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Engineering Biology. © BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 Enabling a Knowledge-Based Bioeconomy CLIB International Conference 2013 Düsseldorf April 17 & 18, 2013 Jürgen Eck Vorstand / CTO

Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

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Page 1: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Enabling a Knowledge-Based Bioeconomy

CLIB International Conference 2013

Düsseldorf

April 17 & 18, 2013

Jürgen Eck Vorstand / CTO

Page 2: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

= Transformation of

Industries

Enabling BioEconomy

BioFuels / BioEnergy

Food/Feed/Agro

industry

Pharma

Medical Device

industry

Home and

personal-care

Pulp / Paper

industry Textile industry

Chemical

industry

En Route to the Knowledge Based BioEconomy (KBBE)

Page 3: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Inventor Entrepreneur Financier

• Schumpeter (1912)

-> +

Economic development involves transferring capital

from old businesses using established methods of

production to businesses using new, innovative

methods.

The Theory of Economic Development:

An Inquiry into Profits, Capital, Credit, Interest, and the Business Cycle

Joseph A. Schumpeter (1912)

Business Cycles: A Theoretical, Historical and Statistical Analysis of

the Capitalist Process

Joseph A. Schumpeter (1939)

En Route to the Knowledge Based BioEconomy (KBBE)

Page 4: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Sustainability

triangle Societal drivers Ecological drivers

Economical drivers

Underlying fundamental trends

Innovation need

Margin pressure / Production costs

Raw material and energy pricing

Globalization / Competitive Speed

Increasing demands in emerging markets

Underlying fundamental

trends

Regulation issues

Raw material access

Disposal of waste

Green chemistry

Underlying fundamental

trends

Growing population

Aging population

New markets

Demand for healthy products

Key drivers from industrial perspective Source: Brundtland report 1987, BRAIN

En Route to the Knowledge Based BioEconomy (KBBE)

Page 5: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Drivers of an industrial transformation process

Enabling New Products

Alternative Processes

• True & Desruptive Innovations

• Growth / Market entry with novel Products

• Enabling new Applications and Concepts in

different industries (chemistry, material, energy,

pharma, …)

• Cost reduction by improved production processes

• Increase in quality of the product

• Accessing new raw materials / renewable feedstock

En Route to the Knowledge Based BioEconomy (KBBE)

Page 6: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Key drivers from industrial perspective

Source: OECD “The Bioeconomy to 2030: designing a policy agenda”

Social, economic and technological factors will create

new business opportunities for biotechnology,

requiring new types of business models.

En Route to the Knowledge Based BioEconomy (KBBE)

Page 7: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

En Route to the Knowledge Based BioEconomy (KBBE)

Think about…

Enabling Technologies

EXAMPLE: Technology-Push for novel Products

Novel Taste Modifier for Food Industries

Reduction of unhealthy food ingredients like sugar, salt, fat,…

Page 8: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 8

Food industry in the press

Page 9: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 9

Food industry in the press

The Extraordinary Science of Addictive Junk Food (Michael Moss)

NATURE (2012)

The Lancet (2013)

Page 10: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 10

Chemoperception

Example: Novel natural sweetener / sweet enhancer

Smell

Sight

Balance Haptics

Skin Sensation

Taste

Hearing

Human Exteroceptive Senses

Page 11: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 11

Human sensation has been identified to the molecular level

by discovery of corresponding receptors

Human sweet taste receptors

T1R2 & T1R3

have been identified

and can be used as

molecular screening tools

loc

atio

ns

of h

um

an

tas

te re

ce

pto

rs

Example: Novel natural sweetener / sweet enhancer

Page 12: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 12

human

cell line

GPCR-R2

Fluorescence detection

of intracellular calcium level

Activated

heterodimeric GPCR

Calcium detection

via fluorescence

Cell Based Assay

Fluorescence

GPCR-R3 ligand

Example: Novel natural sweetener / sweet enhancer

Page 13: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 13

Example: Novel natural sweetener / sweet enhancer

Page 14: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 14

Next level technology: Human taste cells

sour

sweet umami salty

bitter

stem

support

Page 15: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 15

natureOUTLOOK (2012)

