The University of Tokyo · Biochemistry, Genetics and Molecular Biology
Professor Hajime Sato's research lab specializes in the mechanistic elucidation of terpene biosynthesis, focusing on the complex carbocation cascades and rearrangements that govern the formation of structurally diverse natural products. Using a synergistic approach of computational chemistry—particularly density functional theory—and experimental techniques such as isotopic labeling, gene cluster identification, and enzyme reconstitution, the lab investigates the stereochemical and regiochemical control in terpene cyclization. Key research directions include the biosynthesis of sesterterpenes, sesquiterpenes, and meroditerpenoids, with an emphasis on understanding elusive cyclization mechanisms and the role of enzyme active sites in directing reaction pathways.
Figures are computed from collected data and may differ slightly.
Terpene cyclization is orchestrated by terpene cyclases, which are involved in the biosynthesis of various cyclic natural products, but understanding the origin and mechanism of the selectivity of terpene cyclization is challenging. In this work, we describe an in-depth mechanistic study on cyclooctatin biosynthesis by means of theoretical calculations combined with experimental methods. We show that the main framework of cyclooctatin is formed through domino-type carbocation transportation alon
Using molecular and chemotaxonomic techniques, we studied the intraspecific diversity of Oenococcus oeni, a lactic acid bacterium isolated during red wine-making in Japan. The results confirmed high values of DNA-DNA relatedness and strong similarity among 16S rDNA sequences of the isolates with the O. oeni-type strain. Pulsed-field gel electrophoresis (PFGE) by NotI identified four patterns among the strains. Three different patterns of lactate dehydrogenase mobility were seen and there was a s
The cyclization mechanisms involved in the biosynthesis of sesterterpenes are not fully understood. For example, there are two plausible reaction pathways for sesterfisherol biosynthesis, which differ in the order of ring cyclization: A-D-B/C (Path a) and A-B-C/D (Path b). It is difficult to capture intermediates of terpene cyclization, which is a complex, domino-type reaction, and so here we employed a combination of experimental and computational methods. Density functional theory calculations
The results of quantum chemical calculations on the mechanism of the carbocation cascade of reactions in the biosynthetic pathways leading to the pentacyclic sesterterpenes quiannulatene and sesterfisherol provide reasonable answers to several persistent mechanistic questions in sesterterpene biosynthesis, including: 1) the reaction pathways of the multicyclic ring system construction and skeletal rearrangements, 2) the mechanism of triquinane skeleton formation, which requires more complicated
Brasilane-type sesquiterpenes have been known for a long time, but their biosynthetic pathways and mechanisms remain elusive. Recently, two groups independently characterized a <i>Trichoderma</i> terpene cyclase that produces trichobrasilenol, a brasilane-type sesquiterpene, and a plausible biosynthetic pathway was proposed based on isotopic labeling experiments. In the proposed mechanism, the characteristic brasilane-type 5/6 bicyclic skeleton is synthesized from a 5/7/3 tricyclic intermediate
The 3(2<i>H</i>)-furanone unit is observed in many biologically active natural products, as represented by the antifungal medication griseofulvin. Setosusin (<b>1</b>) is a fungal meroditerpenoid featuring a unique spiro-fused 3(2<i>H</i>)-furanone moiety; however, the biosynthetic basis for spirofuranone formation has not been investigated since its isolation. Therefore, in this study we identified the biosynthetic gene cluster of <b>1</b> in the fungus <i>Aspergillus duricaulis</i> CBS 481.65
[Image: see text] Some experimental observations indicate that a sequential formation of secondary (2°) carbocations might be involved in some biosynthetic pathways, including those of verrucosane-type diterpenoids and mangicol-type sesterterpenoids, but it remains controversial whether or not such 2° cations are viable intermediates. Here, we performed comprehensive density functional theory calculations of these biosynthetic pathways. The results do not support previously proposed pathways/mec
Open papers in the app to read, cite, and organize with AI.
