有用油脂を生産する微生物のゲノム育種とその健康食品、化粧品、医薬品、化学品やバイオエネルギー供給への応用 展開をめざした研究を行っています。 

We are conducting research aimed at genome breeding of microorganisms that produce useful fats and oils and their application to the fields of health foods, health care materials, cosmetics, pharmaceuticals, chemicals, and bioenergy. 

keywords： Biorefinery, Biomass, Carbon recycle, Enzyme, Lipid, Microorganism 

1. Improvement of fatty acid productivity of thraustochytrid, Aurantiochytrium sp. by genome editing. J. Biosci. Bioeng., 131, 373-380 （2021） 
2. Metabolite profile analysis of Aurantiochytrium limacinum SR21 grown on acetate-based medium for lipid fermentation. J. Oleo Sci., 68, 541-549 （2019） 
3. Isolation of high carotenoid-producing Aurantiochytrium sp. mutants and improvement of astaxanthin productivity using metabolic information. J. Oleo Sci., 67, 571-578 （2018）

放線菌は、多くの有用な抗生物質（二次代謝産物）を生産する。生化学・有機化学・分子生物学を駆使して、抗生物質の 生合成遺伝子群を解析・操作し、新規抗生物質の創製や生産制御機構の解明などを目指している。 

Actinobacteria produces a wide variety of valuable secondary metabolites including antibiotics. Our group focuses on creation of novel bioactive compounds through genetic engineering of their biosynthetic and regulatory genes, using biochemistry, organic chemistry, and molecular biology. 

keywords： Biosynthesis, Regulatory gene, Secondary metabolite, Antibiotic, Actinobacteria 

1. Functional analysis of P450 monooxygenase SrrO in the biosynthesis of butenolide-type signaling molecules in Streptomyces rochei. Biomolecules, 10, 1237 （2020）. 
2. SrrB, a pseudo-receptor protein, acts as a negative regulator for lankacidin and lankamycin production in Streptomyces rochei. Front. Microbiol., 11, 1089 （2020）. 
3. The genome sequence of Streptomyces rochei 7434AN4, which carries a linear chromosome and three characteristic linear plasmids. Sci. Rep., 9, 10973 （2019）.

海洋細菌の多様性と高機能性に注目し、その有用遺伝子利用のための画期的な遺伝子検出技術・遺伝子合成技術を 開発した。また、生物機能を利用して、廃棄物から金属結晶合成やバイオプラスチック原料生産も行っている。 

We have focused on the diversity and high functionality of marine bacteria, and developed innovative gene detection and gene synthesis technologies in order to utilize their useful genes. In addition, we have studied on metal mineralization, production of biopolymers and chemical building blocks using wastewater and biomass through bioconversion process. 

keywords： marine bacteria, RHa-RCA, gene synthesis technology, metal mineralization, biopolymers, chemical building blocks 

1. Development of a transformation system for Nitratireductor sp. Marine Biotechnology, （2023）
2. Screening of Neutrophil Activating Factors from a Metagenome Library of Sponge-Associated Bacteria. Mar. Drugs, 19, 427. （2021） 
3. Direct detection of mRNA expression in microbial cells by fluorescence in situ hybridization using RNase H-assisted rolling circle amplification. Sci.c Rep., 10, 9588. （2020）

微生物の優れた生物機能を活用して汚染環境の浄化や、農薬・肥料をなるべく使用しない環境適合型農業の確立を図 る環境バイオテクノロジーの研究を行っている。今注目している生物機能は微生物の物質認識機構である。 

I am interested in superior biofunctions and their application to environmental biotechnology and bioproduction of value-added chemicals. I am paying special attention to molecular recognition mechanism of environmental bacteria and its application to establishment of sustainable agriculture. 

keywords： environmental biotechnology, applied microbiology, microbe-plant interaction, bioproduction 

1. Characterization of methyl-accepting chemotaxis proteins （MCPs） for amino acids in plant-growth-promoting rhizobacterium Pseudomonas protegens CHA0 and enhancement of amino acid chemotaxis by MCP genes overexpression. Biosci. Biotechnol. Biochem. 84:1948-1957 （2020）. 
2. Identification of boric acid as a novel chemoattractant and elucidation of its chemoreceptor in Ralstonia pseudosolanacearum Ps29. Sci. Rep. 7:8609 （2017）. 
3. Identification of the mcpA and mcpM Genes, Encoding Methyl-Accepting Proteins Involved in Amino Acid and l-Malate Chemotaxis, and Involvement of McpM-Mediated Chemotaxis in Plant Infection by Ralstonia pseudosolanacearum（Formerly Ralstonia solanacearum Phylotypes I and III）. Appl. Environ. Microbiol. 81:7420-7430 （2015）.

