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Bioengine

Enzyme engineering allows the optimization of virtually any enzyme into a powerful catalyst, which can be conveniently applied under industrial conditions. Commonly, directed evolution (Nobel Prize in Chemistry, 2018) is used to improve enzymes in iterative cycles of random mutagenesis and selection for user-defined improved attributes.

However, traditional mutagenesis approaches either necessitate the screening of vast enzyme variant libraries or come at the cost of superficial sequence space coverage.

BioEngine® can speed up the process of bringing your idea to the market.

Spurred by these limitations, Enzymaster has developed the BioEngine®, a proprietary directed evolution platform with integrated computational enzyme engineering. The implementation of computational hot spot identification, in silico enzyme library screening, and in silico recombination into the directed evolution cycle allows us to shift most of the screening efforts from the laboratory into the computer and cover a large sequence space of the enzyme, all while accounting for the real chemical process conditions.

Based on the computational results, we construct smart and small libraries of enzyme variants, which can be conveniently screened via HPLC or GC to characterize a comprehensive range of desired properties for these variants. This enables us to reach the desired biocatalytic process target in typically only 3-6 rounds of combined in silico and experimental directed evolution. Therefore, BioEngine® can significantly speed up the process of bringing your idea to the market.

Enzymaster has developed a proprietary in-house computational toolbox for structure guided combinatorial library design and enhanced diversity generation.

The BioNavigator® is a set of state‑of‑the‑art methods for computational enzyme identification, in silico activity and selectivity prediction and stability calculation under process conditions. This includes bioinformatics driven hot spot identification, focused combinatorial library design and in silico loop design.

BioNavigator® is a set of methods for computational enzyme identification.

AI and structure‑based recombination algorithms are applied for in silico pre-screening to enhance the combinatorial sequence diversity coverage beyond traditional random and site-saturation mutagenesis approaches, thereby increasing the sequence space coverage and identifying all important  sequence areas.

This approach allows the design of focused libraries (typically 1000–2000 variants/round) which reduce the number of required experiments and enrich the libraries with active hits, ensuring a maximum screening efficiency utilizing our BioEngine® technology. After each round of evolution, all confirmed hits are sequenced for knowledge generation and computationally analyzed by docking and (QM/MM)-MD Simulations on our in-house Linux cluster, as well as on the π-2-supercomputer at Shanghai Jiao Tong University or cloud based HPC, to analyze and improve our prediction and prescreening methods using our BioNavigator® technology.

our Technology for your products​

this is our
BioNavigator

computer aided Evolution

Traditional random and site-saturation mutagenesis methods mostly cover only a small range of the possible combinatorial sequence space, often leading to a local, rather than the global maximum. With computer aided evolution, in silico pre-screening combined with careful computational analysis of all reaction and evolution data of each screening and evolution round improves the in silico model after each round. This builds up additional knowledge-based and artificial intelligence driven models, which speed up the evolution progress by optimized library design, thus reducing the required amount of directed evolution rounds and increasing the overall sequence space coverage.

our Technology for your products​

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Facilities

The headquarters of Enzymaster is located in Ningbo (China). Here, our R&D team is based, backed by the supporting functions of our company such as marketing, general administration, and business development for the Asian markets.

Our BD office in Düsseldorf (Germany) is suitably located in the heart of Europe to connect with partners in all time zones and thus represents Enzymaster in the international markets.

Since 2013, our R&D lab space for enzyme engineering and process development work has expanded greatly to about 3,000 sqm. Our work modules are equipped with state-of-the-art technology, ranging from liquid handling robots in our high-throughput experimentation module, HPLC- and GC-systems in our analytics center, to fermenters with volumes of up to 15 L in our microbiology department.

Our process development center has the capability of up scaling biocatalytic transformations up to a 10 L scale including standard downstream processing techniques, such as extraction and distillation.

Located outside of Ningbo, our fermentation pilot plant allows us to conduct enzyme manufacturing at a 1,000 L scale using state-of-the-art downstream processing methods, such as homogenization, ultrafiltration, heat treatment, and spray and freeze drying.

For our bioinformatics, we have an exclusive account for the SJTU (Shanghai Jiaotong University) π-Supercomputer for computational enzyme engineering, with 500,000 CPU hours/year. Furthermore, our in-house computer resources allow for parallel Docking and MD simulations.

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