Community Research and Development Information Service - CORDIS

H2020

APEX Report Summary

Project ID: 666346

Periodic Reporting for period 1 - APEX (Advanced Process Economics through Oxidoreductases)

Reporting period: 2015-04-01 to 2016-03-31

Summary of the context and overall objectives of the project

MetGen is a venture capital financed SME that has invented a disruptive, cost-efficient technology to develop industrial enzymes. The enzyme solution, MetZyme®, is based on thermostabile oxidoreductase enzymes with wide pH tolerance, designed to break recalcitrance of lignocellulosic biomass in harsh industrial conditions. Small scale pilot studies done together with large industrial customers have shown that these enzymes have the potential to significantly improve the economic and environmental sustainability of paper, chemicals, and biofuels.
The current Pulp & Paper (P&P) processes consume plenty of energy and chemicals, needed mainly for pulping and bleaching of the cellulosic biomass. MetZyme® can help an individual mill save as much as 1.5 million euros a year, based on the energy savings, reduced chemical usage and improved fibre quality. MetZyme® also allows optimizing the effectiveness of the catalysis of lignin and sugar conversion, enabling the production of low-cost cellulosic fibers and sugars. This supports the production of second-generation biofuels and bio-based chemicals and thus paves the way to sustainable European bioeconomy.

Within this APEX (Advanced Process Economics through Oxidoreductases) project, MetZyme® is going to be brought to industrial production for market demonstration at commercial scale within two target industries: P&P mills and biorefinery pilots. Both these industries are in a great need of more efficient processes with lower costs, and MetGen can offer them cost-efficient, tailored enzyme solutions. The current enzyme solutions do not function in the harsh industrial conditions (high temperature, pressure, high/low pH and short retention time) that MetGen’s enzymes are adapted for. The use of competing enzymatic solutions requires alterations to the process and capital investments, whereas MetZyme ® is used as a drop-in solution that requires no or very small capital investment. As processes, pre-treatment systems and conditions differ between customers, it is important to be able to adapt the enzymes to different needs. Due to the experience in genetic engineering and large base of available enzyme strains, MetGen can offer customized enzymes to each customer and for a variety of lignocellulosic substrates. In addition, biorefinery and P&P processes have significant similarities, allowing the enzymatic solutions developed for P&P to be directly used in many biorefinery applications.
In the APEX project, MetGen will illustrate the full potential of MetZyme®, the novel production system, and the team behind it by transferring the effects proven in lab and pilot scale to commercial applications. Furthermore, this will be done in an economically feasible way – changing the perception that enzymatic solutions are expensive in comparison to mechanical or chemical ones, and being a strong competitor for these on the target markets. MetGen aspires to be recognized as one of the world’s most significant enzyme developers and providers. The APEX project makes it possible for the company to bridge the gap between pilot and industrial scale, and thus become profitable by the end of this project.
The main objectives of the APEX project are to

1) scale up the production process of MetZyme® from the 400 l lab-scale pilot capacity up to 10 m3 and further, and to commission the large-scale industrial production in the scale of 50 m3–150 m3 at European contract manufacturers’ facilities;

2) reduce the production costs (50 % reduction of raw material costs, 100 % improvement in fermentation yield, 60 % improvement in productivity)

3) optimise logistics and the whole supply chain in order to further improve MetGen’s competitiveness;

4) demonstrate and quantify MetZyme®’s customer benefits in field trials to allow for market uptake
a. P&P: energy savings of up to 30 % and bleaching chemical reduction of up to 50 % in thermomechanical pulping,
b. biorefineries: 50-80 % reduction in the amount of cellulase needed, time for hydrolysis reduced from 72 to 24h;
c. The data from the trials, demonstrating the safety and potential of energy savings and quality improvements, will be essential for convincing potential customers also in new markets.

5) by the end of the project, serve 1–3 large European customers in the P&P industry with an enzyme solution produced by 2–3 European contract manufacturers, with enzyme concentrate volumes of 500m3/annum. This translates to an annual fermentation of more than 5,000 m3.