健康と医療のバイオテクノロジー：アレルギー発症機構解明と創薬分子標的探索/食と免疫による加齢難病制御 

My lab focuses on healthcare biotechnology. Ongoing projects are: 1） Immune regulation of age-related disorders, 2） Development of diagnostics and immunotherapeutics for allergy, and 3） Prevention of proinflammatory disorders by food factors. 

keywords： allergy, food factors, healthcare biotechnology, immunology 

1. Influences of maternal factors over offspring allergies and the application for food allergy. Front. Immunol. 10, 1933 （2019） 
2. Der f 35: an MD-2-like house dust mite allergen that cross-reacts with Der f 2 and Pso o 2. Allergy 72, 1728 （2017） 
3. Der f 34, a novel major house dust mite allergen belonging to a highly conserved Rid/YjgF/YER057c/UK114 family of imine deaminases. J. Biol. Chem. 291, 21607 （2016

無機固体や有機固体など様々な界面と結合するペプチドを選択し、応用すること。具体的にはアスベスト検査やエクソソームの単離、半導体バイオセンサーへ展開している。 

Creation of new proteins/peptides that bind to inorganic/organic surfaces by evolutionary molecular engineering. For example, we created an asbestos-binding protein and applied it to asbestos detection （biosensing） in environments. We also created a membrane-binding peptide in order to isolate extracellular membrane vesicle （exosome, microvesicles）. 

keywords： Protein engineering, Evolutionary molecular engineering, Inorganic/organic surfaces, Biosensing, Asbestos, Exosome, Microvesicles 

1. Application of peptides with an affinity for phospholipid membranes during the automated purification of extracellular vesicles, Sci. Rep., 10, 18718 （2020） 
2. Live-cell imaging of macrophage phagocytosis of asbestos fibers under fluorescence microscopy, Genes Env., 41, 14-25 （2019） 
3. Rapid on-site detection of airborne asbestos fibers and potentially hazardous nanomaterials using fluorescence microscopy-based biosensing, Biotechnol J. 11, 757-767 （2016）

カーボンリサイクル社会の実現を目指し、ライフサイクルアセスメントに基づく研究計画を策定し、再生可能資源、および 再生可能エネルギーと二酸化炭素を基質とするバイオリファイナリープロセスを開発しています。 

Aiming to realize a carbon recycling society, we make research plans based on life cycle assessment and developing several biorefinery processes using biomass, renewable energy and carbon dioxide. 

keywords： carbon recycling society, biorefinery, renewable energy 

1. Thermophilic ethanol fermentation from lignocellulose hydrolysate by genetically engineered Moorella thermoacetica/Bioresour. Technol./2017 
2. Semi-continuous methane production from undiluted brown algae using a halophilic marine microbial community/Bioresour. Technol./2016 
3. Improved methane fermentation of chicken manure via ammonia removal by biogas recycle/Bioresour. Technol./2010

生命の必須元素である「リン」の代謝メカニズムと、その生物循環における役割を研究している。また、これらの知見を、 リン資源の有効活用、効率的な物質生産やバイオセーフティ技術に応用する研究も展開している。 

We are interested in the phosphorus metabolism of microorganisms and their contribution to global phosphorus cycling in terrestrial and aquatic environments. Based on the obtained knowledge in combination with synthetic biology, we are developing novel environmental biotechnologies for phosphorous resource management and bacterial cell growth control for biosafety measures. 

keywords： phosphate, phosphorous cycling, bacteria, cyanobacteria, environmental biotechnology, synthetic biology, biosafety 

1. Synthetic phosphorus metabolic pathway for biosafety and contamination management of cyanobacterial cultivation. ACS Synth. Biol. 7（9）: 2189-2198 （2018） 
2. A novel biocontainment strategy makes bacterial growth and survival dependent on phosphite. Sci. Rep. 7:44748 （2017） 
3. Bacterial phosphate metabolism and its application to phosphorus recovery and industrial bioprocesses. J. Biosci. Bioeng. 109:423-432 （2010）

