Enzymer - Fra forskning til

kommerciel produktion hos

Novozymes
Visit from Biotech Academy Camp
16. October 2008
by
Hans Sejr Olsen
16/10/2008
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Program

 09:15 – 09:45 Introduktion (HSO) i 1JM.02

 09:45 – 10:00 Kaffepause
 10:00 – 11:00 Rundvisning i Pilot Plant (JDy)
 11:00 – 12:00 Undervisning fordelt mellem NZ
forskere i 1JM.02
 12:00 – 13:00 Frokost i 1JM.02
 13:00 – 16:00 Laboratorieøvelser i bygning
8G/8G1.18 under ledelse af NZ forskere
 16:00 – 16:15 Afslutning i 8G1.18
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Industrial Enzymes

Detergent

Starch

Fuel
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16/10/2008 NOVOZYMES PRESENTATION

We lead the way in finding sustainable

solutions for forward-thinking companies
- Environmental impact comparisons

MINUS
CO2 COST PRODUCING 1KG ENZYME:

PLUS : 1-10 KG
3,800 KG
3,400 KG
CO2 REDUCTION USING 1 KG ENZYME
IN DIFFERENT INDUSTRIES :
UP TO 1,300 KG CEREAL

MINUS : 600 KG BIOCATALYSIS

100 KG 150 KG 150 KG 200 KG

30 KG 40 KG
OIL & FATS

PAPER

FOOD
TEXTILES BIOETHANOL DETERGENT
ANIMAL FEED LEATHER
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Industries for enzyme uses

 Beverage  Forest Products  Oils & Fats

Alcohol

 Fuel Ethanol  Special Food

 Brewing

 Fruit &  Textile

 Cereal Food Vegetables
 Starch
 Detergent  Leather
Industry
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Technologies

 Screening of microorganisms
 Cloning and expression of enzyme gene
 Protein engineering
 Fermentation
 Protein purification
 Formulation of industrial enzyme products
 Up scaling to industrial production
 Enzyme application technologies
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Screening nature
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Large collection of biological samples and

pure non-pathogenic microbial cultures
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Technology and development

platform

Process
Creating biological Nature’s diversity
diversity
Molecular evolution

1. screening

2. screening

Creating expression
system
Fermentation
Upscaling process Purification
Formulation
Production
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Cloning and expression of enzyme gene

Production of enzyme sample for application test

Expression of
Aspergillus
many enzymes High oryzae
through put
Fungal mycelium screening

Yeast or
E.coli

Preparation
Expression
of cDNA vector
cDNA marker
Production of enzyme
promoter as mono-component
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Screening for enzyme activity can be done

in many ways
Growth conditions inducing
enzyme production

Growth on
selective media

Detection of
enzyme activity

High
through put
Agar plates 96 wells 384 1536
wells wells
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Man-made diversity

We develop and utilise state of the art technology to

create improved protein molecules from existing
proteins, with respect to the following characteristics:

Stability Temperature
Activity pH
Performance Chemicals
Compatibility Other proteins
Specificity Pressure
Expression Chelants
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Protein engineering
- directed evolution
Improved alkaline
Native enzyme
activity

Altered
specificity

Improved
thermostability

omutations
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Some of Novozymes’ protein engineered

products
Enzyme Mutation method Advantages
Termamyl LC Hybrid, Enhanced low calcium
(amylase) site specific activity

Termamyl SC site specific Enhanced low calcium;

(amylase) and specific activity

Liquozyme site specific Enhanced performance

(amylase) and thermostability

Duramyl (amylase) site specific Enhanced oxidation

stability

Lipoprime (lipase) Directed evolution Enhanced performance

Kannase (protease) Directed evolution Enhanced performance

Peroxidase variants Random; Enhanced stability with

site specific; H2O2 and thermostability

directed evolution
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Strong pipeline to support sales growth:

over 100 projects - approx. 13% of sales spent on R&D

Micro- Bio-
Enzymes polymers
organisms
for for
&
pharma
industrial industrial proteins
use
use

Over 85% of Approx. 5% of Up to 10% of

R&D resources R&D R&D
resources resources
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The patent portfolio*

Detergent
Grain Processing
Expression
Other Technical
Diversity generation Fermentation Animal Feed
Screening Recovery Cereal Foods
Formulation Other Food
Outside enzymes
Enzyme classes
Discovery Production
~5-10% ~15-20%

Current
* 791 patent families (ultimo 2003) & new bus.
(125 patent applications were filed in 2004) ~75%
Production
16/10/2008
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16/10/2008 NOVOZYMES PRESENTATION

How we produce enzymes

READY TO SELL
FERMENTATION
PRODUCTS

FORMULATION
RAW MATERIALS LIQUID PRODUCT

PURIFICATION

GRANULATED PRODUCT

MICRO-ORGANISMS
MICRO-ORGANISMS TO BE INACTIVATED

I/II
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16/10/2008 NOVOZYMES PRESENTATION

How we produce enzymes

FERMENTATION RECOVERY GRANULATION

 Fermentation of one of a  Filtration of the fermentation  Formulation and standardisation

number of specifically selected
production micro-organisms
(bacteria or fungi) under sterile
conditions
 Production of the desired
enzyme by consumption of
carbohydrates, proteins, salts,
water and energy
 Transfer of the fermented broth
to recovery
broth of the enzyme into solid
 Purification of the liquid phase granules to encapsulate the
containing the enzyme enzyme - and provide the right
 Concentration of the liquid property of the product
enzyme to desired enzymatic (solubility, colour, etc.)
activity
 Stabilisation and
standardisation of a liquid
product - or
 Standardisation of a liquid
concentrate for granulation
II/II
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16/10/2008 NOVOZYMES PRESENTATION

Undisputed world leader in industrial

enzymes

Total market value

2007: DKK 15 billion

Danisco
21%
Others
24%

DSM
5%

BASF
3% Novozymes
47%

Source: Novozymes’
estimate 2007
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16/10/2008 NOVOZYMES PRESENTATION

Global coverage with strong emerging

market presence

Sales Offices

Production

Research

Turnover by
region 2007
Latin Europe,
Asia Pacific America Middle
20% 7% East and
Africa
41%

North
America
32%
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16/10/2008 NOVOZYMES PRESENTATION

Employees

Sales,
Marketing and
Corporate staff
35%

 More than 5,000

employees
worldwide Research and
Production
50%
Developement
 Around 2,200 in 15%

Denmark
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16/10/2008 NOVOZYMES PRESENTATION

We want to be the world leader in cell culture

for the Biopharmaceutical industry
Turnover by
region 2006 Growth in 2007: 100 %

Expected Long term

growth 10 – 15 %

Source: Novozymes’
estimate 2007
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www.novozymes.com