6) make MetGen ready for the biorefinery market replication by demonstrating the chemical and economic feasibility of MetZyme® in collaboration partners’ processes, proving its effect on the pilot scale and developing necessary cost models.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In section 1.1 of the DoA annex there is a list the specific objectives for the project. In the following the list is covered with remarks on current status on the objectives.
1) scale up the production process of MetZyme® from the 400 l lab-scale pilot capacity up to 10 m3 and further, and to commission the large-scale industrial production in the scale of 50 m3–150 m3 at European contract manufacturers’ facilities;
• MetGen has successfully scaled-up several enzymes to 400L and 2 have been successfully industrialized to 50m3 production during project APEX. 3 technology transfers have been made to further improve the productivity of the technology platform. Robustness of the created technology platform can be illustrated by the fact that MetGen has now scaled up enzymes with 100% success rate. MetGe has been always able to repeat the performance in various scales.

2) reduce the production costs (50 % reduction of raw material costs, 100 % improvement in fermentation yield, 60 % improvement in productivity)
• Through the R&D work on the enzyme itself, production development and the successful technology transfers to production scale MetGen has reduced the cost of final product 10-fold during the project APEX. At the same time the fermentation yield has gone up by 5-fold. It is safe to say the objective is well met.
3) optimise logistics and the whole supply chain in order to further improve MetGen’s competitiveness;
• MetGen has been successfully able to supply up to 5000L valumes of material to customer site reliably on time. MetGen has also managed to ship material to Asia, North and South America, and has created processes for sales and logistics to rely upon. Outsourcing logistic services to 4P logistics company Wiima Oy has greatly helped in optimizing the logistics. For the second year of APEX MetGen needs to build and optimize inventories and put the supply-chain to true test with actual trailing sales in large quantities.
4) demonstrate and quantify MetZyme®’s customer benefits in field trials to allow for market uptake
a. P&P: energy savings of up to 30 % and bleaching chemical reduction of up to 50 % in thermomechanical pulping,
• MetGen has been able to demonstrate 32% energy saving for TMP in lab scale in Grenoble University CTP department for TMP applications. In mill trials 12% energy saving has been demonstrated with a drop-in enzyme solution.
• In tissue and packaging applications >50% energy savings in refining have been demonstrated in mill scale.
• Bleaching has been demonstrated in mill scale but in the addressed applications this has proven to be less interesting to the customers in relation to fibre quality improvement and energy saving
• MetGen has showed additional fibre quality improvements and process control improvements especially on the tissue and packaging applications.
b. biorefineries: 50-80 % reduction in the amount of cellulase needed, time for hydrolysis reduced from 72 to 24h;
• MetGen has shown ability to reduce cellulase dosing by >50% with pretreated lignocellulosic substrates. The results vary according to the material and pretreatment applied. Furthermore MetGen focuses to improve the hydrolysis performance of enzymes especially in biomasses with high dry matter content, as this enables significant Capex and Opex savings for 2nd generation biorefineries.
• MetGen has been able to reduce the time required for the hydrolysis from 72 to 48 hours with certain substrates without compromising the sugar yield or adding on cellulase dosage.
• It is worth noting that above mentioned benefits haven’t been achieved simultaneously. Improvements can be fully utilized either as reduced dosage or time, not both at the same time.
c. The data from the trials, demonstrating the safety and potential of energy savings and quality improvements, will be essential for convincing potential customers also in new markets.
• MetGen has used the data from successful mill trials to create business cases that support sales. MetGen now has 3 such business cases in active use: TMP energy saving, tissue application and fluting application for board.
5) by the end of the project, serve 1–3 large European customers in the P&P industry with an enzyme solution produced by 2–3 European contract manufacturers, with enzyme concentrate volumes of 500m3/annum. This translates to an annual fermentation of more than 5,000 m3.
• MetGen has lined up two immediate customers for tissue and packaging applications that match the criteria of being large European P&P companies. Final tests are being done in mill scale and enzyme used in these trials is paid by the customers.
6) make MetGen ready for the biorefinery market replication by demonstrating the chemical and economic feasibility of MetZyme® in collaboration partners’ processes, proving its effect on the pilot scale and developing necessary cost models.
• MetGen’s technology platform serves biorefinery industries as well as P&P industry. On top of current capability of creating novel enzymes in industry-leading time-frame (<1 year from idea to industrial solution), MetGen is also capable of utilizing enzymes created for P&P industry for lignocellulosic biomass processing.
• MetGen has created strong competence in application testing of woody substrates which aligns MetGen’s efforts in both industries: P&P and biorefining for renewable chemicals.
• MetGen has several large collaboration partners that are in possession of significant existing infrastructure in 1st generation biochemicals/fuels as well as pilot facilities in 2nd generation renewable chemicals.
• MetGen has been able to position itself a a first choice for many companies in search for technology partner in biotechnology and enzyme manufacturing
• MetGen has widened the network in biobased industries during and because of APEX and success in executing the industrialization and demonstration of products in industrial scale.
• MetGen has been contacted by potential strategic partners for assessment of future opportunities in this area. Negotiations are ongoing.
As a result of a successful execution, at the end of the APEX project, MetGen will with its current portfolio operate above the break-even point and be competitive against competing solutions.
• MetGen has – at half-way point of the project – already demonstrated unparalleled performance in industrial applications. MetGen continues to

