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Case Studies Exploring the Impact of Synthetic Biology on Natural Synthetic Biology, Biodiversity & Farmers www.etcgroup.org Case studies exploring the impact of synthetic biology on natural products, livelihoods and sustainable use of biodiversity Synthetic Biology, Biodiversity and Farmers ETC Group ...works to address the socioeconomic and ecological issues surrounding new technologies that could have an impact on the world’s poorest and most vulnerable people. We investigate ecological erosion (including the erosion of cultures and human rights); the development of new technologies (especially agricultural but also other technologies that work with genomics and matter); and we monitor global Synthetic Biology, Biodiversity and Farmers governance issues including corporate concentration ...is ETC Communiqué #116 and trade in technologies. We operate at the global Published April 2016 political level. We work closely with partner civil Editing by Holly Dressel society organizations (CSOs) and social movements, Additional case study research by Marie-Pier Munger, especially in Africa, Asia and Latin America. Kathy Jo Wetter, Hope Shand and Dru Ojay www.etcgroup.org Design and Illustration by Stig ETC is grateful to The Swift Foundation for financial support in the preparation and revision of these case studies. 2 Synthetic Biology, Biodiversity and Farmers Contents 13 Case studies Introduction 3 Agarwood 12 What is Synthetic Biology? 4 Ambergris / Clary sage 16 4 The Switch to Ingredient Markets Artemisinin 19 Metabolic Pathways to Everything 4 Ginseng 22 Industry’s Synbio Advantage 6 Patchouli 25 Answering the Hard Questions on Syn Bio 6 Rose Oil 28 Disrupting Who? 7 Saffron 32 The Global Flavor & Fragrance Industry 9 Sandalwood 36 Endnotes for Introduction 10 Shea, Cocoa butter & CBEs 42 Squalane (Olives) 49 Stevia 54 Vanilla 59 Vetiver 64 Introduction At the sharpest end of this disruption are the farmers, growers, pickers and harvesters, particularly in the tropics, who provide the natural products that A fundamental shift is underway in how food, make up the ingredients in our foods, cosmetics, flavor, cosmetic and fragrance ingredients are being soaps, textiles and more. Consumers and workers produced for global markets. The new game in town will also be affected. is biosynthesis – the artificial production of key In this report ETC Group presents a series of case compounds by synthetically engineered organisms. studies outlining ways that specific products are While consumers, farmers and the natural world being bio-synthetically created, and how current have already had to grapple with the impacts of the livelihoods from traditional agricultural production last synthetic revolution (synthetic chemistry), may be adversely affected as these synthetic biology- which has created many toxic, harmful or noxious based substitutes for high value commodities enter substances and polluted systems, this next synthetic the market. Several of these synthetic substitutes are revolution (synthetic biology) is set to have equally already in commercial use; some taking major disruptive effects. These impacts range from safety market share already; and many more are rapidly and environmental concerns to very profound social headed towards commercialization, potentially and economic upturning of livelihoods and displacing the work of already marginalized peoples landscapes. in their wake. ETC Group www.etcgroup.org 3 What is Synthetic Biology? With synthetic biology, the goal is to produce high-value Synthetic biology, dubbed “genetic engineering flavor/fragrances by using engineered microbes on steroids,” broadly refers to the use of instead of relying on costly botanical computer-assisted, biological imports or conventional chemical “The overall engineering to design and construct synthesis. The biosynthetic absolutely novel synthetic aim of synthetic biology manufacturing platform involves biological segments, devices and is to simplify biological the engineering of genetic systems that do not and never engineering by applying pathways in microorganisms, have existed in nature; it also engineering principles and which alters them so they produce molecular compounds refers to the redesign of existing designs—which emanate from biological organisms using these that previously have been electronic and computer extracted from plants. Scientists techniques. Synthetic biology engineering—to attempts to bring a predictive and software engineers are tweaking biology.” 