NATIONAL RURAL ISSUES Transformative Synthetic …...The economic potential of the technology is significant, with a BCC Research report stating that the global synthetic biology market

NATIONAL RURAL ISSUES

Transformative technologies

A fact sheet series on new and emerging transformative technologies in Australian agriculture

Synthetic biology

� Synthetic biology provides new insights into biological structures that will inform a range of applications to agricultural science.

� It will enable scientists to engineer biological organisms and systems beyond those possible with existing biotechnologies.

� Applications could include new control measures for pests and diseases, new crops, green fuels, and environmental and food processing monitors.

� The social acceptability of engineered and manipulated biological organisms involved in food production may be a challenge for food industries.

� Biosafety, biosecurity and ethical issues are the most significant policy and regulation issues raised by the use of synthetic biology.

Snapshot

Synthetic biology is the deliberate design of biological systems and living organisms using the principles of engineering. It provides a better understanding of the biological world, to reconstruct or redesign biological systems or parts for a particular purpose.

Synthetic biology combines aspects of biology, genetics, chemistry, engineering and computer

science to create fully operational biological systems. There are two overarching methods

applied in synthetic biology: the top-down approach modifies existing organisms, genes

and enzymes within biological material; and the bottom-up approach seeks to create novel

biochemical systems and organisms from scratch. Both approaches aim to engineer organisms

or new biological systems that are not found in nature to generate useful chemicals from

inexpensive and renewable sources.

Common and simple organisms like yeast and bacteria can be engineered by synthetic

biologists to effectively work as biological factories, producing a range of different chemicals

through fermentation. The chemicals may range from low value fuels, commodity chemicals

and specialty chemicals through to high value pharmaceuticals.

Synthetic biology is regarded as more sophisticated than other biotechnologies, such as

genetic engineering and gene editing, but the knowledge gained through synthetic biology

can be applied to the development of practical tools and techniques for use in existing

biotechnologies. Synthetic biology also converges with nanotechnology, as the modification

and creation of molecules, genes and enzymes occurs at the nanoscale.

As a new technology, synthetic biology can be applied to many industries, including fuel,

agriculture, food, manufacturing, cosmetics and medicine. However, a range of regulatory

and ethical issues needs to be addressed before the benefits of synthetic biology are realised.

A fact sheet series on new and emerging

transformative technologies in Australian agriculture

Agricultural applications

Photo - GO Resources

There are many novel and potentially useful applications of synthetic biology, including the economic production of anti-malarial drugs, the production of ‘green’ fuels and the creation of programmable cells to treat cancer.

The economic potential of the technology is significant, with a BCC Research report stating that the global

synthetic biology market was worth US$2.1 billion in 2013 and is expected to grow to US$11.8 billion by 2018.

Synthetic biology is the cornerstone of the growing ‘green chemical’ industry, which is predicted to reach

22% of the trillion dollar global chemical market by 2025.

Modifying and creating new systemsSynthetic biology provides a deep understanding of complex living organisms at a molecular level, giving

scientists the knowledge to build up or strip down biological systems to their basic building blocks.

With in-depth knowledge of the genetic structure of plants, synthetic biology enables the development of new

plant varieties from the ‘top down’ by changing large clusters of genes and gene parts, rather than modifying

one or a few genes as is the approach of genetic engineering (or GM). For example, more sophisticated crops

could be developed to grow in changing climates, such as crops that produce more nutritious grain and crops

able to cope with both drought and frost. Crops that sense and respond to their environment also could be

possible, through biosensors and genes that switch on or off in response to certain conditions.

A global consortium, including Macquarie University and the Australian Wine Research Institute, is constructing

a synthetic version of the yeast genome from the ‘bottom up’. The synthetic genome will enable researchers

to learn about its fundamental properties and components. The yeast research is invaluable to agriculture and

many other industries, as yeast is one of the pre-eminent candidates for industrial fermentation, which will

be the source of many synthetic biology products across many industries.

Applications of synthetic biology to the agricultural supply chain are wide ranging, from individual crops,

production systems and farm management to food production.

Advancing pest controlEngineered insects have been created for pest control using synthetic biology and advanced genetics. A UK

company has inserted a self-limiting gene into mosquitoes to control dengue fever. In the wild, the insect’s

offspring inherit the gene and die before they reach adulthood, causing wild populations to decline by up

to 90%. In the laboratory, the self-limiting gene can be turned off with an antidote to enable further production

of the engineered insects. The company’s technology also can be applied to agricultural insect pests such as

fruit flies and bollworm, as part of integrated pest management.

