotation of the C1-16-17 group prior to further cyclization to B, and was in line with similar resultso btained for various other terpenes,i ncluding 2-methylisoborneol,h ypodoratoxide, and pentalenolactone. [22] The biosynthesis of 4 was furthers tudied by feeding of deuterated mevalonolactones [23] and analysiso ft he incorporation and fragment ions by GC/MS. [22] The biosynthesis of 4 was furthers tudied by feeding of deuterated mevalonolactones [23] and analysiso ft he incorporation and fragment ions by GC/MS.…”

Section: Resultsmentioning

confidence: 99%

Harzianone Biosynthesis by the Biocontrol Fungus Trichoderma

Barra

Dickschat

2017

ChemBioChem

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Analysis of the volatile terpenes produced by seven fungal strains of the genus Trichoderma by use of a closed-loop stripping apparatus (CLSA) revealed a common production of harzianone, a bioactive, structurally unique diterpenoid consisting of a fused tetracyclic 4,7,5,6-membered ring system. The terpene cyclization mechanism was studied by feeding experiments using selectively C- and H-labeled synthetic mevalonolactone isotopologues, followed by analysis of the incorporation patterns by C NMR spectroscopy and GC/MS. The structure of harzianone was further supported from a C, C COSY experiment of the in-vivo-generated fully C-labeled diterpene.

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Synthesis of Deuterated Mevalonolactone Isotopomers

Cited by 24 publications

References 25 publications

Biosynthesis of Sesqui‐ and Diterpenes by the Gibberellin Producer Fusarium fujikuroi

Biosynthesis of Sesqui‐ and Diterpenes by the Gibberellin Producer Fusarium fujikuroi

Biosynthesis of Sesquiterpenes by the Fungus Fusarium verticillioides

Harzianone Biosynthesis by the Biocontrol Fungus Trichoderma

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