1.2 Explanation of the work carried per WP
1.2.1 Work Package 1
Explain the work carried out in WP1 during the reporting period giving details of te work carried out by each beneficiary involved.
· Yield improvement: Making the processes as efficient and productive as possible. This includes 1) robust production protocol in industrial scale with > 90 % success rate, 2) production cost reduction to reach a > 20 % production margin, and 3) productivity improvement [µkatal/€] by 60 % from 200 µkatal/€.
o MetGen has conducted 11 Fermentations in industrial scale with the contract manufacturers selected within this project. The success rate has been 10/11 (91%), where single fermentation has failed due to technical malfunction of the agitator.
o MetGen has easily reached > 20% production margin during the first year of APEX.
o MetGen has been able to improve productivity by more than 4-fold to > 800µkatal/€
· Scaling up the process to enable the production of enough enzymes for verifying the process in 50 m3 industrial measurements during two-week trials.
o MetGen has produced enough material for all the mill trials conducted or scheduled.
· Constant improvement of existing enzyme production processes. Creation of new processes for biofuel in 1 l  400 l  10 m3  150 m3.
o MetGen has improved enzymatic solutions in biorefinery applications according to the results in application testing. The new specifications of the products have been taken in account in production and supply-chain to provide for optimal solution technically as well as economically.
o MetGen has standardized processes in order to have an cumulative positive impact on every enzyme developed, scaled up, and commercialized.
o MetGen has created a complete technology – ENZINE® – platform (Figure XXX) to serve our customer industries, including renewable chemicals.

1.2.2 Work package 2
· Initial validation testing for feasibility and safety of the application at customer sites (1-2 days industrial scale testing for each customer)
· Two week trials in five paper mills for the P&P production; together with potential customers
· Accurate, quantitative information on the cost and energy savings as well as the enzymatic process compared to conventional processing

1.2.3 Work package 3
· Provide accurate, quantitative information on 1) improved fermentable sugar yield, 2) reduction in technology costs, mostly created by enzyme costs and 3) process improvements enabled by the enzymatic process, compared to conventional processing
· Professionally conducted trials that fulfil partners’ expectations on service, expertise, design of experiments, results, and reporting.