Producing alternative inputsThe steady rise of antibiotic resistance is a cross-industry problem, which is demanding an alternative technology

to treat infection and disease. A US company is using synthetic biology to engineer highly precise antimicrobials,

called ‘eligobiotics’, which can be programmed to eliminate bacteria based on the genetic sequences the

bacteria carry in their genome. The eligobiotics can be formulated to eradicate the harmful bacteria whilst

sparing the beneficial bacteria. The technology has application to health, cosmetics, food and agriculture.

Designing crops for fuel productionSynthetic biology offers potential in the development of sustainable fuels, with agricultural crops being an ideal

feedstock. Australia is leading the move from fossil fuels to renewable feedstocks with the development by

CSIRO of super high oleic safflower. The ‘super high’ oil levels that have been synthetically engineered in

safflower will yield sufficient oil to replace some petrochemicals in the manufacture of plastic, paints, resins

and other industrial oils.

3


Synthetic biology

Transforming agriculture

The impact of synthetic biology on agriculture is wide reaching, complex and groundbreaking. The technology introduces processes, organisms and products that one decade ago were thought not possible.

Synthetic biology is a new technology and currently, its value to agriculture is as much in the knowledge

it creates about biological systems, as it is in the products and devices that can be developed using that

knowledge. The potential for synthetic biology to converge with other technologies, notably nanomaterials

and bioengineering, further increases its transformative power on agricultural production systems, food quality

and industry resilience.

Solutions and opportunities The landscape of agriculture will be transformed by crops and animals adapted to new growing conditions

and meeting new market specifications. The products and processes of synthetic biology will provide solutions

to maintain agricultural production in a changing climate, characterised by more extreme weather events. The

same developments will help Australian farmers meet the challenge of the accelerating global demand for food,

not only for sustenance in poor populations but also to meet the aspirations of increasingly affluent consumers

in Asia and India. Synthetic biology also will provide new markets for farmers, beyond food and fibre, such as

the development of crops to produce super high oil levels, for industrial purposes.

Detection of safety and qualityAgriculture, as with other industries, presents some risk of contamination of food products and production

environments. Biosensors will improve food safety and natural resource management with more precise

and timely detection of contaminants, than current monitoring methods. Such potential has been realised

with the CSIRO construction of the CYBERNOSE® sensor, which places a protein that replicates the highly-

developed smell receptors of the nematode into yeast or bacteria. The sensor changes shape when a

certain molecule binds to it, and emits a mixture of blue and green light indicating the presence of particular

substances. CYBERNOSE can be used to detect toxins or contaminants in food; it also can be used to verify

provenance and monitor the raw ingredients of foods and beverages.

Non-traditional food sourcesIn response to cost, scarcity or ethics, synthetic biology offers new ways of producing existing foods. Although,

the transformation from agricultural production to factory production, for some foods, may challenge traditional

ideals of food production. Currently, a Swiss company is engineering yeast to produce the key flavour and colour

compounds of saffron, one of the world’s most expensive spices. Synthetic production of saffron via fermentation

significantly reduces production cost of the product and ensures a stable supply. In response to demand by

consumers who seek ‘animal-free’ or non-allergenic food, a US company is developing cow-free milk by inserting

certain DNA sequences from cattle into yeast cells. After a few days of culturing, the cells produce milk protein,

which is combined with fats sourced from vegetables to produce lactose and cholesterol-free milk.

New knowledge and careersSynthetic biology will advance the knowledge and understanding of science more than has been possible with

previous biotechnologies. The discipline is already providing more information about how DNA, cells, organisms

and biological systems operate. Synthetic biology will create new skills and careers throughout the agricultural

supply chain, from research and development where new systems are designed, to manufacturing where new

materials are created and used to produce new products.



Manipulating plant production with synthetic biology

Producing and using plant hormones, with the help of synthetic biology, will provide opportunities to manipulate crop nutrient uptake and reduce nutrients applied as fertiliser; or influence plant development such as shoot tip growth in fruit trees to optimise number and size of fruit produced.

The issueDriving the research interests of Dr Claudia Vickers

and her group at the University of Queensland’s

Australian Institute for Bioengineering and

Nanotechnology is the need for more sustainable

and environmentally friendly approaches to farming

and industrial activities. In particular, she has an

interest in using biology to replace industrial practices.

Claudia’s group is using synthetic biology to capture

and enhance the benefits of compounds naturally

produced by plants, such as hormones.

The group is interested in an abundant and diverse

group of compounds called isoprenoids. Isoprenoids

are involved in the way plants interact with the

environment, and they affect growth, contribute

to some pigments and occur in some of the

essential oils.

Of particular interest, are the isoprenoid-signalling

compounds in the class of hormones called

strigolactones. Strigolactones are highly active in

plants at tiny concentrations. They have two main

roles: controlling plant development and as root

exudates to promote symbiotic interactions between

plants and soil microbes.