Fungiform papillae

Next level technology: Isolation of human taste cells

In cooperation with

Page 16: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 16

Isolation and programming of dedicated taste cell lines

bitter ScreenlineTM

sour ScreenlineTM

sweet ScreenlineTM

umami ScreenlineTM

salty ScreenlineTM

Page 17: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 17

Proliferating human taste cell lines

ScreenlineTM HTC-8

Page 18: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 18

En Route to the Knowledge Based Bio-Economy (KBBE)

Think about…

Enabling Technologies

EXAMPLE: Expanding feedstock range beyond corn, …

Feedstock

Page 19: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 19

Acidianus ambivalens Sulfur Oxygenase/Reductase (SOR)

Courtesy

Tim Urich,

Science 2006

Page 20: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 20

A fully integrated nanoscale chemical plant Metabolism facts

Photo

: W

. Z

illig

Acidianus ambivalens

• Obligate Chemolithoautotrophic Metabolism

• Topt 80 °C; pHopt 2,5

• Sulfur metabolism as sole energy source

• alternative anaerobic or aerobic metabolism

• e--donators: H2, S˚, e--acceptors: O2, S˚

• fully autotrophic :

CO2 fixation as sole carbon source for all syntheses

collaborative genome project

BRAIN AG, TU Darmstadt

Zentrum für molekulare Evolution und Biodiversität

Max Planck Institut für Biochemie

Universität Tübingen

1

1 µm

Biosynthetic creativity: the Acidianus ambivalens example

Page 21: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 21

Changing feedstock from fossil to …

Molasses

Starch

hydrolysates

Crop Silage

Production of biobased

Biotransformation / Biocatalysts

wildtype or engineered enzymes and microorganisms

producing primary/secondary metabolites

or producing non-natural chemicals

Sugars Chemicals

fine / specialty /bulk

Materials /

Bioplastics

Energy sources /

Biofuels

. . .

Renewable Feedstock

Glycerol

Prom enzyme1 enzyme2 enzyme3 enzyme4

Page 22: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 22

Changing feedstock from fossil to …

Molasses

Starch

hydrolysates

Crop Silage

Production of biobased

Biotransformation / Biocatalysts

wildtype or engineered enzymes and microorganisms

producing primary/secondary metabolites

or producing non-natural chemicals

Sugars Chemicals

fine / specialty /bulk

Materials /

Bioplastics

Energy sources /

Biofuels

. . .

Renewable Feedstock

Glycerol

Prom enzyme1 enzyme2 enzyme3 enzyme4

Ligno-

cellulose

Waste streams

CO2

Page 23: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 23

Niederaußem

The Microbiological Carbon Capture Concept

Page 24: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 24

Rational Bioprospecting: Microbial Life in Flue Gas Tracts

Page 25: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 25

Example: Microbial production of Lactate using CO2 as feedstock

LDH

NADH

COOH

|

CH-OH

|

CH3

Lactic acid

• Microorganism with reductive citric acid cycle

as a chassis

• add Lactate-Dehydrogenase

• Provide 1 Redox-equivalent NADH from cellular metabolism

PLA

Products from CO2 as a feedstock

Page 26: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 26

En Route to the Knowledge Based Bio-Economy (KBBE)

Think about…

Enabling Technologies

EXAMPLE: Building-up value chains for biotech ingredients for cosmetics

Feedstock

Value chains

Page 27: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

The chemical product value chain is complex R

aw

Mate

rials

/ F

eed

sto

ck

Chemical Industry

Supplier Industries, Biotech Industry

Research Institutes

Diversified Consumer Product Industries

Product

VI

Co

nsu

mer

Mark

ets

Product

IV

Production

Product

II

Registration

Sales

Production Registration

Sales

Production Registration

Sales

Raw

Material

Sales

Page 28: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Building up value chains

e.g. for novel cosmetic ingredients

BRAIN AG, Zwingenberg

Producer Strains

Enzyme Technologies

BioActives

Page 29: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

B2C Markets

Retail, Perfumeries,

Cosmeticians/studios

• R & D

• IP, Legal, Registration

• Efficacy testing

• Inlicensing

L.A. Schmitt, Ludwigstadt

MONTEIL GmbH, Oestrich-Winkel

Mekon Science Networks, Eschborn

B2C Markets

Direct Marketing,

WebShop • Marketing

• Sales, Logistics

• CRM, PR

• Marketing

• Sales, Logistics

• CRM, PR

• Production kg-ton scale

• Packaging

• Formulation

• Stability / Safety

100%

100%

JV

Building up value chains

e.g. for novel cosmetic ingredients

BRAIN AG, Zwingenberg

Producer Strains

Enzyme Technologies

BioActives

Page 30: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Building up value chains

e.g. for novel cosmetic ingredients

Page 31: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0 31

En Route to the Knowledge Based Bio-Economy (KBBE)

