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Seminar on Green Sustainable Chemistry in Tottori (2012-2)

 

日時：2012年12月3日（月）   13時より〜16時00分  

場所：鳥取大学大学院工学研究科大講義室  

鳥取市湖山町南4-101  

主催  

 

鳥取大学工学部附属グリーン・サスティナブル・ケミストリー(GSC)

研究センター   (学長裁量経費：持続性社会構築のための基盤科学の国

際研究拠点を担う人材育成   )  

 

 

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プログラム  

 

開会  

 

13:00-14:  00:  座長   伊藤  敏幸  

Franz  Hollmann  (オランダ，Delft  工科大学)    

「Oxidoreductases  for  a  greener  organic  synthesis  –  scope  

and  challenges」  

 

14:00-15:00：座長   簗瀬  英司  

伊藤   伸哉（富山県立大学教授，生物工学研究センター所長）  

「Development   of   novel   biocatalysts   for   producing   chiral  

compounds」  

 

15:10-15:40：座長   櫻井  敏彦  

溝端   知宏（鳥取大学大学院工学研究科  准教授）  

「Elucidating  the  molecular  mechanism  of  chaperonin-  

facilitated  protein  folding」  

 

閉会  

 

 

   

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Frank Hollmann Frank Hollmann was born in Koblenz, Germany in 1973. He studied Chemistry at the university of Bonn, Germany where he completed his MSc studies with Prof. Eberhard Steckhan in the field of bioelectrochemistry. After Prof. Steckhans death, Frank continued his PhD project on electrochemical cofactor regeneration with Prof. Andreas Schmid at the Swiss Federal Institute of Technology (ETH) in Zurich, Switzerland. In 2004, he joined the group of Prof. Manfred Reetz at the Max-Planck-Institute for Coal Reseach in Muelheim, Germany to contribute to Prof. Reetz’ efforts in design and evolution of artificial hybrid catalysts. Between 2005 and 2008, Frank gathered some industrial experience as R&D manager at Evonik Industries (formerly Degussa Goldschmidt) in the Care and Surface Specialties Business Unit. Since April 2008, Frank holds an Assistant Professorship in the Department of Biotechnology at the Delft University of Technology in Delft (The Netherlands). His research interest centre around the application of redox enzymes for organic synthesis. One facet of this research is to develop new regeneration systems for oxidoreductases to supply these enzymes with the redox equivalents needed for catalysis. This comprises NAD(P)-independent regeneration systems and the use of tailored synthetic NAD-model compounds. Another important concern is the evaluation of the environmental impact of the (biocatalytic) production system. From an environmental point of view biocatalysis is not per se greener then ‘traditional’ chemical methods and common myths have to be dispelled by facts. Frank Hollmann has co-authored 50 scientific papers, 5 book chapters and holds 5 patents. He collaborates heavily with partners from the European Union, The United States and South Africa. And hopefully Japan soon…

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Oxidoreductases for a greener organic synthesis – scope and challenges

Frank Hollmann

Delft University of Technology, The Netherlands

E-mail: F.Hollmann@tudelft.nl

Biocatalysis has a good reputation as being greener than traditional chemocatalysis. Often, mild reaction conditions and aqueous reaction conditions are mentioned as the key arguments to underline the environmental benignity of biocatalysis. But is that always true? Unfortunately, only few publications quantify the environmental impact of a given (bio)catalytic transformation. In this presentation I will try to outline and evaluate crucial parameters to judge on the environmental benignity of a given reaction and how to identify bottlenecks. As tool I will propose the Environmental Assessment Tool for Organic Synthesis (EATOS).[1]

The model enzyme class discussed in this presentation will be oxidoreductases. The enzymes catalyse a range of very interesting reactions not accessible with state-of-the-art chemical catalysis; making them valuable tools for organic synthesis. Not very astonishingly thus, they have been in focus of academic and industrial research for more than two decades now.[2] Nevertheless, there is still room for discovery of unprecedented activities and novel possibilities. Some of the recent developments will be discussed. [1] M. Eissen, J. O. Metzger, Chem.-Eur. J. 2002, 8, 3580-3585. [2] a) F. Hollmann, I. W. C. E. Arends, D. Holtmann, Green Chem. 2011, 13, 2285–

2313; b) F. Hollmann, I. W. C. E. Arends, K. Buehler, A. Schallmey, B. Buhler, Green Chem. 2011, 13, 226-265.