“By harnessing strigolactone and producing it

synthetically we can modulate economic aspects

of plant production.”

The technologyClaudia’s laboratory uses the ‘bottom up’ approach

to synthesise isoprenoids of interest, including

strigolactones. Applying the principles and tools

of synthetic biology, the researchers take genes

from plants and create metabolic pathways in yeast

to produce strigolactone through fermentation.

These pathways are modelled on naturally-occurring

processes in yeast, but with human intervention,

the function and production of strigolactones can

be up-regulated or super-charged.

Understanding the movement of organic carbon

through the pathway (carbon flux) and how it

influences strigolactone production is fundamental

to the process. A source of carbon is essential to

the process and Claudia’s group is interested in

using sucrose from sugarcane as a feedstock for

the yeast in this process, as sugarcane is readily

available in Australia.

“We have reconstructed synthetic pathways with

improved flux in yeast and are now examining

approaches to minimise carbon loss to competing

pathways, redirect carbon into pathways and

scavenge carbon lost to nonspecific reactions.”

Integral to her group’s work for the application

of synthetic biology to both microbes and

plants are sophisticated bioengineering tools

such as transformation vectors, expression control

systems, chromosomal integration systems and

reporter systems.

Synthetic production of

plant hormones enables more

precise control of economic

aspects of crops, such as

managing shoot tip growth

for uniform fruit size.


Synthetic biology

5


Synthetic biology

Case study

Contact detailsDr Claudia Vickers

Australian Institute for

Bioengineering and

Nanotechnology, University

of Queensland

E: [email protected]

T: +07 3346 3958

Photo - Joe Vittorio

The benefitsSynthetic biology provides a way for Claudia

to follow her goal to make farming systems

and industrial activities more sustainable and

environmentally friendly.

“Strigolactone is involved in both above and below

ground developmental pathways in plants. Through

its synthetic production and application to a wide

range of field and horticultural crops we can control

many aspects of plant development such as shoot tip

growth in apples to influence apple number and size,

shoot number in cereal crops and tree branching,

height and girth to produce better quality timber. By

artificially producing the hormone through synthetic

biology we have an economic means of producing

the compound, which can then be sprayed on plants.

“Being able to more precisely control plant growth, for

example, fruit production, makes for a more uniform

product, improved efficiencies and much less wastage.

“Through controlling root exudates we can manipulate

beneficial relationships between plants and bacteria or

fungi such as rhizobium that fix atmospheric nitrogen

and mycorrhizae that can aid phosphorus uptake by

plants. If we have a sustainable way of manipulating

plants so they can become more self-sufficient in the

provision of their nutrition it has got to be better for

our environment and resources use.

“Stimulating plants to form more prolific relationships

with mycorrhizal fungi will result in more effective

scavenging for nutrients in the soil and less reliance

on applied fertilisers, a major cost in plant production

systems.

“Additionally, if we use an Australian-produced

feedstock, like sugarcane, for the production of

strigolactone it will value add to an Australian industry.”

The futureClaudia explained that the application of synthetic

biology is restricted by the current level of scientific

understanding.

“Our knowledge pool is rapidly expanding, but we

need to ensure both the knowledge and tools are

widely accessible to advance the use and adoption

of this technology. We also need to ensure an

ongoing conversation at all levels of the community,

so the public is informed and engaged with the use

of the technology, especially as they are involved in

much of the funding through government support.”

Claudia predicts a future where we see a vast array

of products produced in an environmentally friendly

and controlled way through fermentation using

synthetic biology approaches, directly converting

sunlight, methane or waste products into

economically significant products.

Synthetic biology will

generate products to reduce

wastage of farm produce

and provide methods

to convert methane and

waste into economically

significant products.



Challenges for adoption

Synthetic biology is a rapidly developing science and many challenges that arise relate to technical aspects of research and development. However these are quickly overcome with progress and breakthroughs.

The main challenges facing the adoption of synthetic biology are issues such as unexpected complexity,

scalability, lack of tools, and ethical issues surrounding the manipulation of the biological world.

Unexpected complexityAs the science of synthetic biology develops, researchers are learning that naturally-occurring biological

systems are far more complex than originally thought. Further investigation has been required to understand

how synthetic organisms survive in natural environments, compared with their natural counterparts; and

how they may grow and evolve in natural environments.

Scalability of the technologyScalability is the major issue limiting the commercial adoption of processes developed by synthetic biology.

Currently, many processes are successful at a laboratory scale, however, at a commercial scale, a considerable

quantity of biological material is required for the process but is unavailable, especially for biofuels. As awareness,

interest and investment in the technology increases it is likely that this issue will be suitably addressed.