1.2.4 Work package 4

· Creation of technology transfer packages and process descriptions
· Creation of standard operating protocols (SOP)
· Technology transfer to relevant production scale at two contract manufacturing sites
· Successful technology transfer (+50 % specific enzyme yield in comparison to pilot scale)
Continuous improvement of production processes in collaboration with the selected contract manufacturers

1.2.5 Work package 5
In order to ensure the increased economic and environmental sustainability, profitability and competitiveness of the process, the solution and MetGen, it is crucial to assure good quality and market acceptability of the enzyme solution, as well as the speed of deliveries. Thus, logistics and the whole supply chain must be developed and the regulatory, safety and environmental regulations mapped and analysed. In addition, a LCA study is needed.
In order to achieve this, the objectives of this work package include
· Optimization of the supply chain, including inbound and outbound logistics.
o MetGen has, together with Wiima Logistics Oy, continuously developed the reliability of supply-chain.
o MetGen has optimized the production process and raw materials to be more affordable and easy to source for our contract manufacturers
o MetGen has created inventories of enzymes to supply industrial volumes with expected speed
· Optimization of economics; economies of scale in purchases of raw materials.
o MetGen utilizes the contract manufacturer’s size and 4P logistics to gain the economies of scale.
o MetGen has identified the largest cost impacts of raw materials and chemicals which can be sourced for less once the continuous production begins. Furthermore, MetGen has readily mapped out suppliers for the chemicals in question.
· Risk mitigation in the supply chain and inventories.
o MetGen’s enzymes are robust and formulated products very stable. This provides for good shelf-life in refrigerated conditions (>6 months). The liquid formulation was developed within this project.
o MetGen has been able to explore the potential risks related to supply thorugh trials in various scales, including but not limited to, sending material outside EU and handling the tolls and custom clearances.
o MetGen has refined the supply related processes according to the learnings and reserved sufficient inventories and time for reliable deliveries.
o MetGen foresees a significant efforts to be needed in this area for the next year of APEX, as the trailing sales begin and the supply-chain is fully put to use.
· Ensuring that the necessary regulations, registrations and labels are known and implemented to support the market uptake of MetZyme. Doing an LCA study.
o MetGen continues the REACH registration together with other enzyme manufacturers.
o MetGen provides the MSDS and general enzyme safety documents with each delivery of enzymes.
o MetGen fully complies with the laws and regulations in all geographical, economic, and industry areas.
o MetGen has not yet initiated the LCA study within this project.

1.2.6 Work package 6
· Achieve an efficient and quick transfer of the developed enzyme product from the lab scale into the industrial scale and markets.
o MetGen has developed a set of standardized protocols tied together to form an technology platform – ENZINE® (figure XXX).
o ENZINE® also outlines MetGen’s service concept from customer challenge to industrial solution with technical support.
· Make the product known to a large number of potential customers and collaboration.
o MetGen has become a well-known name within the biobased industries.
o MetGen has participated in various conferences and related events actively, often as a speaker, presenter, chair, or even sponsor. These events include:
• List of events attended

· Make the technology known to a wide audience, also including general public.
o MetGen has besides the physical attendance to the industry events also launched a new website as well as increased activity in social media, mainly through LinkedIn.
o MetGen has created a strategy to leverage on news and successes through distribution of information through social media. This work continues together with a coach sponsored by EC through SME-instrument.
· Ensure a successful market replication and commercialisation of the product.
o MetGen utilizes the previously mentioned sales concept and technology platform to support the sales and marketing.
o Sales process has been created anew during this project and the work on improving the processes continue.
o MetGen has hired new talents to the customer interface to support the technical service and value-addition to the customer industries with biotech expertize.
o MetGen has improved the capabilities and competences in application testing for better and more precise information on the enzyme impact on customer specific processes. This adds to the value provided to the customer. MetGen has learned that it provides as much expertise and service than it does enzyme solutions.

1.2.7 Work package 7
· Effective and efficient communication and reporting with the European Commission;
· Effective and efficient planning, organization and coordination of the project and its work packages;
· Ensuring the compliance of the project with the legal, contractual, reporting and financial requirements;
o MetGen is fully complying with legal, contractual, reporting, and financial requirements.
o MetGen has been very pleased with the hardworking and professional officers who have at times provided MetGen with advice and assistance.
o MetGen identifies a risk of insufficient resources also effecting the reporting: MetGen has a shortage of resources in relation to the work load. This is also reflected by the time limitations to write extensive reports.
o MetGen is very firm on requiring the work to be documented. However there is only one person reporting to European Commission and the detail of information is
Effective risk management, as well as the implementation of a contingency strategy, in order to minimize unforeseen deviations from plan significantly impacting the project’s budget or deliverables