モデル生物（酵母と線虫）を用いて寿命メカニズムの解明に取り組んでいる。特に、代謝産物による老化防止、健康長 寿に着目し、その成果を、医薬のみならず食品分野へと応用展開させることを目的としている。 

Using model organisms （yeast and nematode）, we are elucidating the mechanism of lifespan. In particular, we focus on the prevention of aging and healthy longevity by metabolites, and aim to apply them not only to medicine but also to the food field. 

keywords： S. cerevisiae, C. elegans, aging, lifespan 

1. Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK. Proc. Natl. Acad. Sci. USA （2016） 
2. mTORC2-SGK-1 acts in two environmentally responsive pathways with opposing effects on longevity. Aging Cell （2014） 
3. Role of calcineurin and Mpk1 in regulating the onset of mitosis in budding yeast. Nature （1998）

難培養・未培養微生物の理解・利用を目指して、革新的な分離培養手法の開発と未知増殖制御機構（培養できない理 由）の解明に取り組んでいます。得られた成果の医薬・環境など幅広い分野への応用展開も図っています。 

Most microorganisms in nature are not readily cultivable in the laboratory. This is the biggest impediment for understanding and application of environmental microorganisms. My research focuses on 1） innovations for microbial cultivation, 2） cultivation of uncultivated microorganisms, and 3） puzzling out the mechanism for "microbial uncultivability" of environmental microorganisms. 

keywords： uncultivable microorganisms, isolation, microbial dormancy, growth controling network 

1. Isolation of sublineage I Nitrospira by a novel cultivation strategy/Environ. Microbiol./2014 
2. In Situ Cultivation Allows for Recovery of Bacterial Types Competitive in Their Natural Environment/Microb. Environ./2016 
3. Isolation of Microorganisms Using Sub-Micrometer Constrictions/PLOS One/ 2014

無機固体であるシリカ（SiO₂）を細胞内で形成する細菌を発見し、そのメカニズムの解析を進めている。生物のシリカ形成 機構を解明し、新たなバイオ融合マテリアル開発に応用することを目指している。 

My current research focuses on bacterial biosilicification （silica biomineralization）, the biological process through which soluble silicic acid, Si（OH）₄, is polymerized intracellularly and deposited as insoluble silica, SiO₂. I am also working for the development of new biomaterials by integrating biomolecules with silicon-based materials （including semiconductor devices）. 

keywords： biosilicification, biomaterial fabrication, silica 

1. Bacterial biosilicification: a new insight into the global silicon cycle. Biosci Biotechnol Biochem 85: 1324-1331 （2021） 
2. Application of volcanic ash particles for protein affinity purification with a minimized silica-binding tag. J Biosci Bioeng 122: 633-638 （2016） 
3. The C-terminal zwitterionic sequence of CotB1 is essential for biosilicification of the Bacillus cereus spore coat. J Bacteriol 198: 276-282 （2016）

微生物細胞はどのようにして生存のための恒常性を維持し、そしてどのような過程を経て死滅するのでしょうか。細胞の生と死の境界がどこにあるのかを知るため、1細胞観察と定量解析を組み合わせて研究しています。 

How do microbial cells maintain cellular homeostasis for proliferation? Which kind of processes do they go through when they die? We aim to clarify the boundary of life and death and find the principles of life. These findings will help us to create useful host cells for bioprocess. 

keywords： Microbial cells, single-cell observation 

1. A constant size extension drives bacterial cell size homeostasis., Cell, 159: 1433-1446, 2014 
2. Spatial self-organization resolves conflicts between individuality and collective migration., Nat Commun., 9:2177, 2018 
3. Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators., eLife, 6: e28842, 2017

アミノ酸・オリゴペプチドによる微生物（酵母）の生理機能調節について、１）細胞膜輸送体の発現・活性制御や基質特 異性の研究、２）増殖阻害など新規生理作用探索とその作用機構の解明、を調べています。 

We investigate how amino acids and oligopeptides regulate physiological function of yeast cells; 1） regulation of amino acid/peptide transporter expression, 2） exploration of novel substrate of transporters, 3） unidentified physiological action of amino acids/dipeptides（e.g. growth inhibition） and its mechanism. 

keywords：yeast, amino acid, oligopeptide, transporter, growth inhibtion 

1. Critical role of the proton-dependent oligopeptide transporter （POT） in the cellular uptake of the peptidyl nucleoside antibiotic, blasticidin S. Biochim Biophys Acta Mol Cell Res 1864: 393 （2017） 
2. Identification of ubiquitin-proteasome system components affecting the degradation of the transcription factor Pap1. Redox Biol 28: 101305 （2020） 
3. Inhibition of the Arg/N-end rule pathway-mediated proteolysis by dipeptide-mimetic molecules. Amino Acids 48: 235 （2016）

