ROUNDTABLE INTERVIEW: The Promise of Protease

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1 > Global News Categories: Corporate News ROUNDTABLE INTERVIEW: The Promise of Protease Source: Feedinfo News Service (dated 20/05/2014) 20 May Responding to significant market interest and demand, DSM, in collaboration with its feed enzymes partner Novozymes, recently hosted the 'Feed proteases science into practice' seminar in Noordwijk, the Netherlands. It was an occasion for the established scientific community to provide an overview of the latest practical and technical insights on the use of proteases to optimize nutritional performance. The recent seminar follows on from the first ever Global Feed Protease Dialogue held in Copenhagen in June The Noordwijk event was specifically developed to disseminate the key findings of the Copenhagen meeting to a wider audience of industry stakeholders, including nutritionists, feed manufacturers and meat producers. Inge Knap, Global Category Manager for Feed Enzymes at DSM commented: We now have a much deeper understanding of proteases functionalities and benefits than in the past. The key to delivering their full value in the field, however, is open discussion and collaboration between science and industry to share this knowledge. Our aim with this seminar is to bring leading experts together with industry representatives to facilitate two-way dialogue on the effective use of proteases in practice. Adam Smith Market Development Manager Proteases EMEA DSM On the sidelines of the Noordwijk seminar, Feedinfo News Service organized a meeting with several of the participants to discuss the protease potential. Joining in on the discussion were Adam Smith (Market Development Manager Proteases EMEA at DSM), Neil Duijster (Regional Category Manager Enzymes at DSM), Roselina Angel (Associate Professor at the University of Maryland), Aaron Cowieson (Principal Scientist at DSM), and Rick Kleyn (a consultant for Spesfeed in South Africa). [Feedinfo News Service] Dr. Smith and Mr. Duijster, why did you organize the protease seminars and workshops in , and not when RONOZYME ProAct was launched in 2008? Is the market more mature and understanding than it was six years ago? And has the application know-how of protease improved since the launch of RONOZYME ProAct in 2008? [Adam Smith] We like to do our home-work first. With

2 RONOZYME ProAct we brought a fundamentally new innovation to the market, in that sense you can really view this as pioneering work at the time the product was introduced. In the years that followed we actively worked with customers and the scientific community building up our understanding and field experience. We now have a much deeper understanding of proteases and judge the time is right to take up the dialogue with an audience as broad as possible and share our collective knowledge on the topic. [Neil Duijster] Indeed, five years of research and field experience has brought a lot of understanding. We can confidently say our know-how has increased drastically particularly in the area of application. Based on our current understanding of how RONOZYME ProAct interacts with different ingredients and dietary parametres we can now tailor our advise to a customer specific diet, ensuring we capture consistently the benefits of the product. [Feedinfo News Service] Given the huge potential of proteases today, why aren't they commonly-used in livestock and poultry diets as we speak? How do you explain this delay between scientific breakthroughs and market penetration? [Adam Smith] Like all new innovations, it takes time before the market accepts the benefits claimed by the producer no matter how good they may be. If you look back at phytase as an example of an enzyme almost universally used today this picture was very different in the first few years post launch. We also tend to forget that proteases have only been on the market for 5 years (3 in the EU). The fact that circa 30% of the global broiler industry has taken the decision to use a protease in this time perhaps should not be seen as a delay. [Feedinfo News Service] DSM says it is witnessing customers accepting protease much faster than they did phytase or carbohydrase when those products were first launched. Can you provide us with some data or examples to back up this statement? [Adam Smith] Take for instance the use of phytase in animal nutrition, although the technology was introduced in the early 1990 s it was not until the ban on the use of meat and bone meal in the year 2000 that in Europe the adoption of phytase really accelerated. Even then some customers only started exploring the full benefits of phytase during the 2008 spike in phosphate prices. These things take time, and indeed, in that respect the rate of adoption of protease is moving fast. Aaron Cowieson Principal Scientist at DSM [Feedinfo News Service] Dr. Cowieson, according to you, what concrete developments in protease feeding/technology occurred between the First Protease Dialogue in June 2013 (which you attended) and this May 2014 seminar? [Aaron Cowieson] It is important to note that the enzyme per se (RONOZYME ProAct) is unchanged during this time period so our focus has been on gaining deeper and more holistic understanding of mode of action and application optimization. Central to this effort has been two metaanalyses of all available data on the effect of RONOZYME

