Manufacturing technologies
Sustainable chemistry, Enzyme engineering, Artificial photosynthesis

Unified catalysis concepts from molecular design tosustainable chemicals and materials
Department of Applied Chemistry, Graduate School of Engineering
Professor Takashi Hayashi
https://researchmap.jp/20190602_Sun?lang=en

This research is conducted in the interdisciplinary field involving chemistry, biotechnology, and computational science and machine learning,with international joint research focusing on the development of substanceconversion, catalyst design, and chemical energy production technology. The collaboration between chemistry and biotechnology will lead tothe generation of novel catalysts and the development of processes that
contribute to sustainable material transformation. Our team’s researchinterests include the following topics; For example, the creation of new
biocatalysts by embedding artificial metal complexes in proteins, the catalyst design and enzyme modification using data science, the productionof chemical energy sources by artificial photosynthesis from ubiquitous
small molecules, the development of new catalysts using microorganisms
and chemical catalysts, and the preparation of biocompatible materials
using both microorganisms and chemical catalysts (Figure 1).

Catalysts are essential tools for material transformation in a sustainable
society. In particular, the conversion of inexpensive raw materials and sustainable resources into highly functional materials and chemical energy
sources (hydrogen, methanol, etc.), and the effective utilization of small
molecules obtained from the degradation of polymers are important current issues in synthetic chemistry and bioengineering. The development ofexcellent catalysts and processes that skillfully handle catalysts are crucialto solving these issues. This research started at the end of 2022 by thesupport of a Grant-in-Aid for Scientific Research on International Leading
Research from JSPS, and has already begun with collaborators from both
Osaka University and RWTH Aachen, Germany. One of our recent researchachievements is the construction of an artificial metalloenzyme consisting ofa protein called nitrobindin with a stable β-barrel structure where a rhodium
complex is inserted into the cavity via covalent bond with the side chain of
an amino acid residue as shown in Figure 2. The obtained artificial metalloenzyme is found to catalyze the synthesis of isoquinoline from acetophenone
oxime and alkyne. Furthermore, we constructed a chimeric protein by introducing the helix-loop-helix domain of another lipid-binding protein to the entrance of the nitrobindin cavity by genetic engineering. In collaboration witha group at RWTH Aachen, an expert in protein-directed evolutionary engineering, our group improved the domain and achieved a dramatic increasein the catalytic activity of isoquinoline synthesis. In addition, our group is
currently constructing various artificial enzymes by inserting non-natural
metal complexes into protein cavities and is challenging to obtain activities
that surpass natural enzyme reactions and to develop catalytic systems that
can handle reactions not found in nature (Figure 3).

▍ Significance of the research and Future perspective
The collaboration between the two fields, chemistry and biotechnology,
is expected to have an even greater impact on catalyst development,
which has so far been developed independently in the respective fields.
Through interdisciplinary international collaborations, this project aims tovigorously develop material transformations and materials using the latest
catalytic technologies as well as to integrate the academic concepts ofcatalysis (Figure 1). The final goal is to integrate chemical- and bio-catal-

Computational
Data Science
Organic/Inorganic
Chemistry

BioTechnology

UnifiedCatalysis
Concept

MaterialScience

CellularEngineering

ProcessEngineering

Figure 1 Various research fields related to catalysis and integration of
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Manufacturing technologies▍ Background & Results

ysis and unify the concepts of catalysis, focusing on developing and utilizing catalysts that contribute to bioeconomical material transformation.

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Figure 2 Development of new artificial metalloenzymes combining protein
and metal complex
CHCO2EtC(sp3)OHPh

Ph+ H2O2
C(sp3)+ EDA

M = FeM = Mn

OH
NN
M

NN

heme-bO

O

S

substitution
OOH

metalloporphycene“artificialcofactor”

H

M = FeOH
N

NONOFeNOH

O2

S+ H2O2

conversion of myoglobin
to artificial metalloenzyme

Figure 3 Construction of various catalytic reaction systems of myoglobinreconstituted with artificial metal cofactor

P a t e n t
Kato, Shunsuke; Schwaneberg, Ulrich; Hayashi, Takashi et al. Evolutionary engineering of a Cp*Rh(III) complex-linked artificial metalloenzyme with achimeric β-barrel protein scaffold. J. Am. Chem. Soc. 2023, 145, 8285-8290. doi: 10.1021/jacs.3c00581
Oohora, Koji; Onoda, Akira; Hayashi, Takashi. Hemoproteins reconstituted with artificial metal complexes as biohybrid catalysts. Acc. Chem. Res. 2019,
Tr e a t i s e52, 945-954. doi: 10.1021/acs.accounts.8b00676
Kato, Shunsuke; Honda, Kohsuke; Hayashi, Takashi et al. Chitin- and streptavidin-mediated affinity purification systems: A screening platform for enzyme
discovery. Angew. Chem. Int. Ed. 2023, 62, e20230376. doi: 10.1002/anie.202303764
URL http://www.applied-bioinorganic.jp/en/
K e y w o r d catalyst, enzyme, sustainable material conversion, energy conversion, bioeconomy