バイオ変換を効率的に行うシンプル酵素触媒を開発している。中温性酵素を発現させた低温菌を中温で熱処理すること で宿主の競合反応を抑え、有用物質が高生産される。これまでにポリマー素材の高収率生産を実現した。 

My research interest is bioconversion using various kinds of enzymes. We have developed psychrophile-based simple biocatalysts（PSCats）to conduct efficient conversions. PSCats can produce the valuable compounds with high yields only by thermostable enzymes, which are heterologously expressed in psychrophilic cells whose metabolism is suppressed by heat treatment. 

keywords： Efficient bioconversion, Simple biocatalyst, Psychrophilic bacteria 

1. Unexpectedly high thermostability of an NADP-dependent malic enzyme from a psychrophilic bacterium, Shewanella livingstonensis Ac10, J Biosci Bioeng, 132:445-450（2021） 
2. Accelerating itaconic acid production by increasing membrane permeability of whole-cell biocatalyst based on a psychrophilic bacterium Shewanella livingstonensis Ac10, J Biotechnol, 312:56-62（2020） 
3. Efficient production of 1,3-propanediol by psychrophile-based simple biocatalysts in Shewanella livingstonensis Ac10 and Shewanella frigidimarina DSM 12253, J Biotechnol, 323:293-301（2020）

タンパク質翻訳後修飾の1つである糖鎖付加は、細菌やウイルスなどの病原体の感染、癌化、薬物耐性獲得などに関 わっている。これらの生物学的な機序を質量分析装置などを用いた糖鎖構造解析法により解明する。 

Glycosylation, which is one of the posttranslational modifications of proteins, is involved in infection by pathogens such as bacteria and viruses, cancer and acquisition of drug-resistance. We investigate these biological mechanisms with detailed analysis of glycan structures by mass spectrometry. 

keywords： glycan, mass spectromery, biomarker 

1. Structural analysis of the GPI glycan. PLoS One. 16 （9） :e0257435 （2021） 
2. Human Dectin-1 is O-glycosylated and serves as a ligand for C-type lectin receptor CLEC-2. Elife 11: e83037 （2022） 
3. Examination of differential glycoprotein preferences of N-acetylglucosaminyltransferase-IV isozymes a and b. J Biol Chem. 298 :102400 （2022）

バクテリアやファージ等の微生物と植物の相互作用の研究を行い、病害防除への応用を目指しています。また、有用物質 を生産するために、微細藻類のゲノム編集技術を開発しています。 

We are studying the interaction of microorganisms, such as bacteria and phages, with plants, with the aim of applying them to disease control. We are also developing genome editing technology for algae to produce useful substances, such as biodiesel or EPA. 

keywords： algae, microorgnisms, biodiesel, genome-editing 

1. Zepp, a LINE-like retrotransposon accumulated in the Chlorella telomeric region. EMBO J. 16:3715-3723. （1997） 
2. The involvement of a cysteine proteinase in the nodule development in Chinese milk vetch infected with Mesorhizobium huakuii subsp. rengei. Plant Physiology.124: 1087-1095. （2000） 
3. Monitoring growth and movement of Ralstonia solanacearum cells harboring plasmid pRSS12 derived from bacteriophage φRSS1. J. Biosci. Bioeng., 109. 153 – 158. （2010）

生体分子や生細胞を機能性材料として捉え、バイオデバイスとしての活用法を開拓する。タンパク質、核酸などを利用 したバイオセンシング分子開発や、生細胞応答測定法、生細胞機能制御法の開発などを行っている。 

Our research focuses on the utilization of biomolecules and living cells as functional materials to create biodevices. We are developing novel functional molecules such as biosensing molecules with proteins or nucleic acids. We are also exploring new methods to create, evaluate, and manipulate functional living cells. 

keywords： Biodevices, Biosensing molecules, Cellular devices 

1. Insulin sensor cells for the analysis of insulin secretion responses in single living pancreatic β cells, Analyst, 144, 3765-3772, 2019 
2. Continuous monitoring of specific mRNA expression responses with a FRET-based DNA nano-tweezer technique that does not require gene recombination, Analytical Chemistry, 88, 7894-7898, 2016 
3. A split G-quadruplex-based DNA nano-tweezers structure as a signal-transducing molecule for the homogeneous detection of specific nucleic acids, Biosensors & Bioelectronics, 74, 222-226, 2015