3 ProAct on ileal amino acid digestibility and performance. The digestibility meta-analysis contains over 800 data points and has shown clear relationships between the inherent digestibility of amino acids in the incoming raw material and protease response. In addition to confirming the validity of our current recommendations on protease response the metaanalysis also identified patterns in the amino acid effects of protease that are indicative of beneficial changes in endogenous amino acid flow. The performance meta-analysis contains almost 700 data points and has allowed us to identify key diet-level factors that promote performance effects of protease well beyond amino acid digestibility effects. Several joint projects have also started to further explore and validate the outcomes from both meta-analyses with particular emphasis on gut health and integrity and the interaction between protease and raw material quality. [Feedinfo News Service] Mr. Kleyn, as a practicing poultry nutritionist, what are the benefits obtained from the use of a protease today? What further information do you need to capture even more benefits for your clients? [Rick Kleyn] For me a protease brings three principal benefits to a commercial operation. Firstly, their use when following the suppliers recommendations leads to direct cost savings for each ton of feed. Secondly, proteases are a means of reducing the negative impact of using poorly processed soya products on poultry production. Lastly, but not least, a protease can bring about improved conditions in poultry housing, and although difficult to measure in monetary terms, improved environmental conditions lead to better animal welfare and improved performance. In terms of additional information needed, three areas would be of interest to me. Firstly, should we not be looking at flexible inclusion levels in diets? Secondly how do we make best use of protease in diets that contain multiple enzymes? and lastly, how much energy does a protease release? Rick Kleyn Spesfeed [Feedinfo News Service] What more can proteases deliver to the animal nutrition industry over the next 5 years? [Aaron Cowieson] It is logical and often convenient to think of enzymes in nutrient silos e.g. phytase for phosphorus, xylanase for energy, protease for amino acids. However, just as we now understand that the effects of phytase extend well beyond phosphorus it is becoming clear that the effects of protease extend well beyond amino acids. One example of this is evident in the performance meta-analysis mentioned previously. In this we saw many examples of RONOZYME ProAct improving weight gain and FCR by 5-10% relative to the appropriate control diet, a magnitude that is not readily explained by amino acid nutrient release values in isolation. We have a number of very promising leads to explore these unexpectedly large performance effects and are developing tools based on our substantial datasets in order to deliver these advantages to our customers. I expect that we will view proteases very differently in 5 years and the progression will be similar to the development of our understanding of phytase

4 i.e. the extra-proteinaceous effects of protease will become more evident in the value proposition. [Roselina Angel] In the next five years I can see a better understanding of the impact of proteases on a greater number of ingredients. This should allow for better application and greater effects in diets worldwide. As more synthetic amino acids become commercially available and used in the poultry industry, the role of proteases also becomes more important. In large part because industry is looking at using more synthetic amino acids to lower protein content in diets and costs. Lower protein results in lower concentrations of non essential amino acids, and already problems with this applications are being seen. Some exogenous proteases have a large impact on increasing digestibility of non essential amino acids and thus their role will be more important. Finally, as greater amounts and type of by-products have to be used for animal production, digestibility of all nutrients will tend to be lower. This widens the role for exogenous enzymes including proteases. Dr. Roselina Angel University of Maryland [Feedinfo News Service] The main focus of protease use to date has been on broilers. Can we expect applications with other animal species soon? [Neil Duijster] Yes, expect to see applications in other species soon. We focussed on broilers to start with as a species which not only represents a huge market but also because their fast turnaround time allowed us to increase our practical understanding of proteases as quickly as possible. By focussing on one species we could learn more quickly and then with that knowledge translate experiences to others. This does not mean that we have been ignoring other species at a scientific level. In fact evidence so far from experimental studies suggests the benefit in laying hens, turkeys and piglets are of similar magnitude in terms of digestibility and animal performance. Practical experiences in areas where regulation has allowed the use has also been very positive and already we have significant use in, for example, laying hens. [Feedinfo News Service] DSM has encountered a lot of success with RONOZYME ProAct with BRF, and in Latin America in general. DSM's Dr. José Otávio Berti Sorbara even says Latin America probably has the highest ratio of enzyme sales to feed production of anywhere in the world. What other global markets are showing signs of promise? [Adam Smith] Success with RONOZYME ProAct is by no means restricted to Latin America. Although launched almost two years later in the EMEA region due to increased regulatory hurdles, growth has been very swift with more than 20% of the EMEA broiler market already embracing its use. Cost savings have of course been important to this success but the potential of a protease as a solution to help producers in EU member states more easily comply with consumer and legislative challenges have also been important to sales growth in this region. In fact the strong economic, legislative and animal welfare pressure on broiler producers creates the perfect environment for protease which has benefits in all of these areas. Due to this situation we expect this market to continue to grow quickly. [Feedinfo News Service] Why is it important for DSM to involve leading academic researchers to raise the awareness of protease? Besides the additional outsider expertise, would you agree that the collaborations give you extra credibility?

