REPORT

Biotechnology: from Innovation to Industrial Production

On 10th May 2017, the VIB International Plant Biotechnology Outreach organized the 3rd IIBN Forum on

“Biotechnology: from innovation to Industrial Production”. The forum was an outstanding occasion to

bring together over 90 experts from the public and the private sectors in the area of biotechnology. They

discussed diverse eco-efficient bio-processes and renewable biological resources which are creating new

value chains in an emerging knowledge-based bioeconomy. Examples that are or are nearly on the market

were presented to clarify the timeline, costs and technical processes needed to bring a product on the

market. The focus was to promote value creation beyond food production to support sustainable

development in Africa and other developing countries. The International Industrial Biotechnology

Network (IIBN) is an international network created under the impulse of UNIDO and financed by the

Flemish government. It fosters sustainable applications of biotechnology for innovative farming and

inclusive industrial development with a focus on low and middle income countries. By catalyzing synergies

and partnerships, IIBN augments international cooperation opportunities, leverages resources, and

attracts investments in R&D and capacity building.

Yvonne Lokko from the United Nations Industrial Development

Organization UNIDO introduced the role of biotechnology in industrial

development and the key challenges the world is facing today. The

important contribution of inclusive and sustainable industrialization in

helping Africa to overcome its critical development challenge is clearly

recognized in the 2030 Agenda for Sustainable Development. The

Sustainable Development Goal 9 (SDG 9) calls to build resilient

infrastructure, promote sustainable industrialization and foster

innovation. Achieving this goal will require a broader range of

resources than any individual entity can provide, highlighting the

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importance of multi-stakeholder’s

partnerships. New forms of Public-

Private Partnerships and financing will

facilitate the establishment of industries

in developing countries. Biotechnology

industry is a key driver in helping to achieve the SDG 9. Relevant in key economic sectors such as

agriculture, health, manufacturing and energy, Dr Lokko concluded that it has a role to play at every steps

of the value chain and provides opportunities for progress towards the achievement of global

competitiveness in developing countries.

Matin Qaim, Professor of International Food Economics and Rural

Development at the University of Göttingen, put into perspective the

potential of genetically modified GM crops to contribute to food security and

sustainable agricultural development. Today, there are only 2 modified traits

on the market: herbicide tolerance and insect resistance. Over the last 20

years, many impact studies were carried out on these 2 traits focusing on

different countries and crops, with different types of data and

methodologies, and also generating different results. Meta-analysis of GM

crop impacts can be useful to draw broader lessons from the cumulative

evidence and to explain the reasons for heterogeneity in the impacts. The

analyses show significant increase in crop yield, significant reduction in

pesticide use, significant increase in farmer profit and household living

standard, and reduction of environmental and

health effects. Future GM traits could be much

more beneficial: drought-, salt-, heat-tolerance,

nitrogen use efficiency have all been already tested in the field. However, the

question is whether these technologies will ever be taken to the commercial

stage and whether farmers will ever grow the improved crops. Effects of GM

over-regulation fuel public perception that GM crops are dangerous, they

make the technology unnecessarily expensive, contribute to industry

concentration and to a focus on large countries as well as on traits of large

commercial interest. Prof. Qaim concluded that GM crops are not a panacea

for solving all the problems in the world. However, without modern plant

science and breeding, sustainable development will hardly be possible. The combination of different

breeding tools (incl. conventional techniques) can help to provide solutions to many global challenges.

Nico Callewaert from VIB UGent Center for Medical Biotechnology is

developing innovative molecular technology to enable novel approaches

to the study, diagnosis and treatment of disease as a rapid response to

emergent epidemics. He demonstrated how glycosylation is a major

deciding factor in biopharmaceutical expression system choice.

Glycosylation is inherent to protein production in eukaryotes and makes

glycoprotein drug production complex. Heterogeneity in the N-glycans on

therapeutic proteins causes difficulties for protein purification and process

reproducibility and can lead to variable therapeutic efficacy. Prof.