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Nobuya Itoh

Nobuya Itoh was born in Suzuka, Mie, Japan, in 1955. He studied applied chemistry with a focus on biocatalysts under Professor Saburo Fukui at Kyoto University, Faculty of Engineering, and completed the Bachelor's and Master's program. During the researcher of Amano Enzyme Co. at Nagoya, he got a chance to study under Prof. Hideaki Yamada, at Kyoto University, Faculty of Agriculture, and obtained Ph. D. from the Graduate School of Agriculture, Kyoto University, in 1988. The title of his Ph.D. thesis is “Studies on the halogenation reactions catalyzed by the haloperoxidases from Caldariomyces fumago and Corallina pilulifera In 1989, he accepted the position of Lecturer, Faculty of Engineering, at Fukui University, and was promoted to Associate Professor at the same University in 1991. He won Japan Society for Bioscience, Biotechnology, and Agrochemistry Award for the Encouragement of Young Scientists in 1995. In 1997, he accepted the position of Professor, Biotechnology Research Center and Department of Biotechnology, Faculty of Engineering, at Toyama Prefectural University. He is now the director of Biotechnology Research Center at the same university. He’s research interests lie in efficient biocatalysis with several oxidoreductases for synthesizing chiral compounds and functional food materials, and biohalogenation.

5

Development of novel biocatalysts for producing chiral compounds

Nobuya Itoh

Department of Biotechnology, Faculty of Engineering, Biotechnology Research Center, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama 939-0398, Japan

E-mail: nbito@pu-toyama. ac.jp Abstract

The asymmetric reduction of ketones is a suitable method to obtain optically pure alcohols for pharmaceuticals and agrochemicals. BINAP-Ru and its derivatives are well-known organometallic catalysts for this purpose, and excellent performances have been demonstrated. However, several advantages of bio-based methods using enzymes or whole-cells systems over the BINAP process have been recognized in industry from the viewpoint of the cost of catalyst preparation, handling, and green chemistry. I describe an efficient method for the production of optically pure alcohols by the asymmetric hydrogen-transfer bioreduction of ketones in 2-propanol (IPA) and water medium using phenylacetaldehyde reducatse (PAR) from Rhodococcus sp. ST-10 and alcohol dehydrogenase from Leifsonia sp. S749 (LSADH) 1). These two enzymes were able to not only reduce the targeted ketones, but also served to reproduce NADH from NAD+ using IPA (Fig. 1).

To improve the conversion efficiency in high concentration of substrate and IPA, PAR mutant enzymes were engineered. PAR variant, Sar268/ HAR1 (A3S, I4L, E12G, D42L, K67R, L125M, S173P, A327V), was able to operate in relatively high concentration of IPA (> 20 % (v/v)) to achieve efficient conversion of concentrated substrate without altering the stereoselectivities.

In addition, it was confirmed that immobilization of the E. coli biocatalyst using glutaraldehyde (GA) and polyethyleneimine (PEI) increased the stability of this biocatalyst during operation. Immobilized/intact E coli biocatalyst (LSADH) could be applied for (R)-quinuclidinol synthesis as an NADH regenerator coupling with quinuclidinone reducatse (QNR) from Microbacterium luteolum (Fig. 2), and for chiral epoxides synthesis coupling with styrene monooxygenase (SMO) from Rhodococcus sp. ST-10 (Fig. 3).

Fig. 1. Asymmetric

hydrogen-transfer bioreduction of

ketones.

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References 1) N. Itoh et al., 2012. Appl. Microbiol. Biotechnol., 93:1075–1085. 2) K. Isotani, J. Kurokawa, N. Itoh, 2012, Int. J. Mol. Sci. 13:13542-13553. 3) H. Toda, R. Imae, N. Itoh, Tetrahedron:Asymmetry, 2012, DOI:10.1016/

j.tetasy.2012.09.017.

Fig. 2. (R)-(−)-3-Quinuclidinol production system

Fig. 3. Production of chiral (S)-epoxides using SMO and LSADH system.