Gap between tools and applicationProgressing from a conceptual design of a biological function to a practical application presents significant

technical challenges, with access to required tools and materials often a limiting factor. This has been

addressed, in part, by the BioBricks Foundation, with its mission to ensure that the engineering of biology

is conducted in an open and ethical manner to benefit the people and the planet. The foundation provides

standardised biological parts (marketed as BioBricks™) that are safe, ethical, cost effective and publicly and

globally accessible. For the adoption of synthetic biology to expand, this sort of research support will need

to continue and evolve with the knowledge base of the technology.

Social and ethical challengesSynthetic biology is an avenue for creating artificial life and thus, poses complex social and ethical

concerns. The scientific community understands that public attitude to synthetic biology will be based

on transparency of the research and engagement with the general public. This will be essential for the

public’s understanding of the technology and its applications.

7


Synthetic biology

Policy and regulation

Policy and regulations regarding synthetic biology are still being established, both globally and in Australia. Biosecurity and biosafety are significant issues; and public acceptance of engineered living organisms is yet to be tested.

In Australia, as at 2016, products derived from synthetic biology are regulated through the Office of the Gene

Technology Regulator (OGTR) and other regulators with complementary responsibilities, such as Australian

Pesticides and Veterinary Medicines Authority and Food Standards Australia New Zealand, under the Gene

Technology Act 2000.

During a review of the Act in 2012, the Department of Innovation, Industry, Science and Research and the

CSIRO identified potential regulatory difficulties for products derived by synthetic biology, and a risk that the

technology was outpacing regulation. The Gene Technology Ethics and Community Consultative Committee

of OGTR has considered a number of regulatory issues regarding synthetic biology and maintains a watching

brief on developments. To date, the committee has concluded that synthetic biology does not raise new

ethical issues and should remain as part of the broader gene technology classification under the Act, and

subject to the same risk assessment processes.

The regulations of the OGTR and other federal regulators must also recognise the rights of state and territory

governments, under their own regulatory responsibilities, to designate zones for GM or non-GM crops for

marketing purposes. Under current arrangements this will also apply to products and organisms derived from

synthetic biology.

Regulation of R&D and commercialisation must ensure that biosafety and biosecurity are addressed. Concerns

about uncontrolled release of products have been addressed with the engineering of some bacteria to be

dependent on nutrients that may have limited availability, or by including self-destruct mechanisms in organisms

should their population become too great. Biosecurity and biosafety regulations need to be continually reviewed,

to avoid unintentional misuse of the technology, in particular to prevent the production of harmful organisms

for bioterrorism.

Intellectual property is likely to be complicated as applications of synthetic biology involve several disciplines

and likely will embody multiple patented inventions. Clear structures for managing intellectual property rights

are important to promote continued innovation.

The Rural Industries Research and Development Corporation (RIRDC) invests in research and development to support rural industries to be productive, profitable and sustainable. RIRDC’s National Rural Issues program delivers independent, trusted and timely research to inform industry and government leaders who influence the operating environment of Australia’s rural industries. This research informs policy development and implementation, identifies future opportunities and risks, and covers multiple industries and locations.

Published by the Rural Industries Research & Development Corporation, C/- Charles Sturt University, Locked Bag 588, Wagga Wagga NSW 2678, August 2016

© Rural Industries Research & Development Corporation, 2016. This publication is copyright. No part may be reproduced by any process except in accordance with the provisions of the Copyright Act 1968.

ISBN 978-1-74254-881-4

RIRDC publication no. 16/035

Please note This fact sheet has been developed through research of publicly available information and interviews with industry participants and experts. The content is for general information purposes only and should not be relied upon for investment decisions. Case studies were prepared from interviews conducted in 2016 and reflect the use of the technology at that time.

The components of the food and fibre

supply chain that may be transformed by synthetic biology.

Processing

Farm operations

Natural resources

Consumers

Labour and skills

Logisitics

Inputs

More information � Synthetic Biology: Putting the engineering back

into genetic engineering

www.youtube.com/watch?v=rD5uNAMbDaQ

� Synthetic Biology Project

www.synbioproject.org

� Enabling technology futures: a survey of the

Australian technology landscape.

www.industry.gov.au/industry/IndustrySectors/

nanotechnology/Publications/Documents/

EnablingTechnologyFutures.pdf

� Synthetic Biology Social and Ethical Challenges

stopogm.net/sites/stopogm.net/files/webfm/

plataforma/syntheticbiologychallenges.320.pdf

Series detailsThis fact sheet is one of a series on new and emerging

transformative technologies in Australian agriculture.

You may also be interested in reading about:

� Gene editing

� Nanomaterials

EnquiriesE: [email protected]

W: www.rirdc.gov.au

Farm operations