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

MetGen has been able to industrialize it's enzyme production. At the same time MetGen has productized its technologies and service concept in to a technology platform called ENZINE®. This platform has demonstrated capabilities beyond state-of-the-art during this project. First and foremost the robustness of the technologies fused intot he platform ahave allowed for scale up of fermentation and down-stream processes with >90% success rate from lab (<2L) through pilot (400L) to industrial production (50m3). Furthermore, the technology platform allows the capability to create new and novel enzymes to address customer specific challenges in faster time than ever before. For a new pectinase with alkaliphilic characteristics the development from idea to industrial production took only 4 months. Even in harder cases MetGen aims to deliver an industrial solution within a year. It is noteworthy that previously it took up to 5 years to develop, screen, optimize a molecule and this is excluding the production development and scale up. Through creation of the platform these cross-disciplinary areas of expertize have been brought together in a way that far exceeds the efficiency of competing technologies.

Production technologies are extremely streamlined to allow for E.coli based production. There are other production strains that produce more g/kg protein than E. coli. The upside is that the creation and development of new molecules and novel characteristics is fast, allowing for tailor-made solutions for the customer. The production has been improved in many ways, including but not limited to molecule enhancement, fermentation optimization, and harvesting improvements; together bringing the production cost to competitive level with other industrial enzymes. The specific functionality in application enables MetZymes to work more efficiently than competing solutions. Therefore, MetZymes can be dosed in less quantity than others. The fast and adaptive production technologies are more sufficient way to address specific customer/industry challenges than high volume production of non-specific and generic enzyme. At its best -thanks to efforts in project APEX - MetZyme production is a zero-waste process. In most cases the only outlet of the process is ultrafiltration permeate that lets only some salts and such dissolved compounds to escape the process: these are relatively easy to handle in normal waste water treatment and do not pose any threat to environment. Furthermore, a waste-less production is affordable and efficient.

MetZymes are developed for lignocellulosic biomass, including wood for P&P industry. Whereas the market for energy saving in mechanical pulping has declined during the project, MetZymes have proven to work well in recycled fibre (RCF) applications including tissue and board manufacturing. These are very much growing markets. It is fair to say that MetZyme performance in these applications has exceeded the expectations of APEX and the new applications for the developed enzymes more than make up for the losses in energy saving application. It is good to mention that MetZyme saves a lot of energy (>50% in refining) in recycled fibre applications as well, it is just no longer the primary benefit: strength & quality improvements that lead to increased process control and production are more important to the customer. Furthermore, this application is more likely to create even more jobs in Europe and through material savings the impact on environment is at least as big as through energy savings in thermomechanical pulping.

MetGen has been gaining competence in pulp and paper testing as well as biomass evaluation and analysis. This know-how on the application side is extremely important part of the technology platform: application testing with relevant substrates and process conditions are the only way to guide R&D towards customer specific solutions. MetGen has developed application testing capabilities to be on par or beyond state-of-the-art in comparison to other enzyme manufacturers. Especially companies who are in business of blending generic enzymes (meant for other applications) into P&P enzymatic cocktails are always dependent on original manufacturers changes on product and can never meet the customer demand on molecular level. This sets MetGen far apart from most of the competition in P&P market. The bigger enzyme companies, such as Novozymes and DuPont do not consider forestry industry as a big enough market to address R&D efforts for bespoke solutions. MetGen has found a good niche for operations during project APEX.

Furthermore, the expertize gained on wood-based materials working with P&P customers is complementary to any form of lignocellulosic biomass fractionation and hydrolysis. All the solutions created can be utilized on both markets. The larger the MetGen library of prototypes and capabilities grow, the more solutions we can offer on biorefinery side as well. MetGen grows on P&P markets to eventually compete in the entire biorefining space.

Related information

Record Number: 190206 / Last updated on: 2016-11-09