Callewaert’s research group developed the GlycoDelete technology to

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solve plant glycan allergenic/immunogenicity problem. This technology could lead to more consistent

performance of therapeutic proteins and modulation of biopharmaceutical functions. Prof. Callewaert

pointed out the importance of seed based platforms (e.g. legumes seed). On the one hand, seeds allow

recombinant proteins to stably accumulate at a relatively high concentration for long periods of time. In

addition, within the compacted biomass, proteins are protected from degradation. On the other hand,

seeds can be stored in dried form for many years/decades and they keep their germination power. The

strategy is to have seed based platforms, use industrial biotechnology to produce flours containing the

protein, use existing pharmaceutical manufacturing technology and finally, purify the antibody and

produce the virus in about a week. This would allow a rapid response to epidemic outbreaks.

The international well-known expert in plant genetics and

biotechnology, Yuri Gleba, presented different plant-made

pharmaceuticals and bio-materials as novel industrial processes and

products relevant to developing countries. Several plant-made

pharmaceutical products already entered the market phase: e.g. non-

Hodgkin's lymphoma (NHL) vaccine, Influenza vaccine and anti-Ebola

monoclonal antibodies. Today, there is a large choice of industrial

production platforms such as: transfection using vacuum infiltration,

which is ideal for high-cost products (e.g. biopharmaceuticals, vaccines);

transfection using spraying Agrobacterium on plants, which is ideal for

low-cost products (e.g.

industrial enzymes, agronomic traits); a transgenic

version using spraying plants with ethanol inducible

amplification, which is ideal for high-volume products

(e.g. biomaterials, antimicrobials). There are also

promising novel antivirals for rapid responses during

outbreaks (e.g. Ebola, Zica). Plant-made vaccines are

inexpensive and so are ‘biobetter’ therapeutic

antibodies, making them interesting especially for developing countries. New product concepts are

emerging such as non-caloric natural sweeteners to replace sugar. For instance, thaumatin is a natural

source isolated from the Katemfe fruit grown in West Africa. It is 100,000 times as sweet as sucrose but

the production is still limited. Dr. Gleba concluded that only 5% of the global cultivated areas would be

needed to provide unlimited supply of recombinant Thaumatin.

Amandine Collado from Oxitec in UK introduced the audience to Oxitec solutions and more specifically

how from a laboratory the company went to a factory stage. Oxitec has the

aim of combating pests, but also disease vectors, through the reduction of

the pest populations, with a

genetic approach that is safe,

sustainable, economic and

applicable to many insect species

worldwide. Her presentation

concentrated on mosquitos and

the strategy developed by Oxitec

to limit their population (self-

limiting gene). Oxitec male

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mosquitos are produced for release. They mate with wild female. The offspring dies (both male and

female) through ‘genetic sterility’ before they can reproduce and transmit the disease. Within the same

self-limiting technology, a male-selecting strategy is developed where the self-limiting gene applies only

to female mosquitos. The male mosquitos survive in the progeny. The self-limiting gene stops the

mosquito from expressing essential genes. By adding the antidote Tetracycline through the diet in a

production environment, healthy and competitive male mosquitos can be produced. Dr. Collado

highlighted the efficiency of this industrial production, the quality controlled outputs and the production

of 60 million male mosquitoes/week.

Dirk Carrez, Executive Director of the Bio-based Industries Consortium,

outlined the importance of an innovative BioBased Economy in Europe.

The Bio-based Industries Consortium has been established in 2012 in

order to represent the private sector in the new Public-Private

Partnership BioBased Initiative BBI JU with the European Commission.

The objective of the BBI JU is

to develop new value chains

involving different industrial

sectors and create new

business opportunities for

biobased products in Europe.

Three types of projects are

funded by the BBI JU: (1) research and development projects;

(2) demonstration projects or proof-of-concept phase and (3)

flagship projects, which are full scale production plants. The

companies’ members of BIC covering diverse industrial sectors

(e.g. agriculture and agri-food, forestry and pulp/paper,

technology providers, chemicals and materials, energy,

aquatic, etc.) started to interact between each other. For

instance, the food industry is looking for opportunities to valorize and add value to their waste streams

and starts to collaborate with chemical industries, thus creating new value chains. Dr. Carrez concluded

that industries need large quantities feedstock at cheap prize. Today, industries see opportunities, for

instance, in Africa, where there is huge amount of feedstocks to be valorized in many different products

(bioenergy, biofuels and also other products) and, in this way develop new local value chains.