Think about…

Enabling Technologies

EXAMPLE: Network-Organisations, Clusters, …

Feedstock

Value chains

Structures

Page 32: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Structure of New Organisations in Industrial Transformation

“The meaning of the horizontal corporation within the informational/global

economy is as a “NETWORK ENTERPRISE“. Corporations can be distinguished

here between STATIC and EVOLVING organizations. The first type has as its goal

self-reproduction. In the second type, the organization's goals lead to endless

structural changes. I call the first type of organizations bureaucracies; the second

type enterprises".

Prof. Dr. Manuel Castells

University of California, Berkeley

Department of City and Regional Planning

Berkeley's Center for Western European Studies

The Information Age: Economy, Society, and Culture,

The Rise of the Network Society, The Information Age: Economy, Society and Culture, Vol. I. M. Castells (1996).

Cambridge, MA; Oxford, UK: Blackwell, 556 pp., ISBN 1-55786-617-1

The Power of Identity, The Information Age: Economy, Society and Culture, Vol. II. M. Castells (1997).

Cambridge, MA; Oxford, UK: Blackwell, 461 pp., ISBN 1-55786-874-3

The End of the Millennium, The Information Age: Economy, Society and Culture, Vol. III. M. Castells (1997).

Cambridge, MA; Oxford, UK: Blackwell, 418 pp., ISBN 1-55786-872-7

Page 33: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Vertical/Horizontal Organization Network Organization

A network organization is complex but could be more efficient

Page 34: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Structure of New Organisations in Industrial Transformation

Hallmarks of growth:

(1) One hallmark was the much-heralded transition from mass production to flexible

production, or from 'Fordism' to 'post-Fordism'.

(2) Another is the "crisis of the large corporation, and the resilience of small and medium firms

[SME's]….".

(3) A third is a new style of management, most evidently around the Japanese practices that

reduce uncertainty by opening up communication between workers and management, and

between suppliers and customers.

(4) a variety of networked relationships among SME's

(5) various practices large corporations use to subcontract and license production to smaller

firms.

(6) the "intertwining of large corporations in…strategic alliances“

Prof. Dr. Manuel Castells

University of California, Berkeley

Department of City and Regional Planning

Berkeley's Center for Western European Studie The Information Age: Economy, Society, and Culture,

The Rise of the Network Society, The Information Age: Economy, Society and Culture, Vol. I. M. Castells (1996).

Cambridge, MA; Oxford, UK: Blackwell, 556 pp., ISBN 1-55786-617-1

The Power of Identity, The Information Age: Economy, Society and Culture, Vol. II. M. Castells (1997).

Cambridge, MA; Oxford, UK: Blackwell, 461 pp., ISBN 1-55786-874-3

The End of the Millennium, The Information Age: Economy, Society and Culture, Vol. III. M. Castells (1997).

Cambridge, MA; Oxford, UK: Blackwell, 418 pp., ISBN 1-55786-872-7

Page 35: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Capital, Investments

Entrepreneurs

People, Inventors, Visionary, Dreamer, …

Structures, organsizing a dynamic interfaces between Research

Institutes, Biotech Companies, Big/Consumer Industries

(don´t forget politics and public perception… !)

What we need …

Enabling a knowledge-based Bioeconomy

Page 36: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

not an easy task

a competitive Strategy II: Chance for new Business and new Industries

a strategic Investment

a competitive Strategy: Chance for Germany as a industrial location

Bioeconomy is….

Enabling a knowledge-based Bioeconomy

Page 37: Enabling a Knowledge-Based Bioeconomywildtype or engineered enzymes and microorganisms producing primary/secondary metabolites or producing non-natural chemicals Sugars Chemicals fine

Engineering Biology.

© BRAIN Aktiengesellschaft Zwingenberg Germany www.brain-biotech.de +49 (0) 6251-9331-0

Thank you for your attention

BRAIN Aktiengesellschaft

Darmstädter Straße 34-36

64673 Zwingenberg

+49 (0) 6251-9331-0

www.brain-biotech.de

[email protected]

Dr. Jürgen Eck