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Genetically Modified Organisms for Bulk Chemical Production

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Title: Genetically Modified Organisms for Bulk Chemical Production


1
Genetically Modified Organisms for Bulk Chemical
Production
  • Leo van Overbeek

2
Outline presentation
  • Introduction
  • Risk evaluations
  • White and Green biotechnology for bulk
    chemical production
  • Bulk chemical production in the future
  • Conclusions

3
Background
  • Research at Plant Research International,
    Wageningen
  • Construction of genetically modified plants
    disease suppression, qualitative aspects,
    optimization (marker-free GM plants)
  • GMO acceptance (reports, discussions)
  • Soil biology (GMO impact analysis)

4
Introduction
  • Bulk chemical production
  • E.g. Polyhydroxyalkanoate (PHA)
  • Production by making use of Genetically Modified
    Organisms (GMOs)
  • Optimal yield
  • Chemical modification
  • White Biotechnology (contained use) and Green
    Biotechnology (GM plants in open fields)

5
Goal
  • Overview of prospects and limitations in the
    application of GMOs for bulk chemical production
  • Emphasis on
  • White Biotechnology
  • Effects on nature and food chains
  • Knowledge gaps for future (large quantity)
    production

6
Risk evaluation and public perception
  • Release of GMO will always occur
  • What are the events after GMO release
  • In order of severity
  • Effect (neutral)
  • Hazard (negative consequence)
  • Risk (impact)
  • Risk assessment
  • Risk chance of hazard x exposure (volume/ time)
  • Public perception on modern biotechnology
    (occasionally no rational arguments used in
    discussions)

7
Non-rational arguments
  • Field experiment with a GM potato line
  • Aimed to establish possible effects on the
    indigenous soil and plant-associated microflora
  • Field destroyed by activists

8
From literature
  • Field release studies with GM bacteria and plants
  • GM plants and micro-organisms are constructed to
    demonstrate an effect (worst case)
  • No effects observed
  • Or only transient effects observed
  • No obvious hazards could be find in literature!

9
Use of GMOs for bulk chemical production
  • Effect on food chains
  • PHA is non-toxic and non-allergenic
  • Effects on natural environments
  • PHA is biodegradable
  • No impact on consumption goods and natural
    environments expected!

10
GMO effect after release
Effect Measure
Recombinant gene expression Controlled regulation of recombinant gene construct
GMO survival and spread Physiologically impaired host (e.g. auxotrophic strains) Containment genes
Gene transfer Recombinant DNA insertion in non-mobile constructs
Gene type Genes whose products do not have obvious effects on other organisms Assessment for genes whose products have an effect
11
Limitations to evaluate consequences of GMO
releases
  • Analytical tools
  • Technical limitations for detection
  • Environmental impact
  • Where to compare with?
  • Natural fluctuations are large and not always
    understood
  • Ecology
  • Not all organisms are described (soil)
  • Not all interactions are clear

12
White Biotechnology
  • Contained use of micro-organisms (or
    biotechnological derivatives) for production of
    e.g. enzymes and bulk chemicals
  • Use of renewable raw materials and advanced
    enzyme systems, replacing fossil raw materials
  • bio-energy
  • biomaterials
  • bulk chemicals
  • Direct e.g. bulk chemicals like PHA
  • Indirect production of enzymes required for bulk
    chemical production
  • Realistic for industry

13
PHA production in closed systems
Construct Reference
Ralstonia eutropha with phaC from Aeromonas punctata Fukui and Doi 1997 and 1998.
Aeromonas hydrophila with yafH from E. coli Lu et al., 2004
A. Hydrophila with phaPCJ genes from A. punctata Han et al., 2004
Arxula adeninivorans with phbABC genes from R. eutropha Terentiev et al., 2004
14
Recommendations for white biotechnology
  • Microbial host
  • Suitable for optimization (growth properties,
    nutrient requirements)
  • Containment (loss of viability after release)
  • Recombinant gene
  • Possibilities for modification of the product
  • Control on gene regulation
  • Containment genes (killing of host after
    accidental release)
  • Waste
  • Other applications
  • Eradication of living GMOs in waste products

15
Green Biotechnology
  • Genetically modified plants in fields
  • Open production facilities
  • Possibility of free exchange of GM materials with
    the environment and food chains
  • Coexistence between agricultural systems
    (controversy organic conventional farming)
  • Lower emphasis for industry

16
PHA production by plants
Construct Reference
Flax (Linum usitatissimum) with phbABC genes from R. eutropha Wróbel et al., 2004
Tobacco (Nicotiana tabacum) with phbABC genes from R. eutropha Arai et al., 2004
17
Requirements for Green biotechnology
  • Plant host
  • Choice of best performing crops for bulk chemical
    production
  • Preference for non-food crops
  • Recombinant gene
  • Marker-free constructs
  • Restrictions on sexual exchange of rec DNA (e.g.
    plastid transformation)
  • Logistics to keep GMO seeds separated from
    non-GMO seeds

18
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19
Bulk chemical production
  • Application of GM microbes for bulk chemical
    production under contained conditions is
    realistic
  • Safe production
  • Containment guaranteed
  • Applications of GM plants in open fields is
    uncertain and thus less realistic
  • Containment in open fields is difficult to
    maintain
  • Post harvest measures are required (transport,
    storage, raw material treatments)

20
Prospects
  • White biotechnology will become important for
    bulk chemical production
  • Production with GM micro-organisms in closed
    reactors will largely increase
  • Risk assessment must be adapted for larger-scale
    production facilities
  • Processing of fermentation waste products will
    become important

21
Expected scale enlargement
White Biotechnology
Environmental-friendly production
Adaptations Production facilities Biological
containment
Wastes
time
22
Consequences
  • Increased biotechnological production means
  • Less chemicals and energy required
  • Less toxic wastes produced
  • More emphasis on containment
  • Infrastructure (input raw materials, processing)
  • Biological containment (facilities and
    constructs)
  • Increased organic waste from reactors
  • Concern for living GMOs in products made out of
    waste

23
Solutions
  • Technical improvement of production facilities,
    circumstances and GMO constructs
  • Alternative use of waste from fermentation
    reactors
  • Agricultural use e.g. by composting and heat
    inactivation or recycling of waste compounds

24
Conclusions
  • Only temporal effects have been observed in
    small-scale GMO release studies
  • GM constructs for bulk chemical production must
    be qualified as low in risk
  • No effect can be expected with the application of
    GM microbes for bulk chemical production in
    white biotechnology
  • Uncertainties exist with increased scale and
    long-term production with GM plants
  • Waste products from fermentation reactors must be
    processed and free of living GMOs

25
Knowledge gaps
  • Present analytical tools may be too limited to
    detect effects by increased-scale and long-term
    production special emphasis on GM plant
    production
  • Ecological baseline knowledge to discriminate GMO
    from non-GMO effects
  • Relevant information on ecological interactions
    between species (e.g. what can be the effect of
    elevated levels of PHA on different populations)
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