担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cellular membranes define the physical boundary of life and provide scaffolds for various fundamental metabolic activities, including ATP synthesis, respiration, phototrophy, endocytosis and ion transport. Terpenoids, also known as isoprenoids, are known to play important roles in membrane organization and regulation across the three domains of life through unique interactions with other membrane lipids and membrane proteins. Terpenoids are present in not only the membranes of the three domains, but also viral membranes and extracellular vesicles. The large structural diversity of terpenoids and their ubiquitous distribution in modern organisms make terpenoids distinct from other membrane lipids, such as fatty acyls that are nearly absent in archaea. Addressing the biochemical and biophysical properties that allow terpenoids to play critical roles in membrane organization is important to understand the driving forces that shaped cellular life as we know it. This review summarizes the major classes of terpenoids that are involved in membrane organization and discuss the impact of terpenoid-membrane interactions on the evolutionary trajectory of membrane dynamics and the fitness of host organisms.

添付ファイル： fevo-12-1345733.pdf

DOI： 10.3389/fevo.2024.1345733

Open Access

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

添付ファイル： 1-s2.0-S0037073823001537-main.pdf

DOI： 10.1016/j.sedgeo.2023.106481

Open Access

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担当区分：筆頭著者,　責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

Terpenoids, also known as isoprenoids, are the largest and most diverse class of organic compounds in nature and are involved in many membrane-associated cellular processes, including membrane organization, electron transport chain, cell signaling, and phototrophy. Terpenoids are ancient compounds with their origin presumably before the last universal common ancestor. However, Bacteria and Archaea are known to possess two distinct terpenoid repertoires and utilize terpenoids differently. Most notably, archaea constitute their cellular membrane solely made of terpenoid-based phospholipids, contrary to the bacterial membrane that consists of fatty acid-based phospholipids. Thus, the composition of ancestral membranes at the beginning of cellular life and the diversification of terpenoids in early life remain enigmatic. This review addresses these key issues through comprehensive phylogenomic analyses of extant terpenoid biosynthesis enzymes in Bacteria and Archaea. We aim to infer the basal components of terpenoid biosynthesis machinery that have an ancient origin before the divergence of the two domains and shed light on the deep evolutionary connection between terpenoid biochemistry and early life.

添付ファイル： fuad008.pdf

DOI： 10.1093/femsre/fuad008

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その他リンク： https://academic.oup.com/femsre/article-pdf/47/2/fuad008/50971834/fuad008.pdf

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

The role of uric acid during primate evolution has remained elusive ever since it was discovered over 100 years ago that humans have unusually high levels of the small molecule in our serum. It has been difficult to generate a neutral or adaptive explanation in part because the uricase enzyme evolved to become a pseudogene in apes thus masking typical signals of sequence evolution. Adding to the difficulty is a lack of clarity on the functional role of uric acid in apes. One popular hypothesis proposes that uric acid is a potent antioxidant that increased in concentration to compensate for the lack of vitamin C synthesis in primate species ∼65 Ma. Here, we have expanded on our previous work with resurrected ancient uricase proteins to better resolve the reshaping of uricase enzymatic activity prior to ape evolution. Our results suggest that the pivotal death-knell to uricase activity occurred between 20 and 30 Ma despite small sequential modifications to its catalytic efficiency for the tens of millions of years since primates lost their ability to synthesize vitamin C, and thus the two appear uncorrelated. We also use this opportunity to demonstrate how molecular evolution can contribute to biomedicine by presenting ancient uricases to human immune cells that assay for innate reactivity against foreign antigens. A highly stable and highly catalytic ancient uricase is shown to elicit a lower immune response in more human haplotypes than other uricases currently in therapeutic development.

添付ファイル： msab312.pdf

DOI： 10.1093/molbev/msab312

Open Access

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その他リンク： https://academic.oup.com/mbe/article-pdf/39/1/msab312/42201904/msab312.pdf

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

Abstract

Glycosidases are phylogenetically widely distributed enzymes that are crucial for the cleavage of glycosidic bonds. Here, we present the exceptional properties of a putative ancestor of bacterial and eukaryotic family-1 glycosidases. The ancestral protein shares the TIM-barrel fold with its modern descendants but displays large regions with greatly enhanced conformational flexibility. Yet, the barrel core remains comparatively rigid and the ancestral glycosidase activity is stable, with an optimum temperature within the experimental range for thermophilic family-1 glycosidases. None of the ∼5500 reported crystallographic structures of ∼1400 modern glycosidases show a bound porphyrin. Remarkably, the ancestral glycosidase binds heme tightly and stoichiometrically at a well-defined buried site. Heme binding rigidifies this TIM-barrel and allosterically enhances catalysis. Our work demonstrates the capability of ancestral protein reconstructions to reveal valuable but unexpected biomolecular features when sampling distant sequence space. The potential of the ancestral glycosidase as a scaffold for custom catalysis and biosensor engineering is discussed.

添付ファイル： s41467-020-20630-1.pdf

DOI： 10.1038/s41467-020-20630-1

Open Access

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その他リンク： https://www.nature.com/articles/s41467-020-20630-1

開催年月日： 2022年5月

記述言語：英語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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開催年月日： 2022年5月

記述言語：英語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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開催年月日： 2021年10月

記述言語：英語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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開催年月日： 2021年9月

記述言語：英語   会議種別：口頭発表（基調）  

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開催年月日： 2020年5月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

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記述言語：英語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

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記述言語：日本語   会議種別：口頭発表（招待・特別）  

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記述言語：日本語   会議種別：口頭発表（一般）  

第50回討論会

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記述言語：英語   会議種別：口頭発表（一般）  

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対象： 中学生,　高校生,　保護者

種別：講演会

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対象： 小学生

種別：講演会

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対象： 中学生,　高校生,　保護者

種別：講演会

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対象： 社会人・一般,　企業

種別：講演会

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