Functional Analyses of Tyr420 and Leu607 of <i>Alicyclobacillus acidocaldarius</i> Squalene-Hopene Cyclase. Neoachillapentaene, a Novel Triterpene with the 1,5,6-Trimethylcyclohexene Moiety…

Sato, Tsutomu; Sasahara, Shigehiro; Yamakami, Toshiyuki; Hoshino, Tsutomu

doi:10.1271/bbb.66.1660

Cited by 25 publications

(24 citation statements)

References 25 publications

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“…On the other hand, the introduction of various mutations at Tyr420 in A. acidocaldarius SHC led to the production of several abortive cyclization products 6. 20…”

Section: Methodsmentioning

confidence: 99%

Enzymatic Formation of Multiple Triterpenes by Mutation of Tyrosine 510 of the Oxidosqualene‐Lanosterol Cyclase from Saccharomyces cerevisiae

Chang

2004

ChemBioChem

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Triterpene cyclases constitute a family of enzymes that catalyze diverse and complex carbocationic cyclization/rearrangement reactions of squalene and (3S)-2,3-oxidosqualene (OS) to generate a distinct array of sterols and triterpenes.[1, 2] A major determinant for the triterpenoid diversity is believed to be the precise control of conformation between substrate and enzyme, as well as the position of the carbocation intermediate formation. For example, both oxidosqualene-lanosterol cyclase (ERG7, EC 5.4.99.7) and oxidosqualene-cycloartenol synthase (CAS, EC 5.4.99.8) bind oxidosqualene in a chair-boatchair conformation, initiate and propagate cyclization to form a protosteryl cation, and then promote 1,2-shifts of hydride and methyl groups to the lanosteryl C8 cation. The lanosterol formation is accomplished through the final deprotonation, abstracting a proton originally at C9 or after a hydride shift from C9 to C8. Cycloartenol is formed after a hydride shift from C9 to C8, followed by 9b,19-cyclopropane ring closure.Elegant molecular-genetic and bioorganic investigations have recently identified several amino acid residues that are critical in probing putative active sites and determining prod- [a] Prof.

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“…On the other hand, the introduction of various mutations at Tyr420 in A. acidocaldarius SHC led to the production of several abortive cyclization products 6. 20…”

Section: Methodsmentioning

confidence: 99%

Enzymatic Formation of Multiple Triterpenes by Mutation of Tyrosine 510 of the Oxidosqualene‐Lanosterol Cyclase from Saccharomyces cerevisiae

Chang

2004

ChemBioChem

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“…We isolated 17 from the L607F, Y420A, and Y609F variants . Compound 18 is identical to the product isolated from variants I261A and F605A .…”

Section: Resultsmentioning

confidence: 90%

“…The SHC described here is from A. acidocaldarius . The cloned Escherichia coli was cultivated according to our published protocols .…”

Section: Methodsmentioning

confidence: 99%

Alicyclobacillus acidocaldarius Squalene‐Hopene Cyclase: The Critical Role of Steric Bulk at Ala306 and the First Enzymatic Synthesis of Epoxydammarane from 2,3‐Oxidosqualene

et al. 2018

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The acyclic molecule squalene (1) is cyclized into 6,6,6,6,5-fused pentacyclic hopene (2) and hopanol (3; ca. 5:1) through the action of Alicyclobacillus acidocaldarius squalene-hopene cyclase (AaSHC). The polycyclization reaction proceeds with regio- and stereochemical specificity under precise enzymatic control. This pentacyclic hopane skeleton is generated by folding 1 into an all-chair conformation. The Ala306 residue in AaSHC is conserved in known squalene-hopene cyclases (SHCs); however, increasing the steric bulk (A306T and A306V) led to the accumulation of 6,6,6,5-fused tetracyclic scaffolds possessing 20R stereochemistry in high yield (94 % for A306V). The production of the 20R configuration indicated that 1 had been folded in a chair-chair-chair-boat conformation; in contrast, the normal chair-chair-chair-chair conformation affords the tetracycle with 20S stereochemistry, but the yield produced by the A306V mutant was very low (6 %). Consequently, bulk at position 306 significantly affects the stereochemical fate during the polycyclization reaction. The SHC also accepts (3R) and (3S)-2,3-oxidosqualenes (OXSQs) to generate 3α,β-hydroxyhopenes and 3α,β-hydroxyhopanols through polycyclization initiated at the epoxide ring. However, the Val and Thr mutants generated epoxydammarane scaffolds from (3R)-OXSQ; this indicated that the polycyclization cascade started in these instances at the terminal double bond position. This work is the first to report the polycyclization of oxidosqualene starting at the terminal double bond.

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“…[20] Cases involving different cyclization conformations are rare, but this has been reported in laboratory-generated mutants of a hopene cyclase and β-amyrin cyclase. [21,22] We recently detected in Tetrahymena pyrifera small amounts of both diploptene and moretene, which arise from all-chair and Eboat cyclization, respectively (Figure 2a and c). [23]…”

Section: Triterpenols Of a Boehmerol Containing Strainmentioning

confidence: 93%

Batatasenol, a Major Triterpenol from Sweet Potato Skins

Giner

2019

Chemistry & Biodiversity

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Sweet potatoes (the tuber of Ipomoea batatas) are a major food crop globally. The sweet potato weevil (Cylas formicarius elegantulus) is a serious pest of this important crop. The triterpenol, boehmerol, has previously been found in the skin of the tuber where, as its acetate ester, it has been shown to signal oviposition by the weevil. A new triterpenol, batatasenol, was identified in two varieties of sweet potatoes, ‘Covington’ and ‘Purple Stokes’. In the ‘Covington’ variety, batatasenol was practically the only triterpenol present in the skins. In the ‘Purple Stokes’ variety, batatasenol was present along with boehmerol and several minor triterpenols. Based on the structures of the co‐occurring compounds, it is proposed that their biosynthesis involves an epoxysqualene cyclase which can carry out both all‐chair and B‐boat cyclizations.

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Functional Analyses of Tyr420 and Leu607 of Alicyclobacillus acidocaldarius Squalene-Hopene Cyclase. Neoachillapentaene, a Novel Triterpene with the 1,5,6-Trimethylcyclohexene Moiety…

Cited by 25 publications

References 25 publications

Enzymatic Formation of Multiple Triterpenes by Mutation of Tyrosine 510 of the Oxidosqualene‐Lanosterol Cyclase from Saccharomyces cerevisiae

Enzymatic Formation of Multiple Triterpenes by Mutation of Tyrosine 510 of the Oxidosqualene‐Lanosterol Cyclase from Saccharomyces cerevisiae

Alicyclobacillus acidocaldarius Squalene‐Hopene Cyclase: The Critical Role of Steric Bulk at Ala306 and the First Enzymatic Synthesis of Epoxydammarane from 2,3‐Oxidosqualene

Batatasenol, a Major Triterpenol from Sweet Potato Skins

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