Scientific Developments in the Field of Enzymes

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1 Scientific Developments in the Field of Enzymes Dr.ir. Leon Marchal Director Nutrition & Innovation Frankfurt

2 Last lecture before lunch 2

3 Content Driver of past developments Current scientific status / Open questions Driver of new development Animal Type of enzymes poultry swine others phytase NSP + amylase + protease + others 3

4 What are the developments? (1/2) 4

5 What are the developments? (2/2) Look for reviews and meta analysis Understand what the drivers where of developments in the past which helps you to understand current and future developments 5

6 Phytase all hits

7 Who are the main patent applicants? Company Number of patents Novo Nordisk / Enzymes 73 Dsm (incl Gist Brocades) 23 BASF (incl. Verenium) 39 Dupont (incl Genencor, Danisco) 34 Vland 11 Ab enzymes /Vista 7 Challenge Group 4 Sunhy 4 Adisseo 4 Huvepharma 1 Indicative: Non complete list Patent licences #of patents impact Main players Consolidation New players (China) 7

8 Content Driver of past developments Current scientific status / Open questions Driver of new development Animal Type of enzymes poultry swine others phytase NSP + amylase + protease + others 8

9 # publications per year Publications per year last 100 years on Phytase Phytase Steady increase since late 80 s Looks like the increase flattens off Reaching maturity phase? 9

10 What drove the phytase development? (1/2) Initiator: legislation on manure (started in the Netherlands, Germany) Nutrient surplus of the Netherlands N P Now less than 20% of peak 10

11 What drove the phytase development? (2/2) Cost reduction in diets Increased price alternative EU ban meat and bone meal 1994 Increased price of organic phosphate Better price/performance ANF reduction; Amino acids and energy increase in diets Increasing efficiency of enzymes (round 2000 and recent) Liquid dosing / increased heat stability 11

12 Phytase Some recent themes: Super dosing (an effect above 1000 FTU?) still in debate Ca/P ratio in diets (meta analysis, M. P. Le tourneau-montminy et al 2012) Fish applications (review: Kumar et al, 2011 and Lemos et al 2015) Beneficial for ruminants? 12

13 Ruminants, exogenous phytase E. Humer, Q. Zebeli, 2015 Conflicting results, however seems related to overall P level in the diet 13

14 P quota for ruminants in NL Aimed at capping the total amount of P produced Incentive of farmers to maximise kg milk / kg P Wil drive down the P level in the diets Is an opportunity to look at phytases and NSP enzymes for ruminants Is a pronounced form of the global drive for increased protein efficiency 14

15 Content Driver of past developments Current scientific status / Open questions Driver of new development Animal Type of enzymes poultry swine others phytase NSP + amylase + protease + others 15

16 Where do we stand: piglets?

17 A. Torres-Pitarch et al

18 Main conclusions Phytase most consistent improvements in piglet growth, P digestibility, and bone mineralization. Protease supplementation increased feed intake Nutrient digestibility was increased mainly when multi-enzyme complexes containing protease and/or mannanase were included. Carbohydrases improved nutrient digestibility when supplemented as part of a complex; however, growth responses were not consistent. Need for experiments with protease and mannanase supplemented alone Interacting factors: particle size, nutrient density of the diet and feed form A. Torres-Pitarch et al

19 NSP enzymes Truly established: wheat based diets poultry Quite some evidence but also non response trials and variance: Swine in general Corn based diets Ruminants: not really successful until now (S. J. Meale, et al, J ANIM SCI 2014, 92: ) Exception amylase for high corn starch diets 19

20 Content Driver of past developments Current scientific status / Open questions Driver of new development Animal Type of enzymes poultry swine others phytase NSP + amylase + protease + others 20

21 Emerging field: promoting Gut health For example 21

22 Why is gut health becoming more important? AMR reduction But also emerging Reduction of high ZnO levels Cu reduced in piglets towards 25 ppm 22

23 Global Political Issue

24 Key issues Anti Microbial Resistance reduction 1) Limited human consumption of antibiotics 2) Right use of the different types of antibiotics 3) Limit use of antibiotics in livestock and pets

25 Background - Ban of the AMGP s in EC 1999 Tylosin, Spiramycin, Virginiamycin, Zinc-Bacitracin 2006 Avilamycin, Flavophospholipol, Salinomycin, Monensin NL: Total consumption increased

26 But with the right policies: 550 tons End of medicated feed 200 tons NL: Maran 2016

27 But also market driven PR and specific customer demand also drive AMR reduction

28 What are the effects of these developments? Gut health becomes very important Tendency to lower crude protein level in diets (decrease daily growth and reduction of fermentable protein levels) Request for solutions for specific pathogens pressure 28

29 Enzymes are one of the element in the toolbox 29 U. Gadde et al, 2017

30 How do enzymes change microbiota? (1) Reducing the undigested substrates (2) Generating short-chain oligosaccharides from cell-wall NSP with potential prebiotic effects Bedford (2000) Bedford and Cowieson (2012) Kiarie et al. (2013) 30

31 Feed enzymes Feed composition Individual microflora Feed processing 31 Kiarie et al. (2013)

32 Could we see new specific enzymes in the future? Aimed at specific pathogens or bacterial clases Some new, some old, but they could become relevant to market Both enzymes or antimicrobial peptides can produced by (the same) fermentation technology Lactoperoxidase? Lysozyme? Ovotransferrin? Etc For example 32

33 As an example of a approach Systematically unravelling all the components present in a natural situation like egg white Identifying the key elements to focus on 33

34 Main take home messages Monogastrics will see further drive for more value for money Ruminants a revisited because of changing situation for part of the market AMR reduction is the real key new driver Improving general gut heath it is important to understand the 4 key interactions We will see also the development of specific new enzymes/proteins against pathogens 34

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