5 Neil Duijster Regional Category Manager Enzymes DSM [Neil Duijster] Confirmation of DSM s findings and products by key academics is of course very valuable for the credibility of our marketing. However, our main reason for involving such experts in our activities is wider. Proteases are the most recent and innovative addition to the range of enzymes available for the animal feed industry, and although DSM is a leader in this field, but we can t do everything ourselves. Unlocking their biological potential to deliver maximum value for the industry demands the involvement of the leading minds in animal nutrition and physiology. DSM is uniquely placed with strong contacts in both academia and industry and can therefore bring together experts from both fields for open discussion on important topics. By sharing of knowledge and ideas in this way we can accelerate development of proteases way beyond that which could be done working purely in-house and this is of benefit not only to DSM but the industry as a whole. [Feedinfo News Service] What are the areas of research needed to more fully exploit the benefit of proteases? [Aaron Cowieson] I think we need a greater depth of understanding of the process of protein digestion at a fundamental level and in particular the role of endogenous protein flow and its incomplete recovery by the terminal ileum. Intestinal secretion/absorption is plastic and responds dynamically to the incoming nutrient mix. I am interested in the interactions between exogenous protease and endogenous protein flow and the contribution to true amino acid digestibility. I also think we need to do a lot more work to understand the co-operativity of phytase and protease as there are many potential areas here to explore including improved access to phytate, overlap in endogenous protein flow, protein efficiency, myo-inositol etc. [Roselina Angel] We need a better understanding of how feed proteins (by ingredient) are being digested along the tract and what are the real sources of measured undigested amino acids at the ileal levels in poultry. This should allow us to better understand what the rate limiting steps in feed as well as exogenous protein digestion are and this will in turn help get more from existing proteases and with developing new proteases. Additionally, we will be using more enzymes in combinations and this tends to change the ingredient and nutrient content of the diet. How these enzymes interact and what are the resulting digestible nutrient releases when they are used together has to be understood. [Rick Kleyn] Understanding better the mechanisms responsible for the effect RONOZYME ProAct has on gut health and integrity and in turn litter quality can only help with our understanding, but of equal importance as a commercial nutritionist is to understand the relationship between proteases and other enzymes already in feed. Are they additive, semi additive or non-additive? [Feedinfo News Service] Dr. Smith, what is your message to the customer who is receptive to the benefits of protease, but prefers to wait until the science has been fine-tuned before placing orders? [Adam Smith] Presentations in today s seminar have provided clear scientific evidence for the effect of a protease and showed that this can translate into practical benefits for the user, not least the EUR 2-6 cost saving on each ton of feed produced. Fine-tuning will of course add further to the value a protease can bring. However, such a process can as we see with other enzyme categories, take many years and whilst waiting for the last few % many of the core benefits are being missed out on. Our advice would therefore be to start learning about the benefit of a protease in your own organization using today s knowledge, start with conservative DIF/matrix values, consider diet responsiveness to a protease and start in your commercial operation where the benefits on gut health, litter quality etc. will be more pronounced. At the same time, follow carefully with your DSM partner fine-tuning activities and implement to get even more benefit as the science develops.