生体分子（ペプチドなど）と固体表面との界面を制御して、バイオと異分野を繋ぐ研究を進めている。脂質二重層という有 機的界面とペプチドとの相互作用を利用し、エクソソームの精製技術の開発や研究を行っている。 

My research connects biotechnology and different fields using biomolecules that interact with the surface of inorganic （asbestos） or organic （lipid bilayer）. Recently, we are developing peptides that bind to the lipid bilayer of exosomes, which has the potential to be used in regenerative medicine, and applied it to exosome purification. 

keywords： Peptides, Binding peptides, Asbestos, Exosome 

1. Application of peptides with an affinity for phospholipid membranes during the automated purification of extracellular vesicles. Sci Rep . 10:18718 （2020） 
2. Live-cell imaging of macrophage phagocytosis of asbestos fibers under fluorescence microscopy. Genes Environ. 41:14 （2019） 
3. Rapid on-site detection of airborne asbestos fibers and potentially hazardous nanomaterials using fluorescence microscopy-based biosensing. Biotechnol J . 11:757 （2016）

モデル生物の酵母や線虫を用いて、①栄養応答経路が制御する細胞成長・代謝・ストレス抵抗性、および②老化によっ て栄養応答性が破綻するメカニズム、を研究し、老化における栄養応答機能の役割の解明を目指している。 

Using yeast S. cerevisiae and nematode C. elegans, I study the functions regulated by nutrient signaling, such as cell growth, metabolism, and stress resistance, as well as the mechanisms by which nutrient responsiveness declines with aging, aiming to gain insights into the significance of nutrient sensing mechanism during aging. 

keywords： Yeast, Nematode, Aging, Growth, Metabolism, Nutrient sensing 

1. S‐adenosyl‐L‐homocysteine extends lifespan through methionine restriction effects. Aging Cell 21: e13604 （2022） 
2. Stimulating S-adenosyl-l-methionine synthesis extends lifespan via activation of AMPK. Proceedings of the National Academy of Sciences 113: 11913-11918 （2016） 
3. Ras/cAMP-dependent Protein Kinase （PKA） Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast. Journal of Biological Chemistry 288: 10558-10566 （2013）

環境中での細菌の挙動（病原菌の植物感染など）を制御するために、細菌運動性における物質認識に着目している。病 原菌が植物根から分泌される特定の物質を目印にして植物体を探索し移動することを見出してきた。 

Studies on mechanism of chemical recognition involved in directional motility of environmental bacteria and its roles in biological interactions such as infection and symbiosis, and its applications to biotechnology. 

keywords： bacteria, motility, plant pathogen 

1. Chemotactic disruption as a method to control bacterial wilt caused by Ralstonia pseudosolanacearum. Biosci Biotech Biochem （2020） 
2. Identification of boric acid as a novel chemoattractant and elucidation of its chemoreceptor in Ralstonia pseudosolanacearum Ps29. Sci Rep （2017） 
3. Identification of the mcpA and mcpM genes, encoding methyl-accepting proteins involved in amino acid and L-malate chemotaxis, and involvement of McpM-mediated chemotaxis in plant infection by Ralstonia pseudosolanacearum（formerly Ralstonia solanacearum phylotype I and III）. App Environ Microbiol （2015）

植物は様々な環境変化に対して体の成長や生理機能を柔軟に変化させて応答する。環境応答の仕組みを分子レベルで 理解し，応用展開を図って，私たちの社会や環境に役立てる研究を目指している。 

Plants respond to shifting environmental conditions by changing their growth, development, and physiology. Our goal is to decipher its molecular underpinnings and to harness the power of plants for the good of society and environment. 

keywords： Plants, cell differentiation, intercellular signaling, molecular evolution, RNA modifications, signaling peptides 

1. The sequenced genomes of non-flowering land plants reveal the innovative evolutionary history of peptide signaling. Plant Cell. 33: 2915- 2934 （2021） 
2. Antagonistic roles for KNOX1 and KNOX2 genes in patterning the land plant body plan following an ancient gene duplication. PLoS Genet. 11: e1004980 （2015） 
3. Active suppression of a leaf meristem orchestrates determinate leaf growth. eLife. 5. pii: e15023 （2016）