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Tomohiro Mizobata Tomohiro Mizobata was born in Osaka, Japan, in 1967. He studied biochemistry with a focus on oligomeric protein folding under Professor Masanobu Tokushige at Kyoto University, Faculty of Science, and completed the Bachelor's and Master's program of the Division of Chemistry. After completing two years of study in the doctorate program of the same institution, he accepted the position of Assistant Professor, Faculty of Engineering, Tottori University in 1994. He completed his doctoral dissertation, entitled “Studies on the folding reactions of oligomeric proteins -Roles of the chaperonin GroE in the folding reaction-“, and obtained his Ph. D. in Chemistry from the Graduate School of Science, Kyoto University, in 1995. In April of 2003, he accepted the position of Associate Professor, Faculty of Engineering, Tottori University. The position has since transitioned to an associate professorship at the graduate school of the same faculty, as well as an equivalent position in the Institute of Regenerative Medicine and Biofunction, Graduate School of Medical Science, Tottori University. Tomohiro's research interests lie in elucidating the mechanism of protein folding, the specific means by which polypeptide chains assume their active conformations in vivo and in vitro. His research has led him to the study of the chaperonins, an ubiquitous group of proteins that facilitate the folding of proteins in the cell by suppressing polypeptide aggregation. Presently, he is involved in understanding in as much detail as possible the specific roles of numerous conformational changes that the E. coli GroEL chaperonin subunit undergoes as it acts to suppress the association and irreversible aggregation of various folding polypeptides, using a combination of mutational analysis and stopped-flow fluorescence analysis. Tomohiro Mizobata is the co-author of 44 research papers, 3 review articles written in Japanese, and one book chapter. He has also contributed to the Japanese translation of a biochemical textbook written in English.

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Elucidating the molecular mechanism of chaperonin-facilitated protein folding

Tomohiro Mizobata

Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori

University, 4-101 Koyama-cho Minami, Tottori-city, Tottori, Japan

After completion of the polypeptide chain by the ribosome, proteins must form a specific steric structure in order to become biologically active. It has been shown experimentally that the steric structure of proteins is dictated by the sequence of amino acid residues in the finished polypeptide chain (Anfinsen, C. B., Science 181, 223 (1973)). However, the underlying principles that govern the transition from linear chain to active protein conformation are not understood ("the protein folding problem"). This problem is compounded further by the fact that proteins often fail to fold, instead aggregating into inactive, insoluble deposits in the cell host under various conditions. Deciphering how and why proteins fold or do not fold is important, not only because it involves a fundamental scientific principle of living systems, but also because understanding protein folding is necessary in our efforts to utilize various biological activities industrially and treat many molecular ailments medically. Cells maintain a group of proteins whose role is to assist protein folding and minimize aggregation of proteins. Members of a subgroup of these "molecular chaperones", the chaperonins, act specifically to minimize aggregation of folding proteins by sequestering individual protein molecules within a barrel-like structure, and re-release them after an interval timed by the hydrolysis of ATP. The molecular mechanism of the chaperonins is a multi-step sequential process involving numerous intermolecular interactions, ATP hydrolytic activity, and precise alterations of the chaperonin system architecture. In this talk I will share our efforts in elucidating the molecular mechanism of the bacterial chaperonin component GroEL from E. coli. We mainly use mutagenesis to alter the subunit structure and activity of GroEL and probe its characteristics through a combination of functional and stopped-flow physicochemical analyses. In particular, I will discuss some of our recent experiments using circular permutation to alter the subunit structure of GroEL, and the effects of such mutations on the functional mechanism and dynamic behavior of this protein.

 

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9

鳥取大学GSCセミナーの歴史    

○第1回（Seminar  on  Green  and  Sustainable  Chemistry  in  Tottori），日本化学会・グ

リーンケミストリー研究会（17th  Green  Chemistry  Forum）と共催，平成20年12月10

日，とりぎん文化会館（鳥取県民文化会館）小ホール,  講師3名，出席者187名  

講師：上村明男（山口大学大学院医学系研究科  教授），「プラスチックの化学リサイクルに向

けた新しい方法」  

講師：丹羽   幹（鳥取大学大学院工学研究科  教授），「Y ゼオライトのブレーンステッド酸性

質発現と触媒活性」  

講師：萩原久大（新潟大学大学院自然科学研究科  教授）「イオン液体固定化触媒（SILC）とグ

リーンケミストリー」  

講師：  Professor  TECK  PENG  LOH（Nanyang  Technological  University,（Singapore））

“Ionic  Liquids  as  Green  Solvents  &  Catalysts  for  Organic  Synthesis”  

 

○第2回（Seminar  on  Green  and  Sustainable  Chemistry  in  Tottori  2009  (1)）（科研

費，特定領域研究「イオン液体の科学」，触媒学会，石油学会と共催），Ｈ21年11月14日，

工学研究科大講義室，講師13名，出席者167名  

講師：Professor  Douglas  MacFarlane(  Monash  Univ.,  Australia)”  Ionic  Liquids  and  