Wim Soetaert’s presentation

focused on “Industrial production of

Human Milk Oligosaccharides

through industrial biotechnology”.

InBiose is a company active in the

industrial production of speciality

carbohydrates, which are not used

as food (such as sucrose) or energy

source, but as active ingredients.

Speciality carbohydrates are rare in

nature and difficult or sometimes

impossible to produce.

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Consequently, they are expensive. They are used in many applications such as pharmaceuticals,

nutraceuticals, cosmetics, chemicals, plant protection. Carbohydrates consist of unconventional building

blocks, which can be assembled in very specific ways and produce, for instance, Human Milk

Oligosaccharides present in the mother’s milk but not in most other mammals’ milk. Inbiose uses an

integrated technology platform for high throughput development of speciality carbohydrate production

strains, from the metabolic engineering of the production organism, the development of the fermentation

process and its scaling-up, to the product recovery process and conditioning, up to the market. Once

produced, the objective of InBiose is to add the Human Milk Oligosaccharide to the cow’s milk so that it

looks “closest to breast milk”.

Rudy Parton, Chief Scientific Officer of GF Biochemicals, provided an

overview of “Levulinic acid and derivatives: sustainable solutions for today

and tomorrow”. He presented different approaches to bring levulinic acid to

the market. Levulinic acid is today used for new building blocks to improve

performance. It has large potential and broad application across a range of

market segments such as personal care, agrochemicals, fragrances,

household and industrial

cleaners. A new biochemical

brought to the market needs

to have better performance,

higher value than existing products, and competitive

price. For instance, Levulinic Ketal Polyols for

Polyurethane Foam Applications offer better performance

and more versatility versus other bio-based alternatives

(seed-oil polyols such as castor oil). Dr. Parton concluded that levulinic acid has huge potential in the

development of a biobased chemical industry.

Johan Thevelein, Chief Scientific Officer of GlobalYeast, discussed “The role

of GlobalYeast in the world-wide transition to a sustainable bio-based

economy”. GlobalYeast is a Belgian-Brazilian start-up company founded in

2015. Its mission is to develop superior industrial yeast strains for the

industrial production of bioethanol and bio-based chemicals from renewable

resources, either sugar or biomass, using cell factory micro-organisms such

as yeast. For first-generation feedstocks (mainly food crops), commercial

yeast strains for industrial fermentations are well-established and have

mature markets. For second-generation feedstocks (mainly waste streams

and energy crops), yeast

strains cannot naturally

utilize pentose sugars

present in lignocellulosic biomass. GlobalYeast developed

second-generation industrial yeast strains with excellent

performance in concentrated lignocellulose hydrolysates.

Looking at the growth drivers of the bioethanol industry

(mainly climate change and energy security), GlobalYeast

plays and will continue to play a significant supporting

role in the transition to a biobased economy.

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Marc Van Montagu concluded the conference by raising the attention to

the place of science in society. Why is society afraid of science? Our

knowledge of the molecular basis of plant growth and development has

progressed tremendously since plant gene engineering became a routine

technology, around 30 years ago. Even though technological innovations

are promising, their applications are not straightforward today. The

discovery of Genetically Modified (GM) crop biotechnology in the 80s led

to a series of technological inventions that opened a wide spectrum of

agricultural and

industrial applications.

The innovation has

triggered one of the

largest changes in the history of agriculture, yet it has

faced an extremely hostile response to

commercialization. It is the duty of all scientists to do

a major effort to understand better the fear of society

for new knowledge and the innovative applications

resulting from this knowledge. Prof. Van Montagu

recommended that science departments should

introduce the coming generations to cognitive sciences and responsible decision making including social

and emotional learning.

The IPBO team thank all the speakers and all the participants for their contributions, which made this

event a major success. The conference programme and all the presentations can be found here:

http://ipbo.vib-ugent.be/events/iibn-forum-2017.

For further information on IPBO and IIBN, do not hesitate to contact the IPBO team here: ipbo@vib-

ugent.be.