1 engineering approach to biological the DNA of existing microorganisms as genetic engineering using genetic “parts” that well as designing new ones from scratch. are thought to be well characterized and whose In the words of one industry analyst: “There is behavior can in theory be rationally predicted. potential for biosynthetic routes to completely replace any natural sources.” – Kalib Kersh, Lux Research, The Switch to Ingredient Markets quoted in Chemical & Engineering News.3 Over the past decade, before world oil prices plunged, fledgling syn bio start-ups (with the financial backing of Metabolic Pathways to Everything fossil fuel corporations) made grandiose claims about Even though plant product metabolism is extremely using designer microbes to produce plentiful, low-cost complex, with advances in molecular biology and biofuels in giant fermentation tanks. Manufacturing engineering, researchers are attempting to pinpoint the petrochemical substitutes at commercial scales proved precise biochemical instructions in the cells of a living elusive, however. Now with energy markets sputtering, organism that result in the production of bioactive most syn bio companies are giving up on biofuels and molecular compounds. In one well-studied plant, turning to high-cost, low volume flavor and fragrance Arabidopsis thaliana (a.k.a. mouse-ear cress or thale molecules that can be economically produced in smaller cress), at least 20% of the genes are thought to play a role 4 batches.2 in the biosynthesis of secondary metabolites. The Biodiversity – especially exotic plants and animals – complex interaction of genes and enzymes in their has been the source of natural flavors and fragrances for natural context all play a role in the plant’s “metabolic millennia. Plants, animals and microorganisms are pathway” – the means by which it produces a useful prolific generators of bioactive flavor/fragrance chemical compound. compounds, known as secondary metabolites, that, once Using “metabolic pathway engineering,” synthetic extracted, are widely used in food, feed, cosmetics, biologists are turning microbial cells into “living chemicals and pharmaceuticals. chemical factories” that can be induced to manufacture The world’s largest flavor and fragrance corporations substances they could never produce naturally. To d a t e , are eager to partner with synthetic biology companies synthetic biology firms are honing in on the best-known because of increasing production uncertainties caused by metabolic pathways such as terpenoids, polyketides, climate change, as well as the alluring potential of alkaloids – these pathways are the keys to producing tens securing cheaper, uniform and more accessible sources of of thousands of natural product families at the molecular economically desirable natural ingredients. level. 4 Synthetic Biology, Biodiversity and Farmers “There is potential for biosynthetic routes to completely replace any natural sources.” Kalib Kersh, Lux Research, quoted in Chemical & Engineering News.3 To scale up the production of a desired compound, the In the words of one venture capitalist, Bryan Johnson, novel biosynthetic pathway (constructed with synthetic founder of the OS Fund, the ultimate goal of syn bio is DNA) is inserted into a microbial host (yeast, bacteria, to control biology and make it predictable: “We aren’t fungi or algae strains, for example) that feed on plant there yet with biology... I can’t just sit down and program sugars in giant (e.g., 200,000-litre) fermentation tanks. biological code to create a particular outcome on a more In the words of synthetic biologist Jay Keasling: “We complex scale. What’s standing between us making good ought to be able to make any compound produced by a use of that is our ability to make it predictable.”8 5 plant inside a microbe.” Despite the techno-rhetoric, the design and control of The engineering of microbes for industrial purposes is synthetic organisms is far from routine, simple or nothing new, but synthetic biology start-ups are inexpensive. Biosynthetic pathway engineering is highly accelerating the process with computer engineering complex. Just two examples: principles and highly automated, robotic systems. In a • Researchers at Amyris, Inc. (California) successfully mostly random process, software-directed robotic engineered the metabolic pathway of yeast to produce systems design, build, test and analyze DNA sequences artemisinic acid, a precursor of artemisinin, an effective and active compounds to identify promising candidates drug to treat malaria, which is typically sourced from and optimize biomolecular pathways in microbes. the Chinese wormwood plant.9 The biological Despite the staggering complexity of biological systems, engineering involved at least 12 new synthetic genetic synthetic biologists compare themselves to industrial parts10 (and more than $53 million in research product designers: “This design strategy can be likened grants11). to building millions of variants of a chemical factory, • Evolva (Switzerland) commercialized a proprietary selecting or screening
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