Global  Sustainability”  

講師：Dr.  Asako  Narita  (Kyoto  University,  Japan)  “Ionic  Liquid-modified  Inorganic  

Nanoparticles  and  their  Biomedical  Applications”  

講師：Dr.  Hideo  Midorikawa  (Asahi  Kasei  Chemicals  Corp.,  Japan),  “Environmental  

Friendly   Process   for   Producing   Cyclohexanol   from   Benzene   by   Using  

Heterogeneous  Catalysts”  

講師：Dr.   Kazu   Okumura   (Tottori   Univ.,   Japan),   “In   situ   X-ray   Absorption  

Spectroscopic  Study  of  Highly  Dispersed  Pd  Species  Active  in  the  Suzuki-Miyaura  

Reactions”  

講師：Professor  Toshiyuki  Itoh  (Tottori  Univ.,  Japan),  “Iron  Salt-catalyzed  One-Pot  

Nazarov  Cyclization  /  Michael  Reaction  of  Pyrrole  Derivatives  

講師：Professor  Bohari  M.  Yamin   (Univ.  Kebangsaan,  Malaysia),  “Structural   and  

Complexation  Studies  of  Fluorophenylthioureas”  

講師：Dr.  Hyunjoo  Lee  (KIST,  Korea),”  Alkyl  Polyfluoroalkyl  Imidazolium  Ionic  liquids:  

Synthesis  and  Characterization”  

講師：Dr.   Hisashi   Shimakoshi   (Kyushu   Univ.,   Japan),   “Bio-related   Tetrapyrrole  

Catalyst  with  Ionic  Liquid”  

講 師 ： Professor   Kenji   Takahashi,   (Kanazawa   Univ.,   Japan),”   ormation   of  

Anhydrosugars  from  Cellobiose  in  Ionic  Liquids”  

講師：Dr.  Mayumi  Nishida  (Koei  Chemical  Co.  Ltd.,  Japan),  ”  The  Development  of  

Koei’s  Ionic  Liquids”  

講師：Professor   Seiji   Suga,   (Okayama   Univ.,   Japan),   ”   Electroorganic   Synthesis  

Using  Micro  Reaction  Systems”  

講師：Professor  Toshio  Fuchigami  (Tokyo  Institute  of  Technology,  Japan),”  Highly  

Selective  Fluorination  of  Organic  Molecules  and  Macromolecules  in  Ionic  Liquids”  

講 師 ： Professor   Junko   N.   Kondo   (Tokyo   Institute   of   Technology,   Japan),  

“Crystalline  Mesoporous  Ta2O5  Photocatalyst  for  Overall  Water  Splitting”  

 

○第3回（Seminar  on  Green  and  Sustainable  Chemistry  in  Tottori  2009  (2)）Ｈ21

10

年12月1日，工学研究科代講義室,  講師2名，出席者154名  

講師：Professor  Pedro  Lozano  (University  of  Murcia,  Spain),  “Enzymatic  Catalysis  in  

Ionic  Liquids  and  sc-CO2  Biphasic  Systems”  

講師：Professor  Joe  Chappell University  of  Kentucky,  USA),“Evolving  the  Catalytic    (

Specificity  of  Terpene  Biosynthetic  Enzymes  and  the  Development  of  Sustainable,  

Robust  Production  Platforms  in  Yeast  and  Plants”  

 

○第4回（2010年度GSC  in  Tottori（1））（日本化学会，第53回中国四国産学連携化学

フォーラムと共同開催）Ｈ22年9月20日，工学研究科大講義室，講師5名，出席者177    

特別講演：  J-E.  Bäckvall（ストックホルム大学教授）” A  Biomimetic  Approach  to  Green  Organic  Transformations”  

特別講演：  B.  K.  Mihovilovic（ウイーン工業大学教授）“Bioorganic  Chemistry  in  

Sustainable  Synthesis”  

講師：國信洋一郎（岡山大学大学院自然科学研究科  助教）「不活性結合の切断を鍵とする新規

有機合成反応の開発」  

講師：米山公啓（広島大学大学院工学研究科  助教）「安全・安価な金属触媒を活用した有機合

成反応」  

講師：依馬  正（岡山大学大学院自然科学研究科  准教授）「多重水素結合部位を有するキラル

大環状化合物の不斉識別機能」  

 

