Enzyme Catalytic Platform

As a CRO advocating for green drug research and development, Medicilon has consistently aimed to advance the environmental sustainability of pharmaceutical processes through technological innovation. Medicilon has already utilized enzymes in process research and development. Relying on its strong chemical and biological background, Medicilon has established the Enzyme Catalysis Technology Platform to screen catalytic enzymes for specific reaction types and establish corresponding enzyme libraries to support process development and production.

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Enzyme Engineering Introduction

Enzymes, the cornerstone of synthetic biology, can catalyze diverse reactions, and could be used in various industry, such as food, pharmaceutical, chemical industry, etc.Enzyme engineering is the process of modifying the structure and function of proteins or creating new proteins based on the relationship between molecule structures and biological functions in order to finish the set target.

Medicilon Enzyme Catalytic Platform

01. Chemical Technology Platform
Development of Pharmaceutical Intermediates and APlsFunctional Chemical Development
02. Biotechnology Platform
Enzyme Development and ApplicationsEnzyme Production
03. Quality Technology Platform
Quality and Control ResearchInspection and Testing Services
Medicilon's Enzyme Catalysis Technology Platform integrates a chemical technology platform, biotechnology platform, and quality technology platform. The platform emphasizes combining chemical synthesis with biological enzyme catalytic synthesis, conducting research on the development and application of biological enzymes, and engaging in R&D and production of pharmaceutical intermediates and APIs using green biotechnology. Additionally, it provides high-end CRO and CDMO services, along with testing and quality research services to pharmaceutical companies.
Enzyme Catalyzed Reactions
Redox reactionsHydrolytic reactionsC-Het Atom formationC-C bond formation……
Natural/Unnatural Amino Acids
Enzyme selection or discovery, such as:
Amino-acid aminotransferaseAmino acid hydroxylaseC-N lyase……
Capability & Capacity
~600 m² Biological Lab.Our team own rich experiences in enzyme engineering.We can quickly perform data mining and enzyme evolution according to customers’ needs based on our mature bioinformatics and molecular biological platform.We can provide a more environmentally friendly and economical process based on our complete biotransformation ability.
Enzymes libraries building2000 enzymes used for diverse catalytic reactions Directed evolution of enzymesGene mutations libraries building, using the strategy of combining rational and semi-rational design.High throughput screening: plate screening, microplate screening, FACS screening Synthesis of modified nucleosideLow value added nucleosides converted into high value added nucleosides through enzymatic catalysis Synthesis of unnatural amino acidEnzymatic catalysis Synthesis of pharmaceutical intermediatesReduce chemical reaction steps and costs through enzymatic catalysis, and which is applied to process scale up

Table 1 The period of enzyme evolution in Medicilon
Jobs	Month 0.5	Month 1	Month 1.5	Month 2	Month 3
Finish the experiment plan
Optimize the screening conditions (microplate & flask)
Construct and screen mutants
Combine positive mutants and screen

Application of enzymes and Enzyme engineering.webp

The period of enzyme evolution was ~3 months in Medicilon 1500~2000 mutants (including site directed mutants and libraries) were screened during this term.

Note: one library contained 90 mutants
Activity based classification for enzyme evolution and/or enzymatic processThe effect of early improvement exceeds the results of the later period

Development of Enzyme Process in Drug Synthesis

Mature platform abilityHigh speed collaborative cooperation of each functional modulesGood project management abilityTimely and effective information transmission

Medicilon Cases

Computer-assisted design were used for Penicillin G acylase modification, the substrate tunnels were rebuilt with combinatorial active-site saturation test.The activity enhanced ~5.8 fold, the conversion rate improve to 94.84% from 90.84% at the condition of 15 g/L PGM+15 g/L 7-ADCA.
The multi enzyme catalytic system of Vanillin synthesis was optimized through improving the activity of FCS and/or ECH.The yield of Vanillin enhanced obviously.
The immobilization ability of ACAE onto epoxy resin was improved by increasing the number of Lys on the surface of ACAE.The yield of 7-ACA improved.

Medicilon Enzyme Library

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Ketoreductase	Amino acid Dehydrogenase	Transaminase	Nitrile Hydratase	Phenylalanine Lyase	Hydroaminase
Alcohol Oxidase	Formate Dehydrogenase		Epoxide Hydrolase	Proline hydroxylase	Hydroxynitrile lyase
Monoamine Oxidase	Glucose Dehydrogenase		Amidohydrolase	Aldolase	Other Specialized Enzymes
Nitrile Reductase	Lactate Dehydrogenase		Ester Hydrolase	Decarboxylase
Nitroreductase				Nitrilase
Imine Reductase				Nucleoside Hydrolase
Ene Reductase

Currently, Medicilon has successfully established dozens of major biological enzyme libraries, including ketoreductase, ester hydrolase, imine reductase, nitroreductase, cyclooxygenase, and amide hydrolase. These libraries provide suitable biocatalytic solutions for various chemical transformations. These integrated enzymatic services reduce costs, shorten timeframes, and improve quality. With the implementation of numerous projects, Medicilon's enzyme library continues to be optimized and expanded. Additionally, Medicilon will conduct research on immobilized enzymes and coenzymes.

Medicilon’s R&D capabilities in the field of synthetic biology

With the continuous advancement of synthetic biology technology, an increasing number of enzymes with specific catalytic functions are being used as biocatalysts to achieve reactions that are challenging with chemical catalysts. These enzymes also serve as catalytic components to construct functional modules in synthetic biology. Medicilon has already established a strong presence in this field. Through the assembly of different enzyme components, Medicilon has achieved breakthroughs in designing synthetic routes for numerous target molecules. We offer a variety of services including:
Construction and optimization of cell factoriesEnzyme screening and optimizationEnzyme immobilizationMulti-enzyme cascade reaction construction and optimizationFermentation process control and optimizationProtein purification
In the future, Medicilon, as a one-stop biopharmaceutical preclinical R&D service platform, will continue to explore and apply more innovative green chemical technologies. Our aim is to achieve more environmentally friendly, safe, efficient, and economical process development and production, creating innovative products for clients around the globe.

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