○第5回（2010年度GSC  in  Tottori  (2)）(日本化学会，触媒学会，石油学会，化学工学会

と共催)，H22年11月13日工学研究科大講義室，講師4名，出席者188名  

講師：Suk  Bong  HONG  (Pohang  University  of  Science  and  Technology,  Korea)  

“Zeolite  Syntheses  via  a  CDM  Approach”  

講師：Shinji  INAGAKI  (Toyota  Central  R&D  Labs,  Inc.,  Japan)      

“Synthesis   of   Optically   Active   Periodic   Mesoporous   Organosilicas   toward   the  

Construction  of  Artificial  Photosynthesis”  

講師：  Akira  MIYAMOTO  (Tohoku  University,  Japan)  

“Multi-level   Computational   Chemistry   Methods   for   Green   and   Sustainable  

Chemistry”  

講師：  German  SASTRE  (Instituto  de  Tecnologia  Quimica  UPV-CSIC,  Spain)  

“Synthesis  of  Octahedral  Metal  Oxides  with  Pore  Structures”  

 

○第6回（2010年度GSC  in  Tottori(3)），（第1回イオン液体討論会（イオン液体研究会）

と共催）  

平成23年1月17日,18日，とりぎん文化会館，参加者186名  

特別講演：R.  Rogers（アラバマ大学  教授，米国）“Ionic  Liquid  Solvents  for  the  Grand  

Challenge  Inherent  in  a  Biorefinery:  Extraction  and  Separation  of  Lignin,  Cellulose,  

and  Hemicellulose” 特別講演：M-J.  KOO（インハ大学  教授，韓国，韓国生物工学会会長）“Application  of  

Ionic  Liquids  in  Bioconversion  Process”  

 

○第7回（2011  Green  Sustainable  Chemistry  Seminar  in  Tottori  (1)）  

2011年12月15日（木），共通教育棟A20講義室，出席者93名，講師3名  

講師：久枝良雄   （九州大学大学院工学研究院   教授）「Bio-inspired   Catalysts   for  

Degradation  of  Environmental  Pollutants:  Lessons  from  Metalloenzyme（バイオイン

スパイアード触媒の創製と環境浄化への応用）」  

講師：稲永純二  （九州大学先導物質化学研究所  教授）「Green  Asymmetric  Catalysis  with  

11

Diionic   Chiral   Sc-Complex   in   Ionic   Liquid:   An   Organic   Solvent-Free   Catalytic  

Asymmetric  Reaction  Process（有機溶媒フリーの不斉反応プロセスの構築）」  

講師：Suojiang  Zhang  （中国科学院(北京)教授，プロセス工学研究所長）「Hydrogen  Bonds:  

A  New  Insight  Into  Ionic  Liquids」  

 

○第8回（2011  Green  Sustainable  Chemistry  Seminar  in  Tottori  (2)）  

2012年2月14日（火曜），工学研究科大講義室，出席者193名，講師3名  

講師：小川   順（京都大学大学院農学研究科   教授）「Valuable   microbial   functions  

pioneering   bio-based   industry-   development   of   bio-lipid   platform   and  

biotransformation  」  

講師：酒井貴志（岡山大学大学院自然科学研究科  教授）「New  and  Efficient  Catalysts  for  

Activation  of  Carbon  Dioxide  and  Epoxide  to  Produce  Cyclic  Carbonate」  

講師：Xin-Hui  Xing（中国，清華大学  教授）「Microbial  Evolution  Engineering  for  Microbial  

Strain  Improvement」  

 

○第9回（2012  Green  Sustainable  Chemistry  Seminar  in  Tottori  (1)）  

GSC研究センター設置記念講演会  

2012年10月14日（火曜），共通教育棟A20講義室，出席者152名，講師3名  

講師：奥村   和（鳥取大学大学院工学研究科  准教授）  

「Structure  and  catalysis  of  layered  NbW  oxide  catalysts  constructed  by  the  

self-assembly  of  nanofibers」  

講師：Dae  Yoon  Chi（韓国  Sogang大学  教授）  

「New   Concept   Nucleophilic   Fluorination   Assisted   by   1H-1,2,3-Triazol-3-ium  

Triflates」  

講師：吉田  潤一（京都大学大学院工学研究科  教授）  

「空間で時間を制御する合成化学」  

 

 

延べ参加者1497名，講師38名