In Washington, the National Research Council arm of the National Academies has released its report, “Industrialization of Biology: A Roadmap to Accelerate the Advanced Manufacturing of Chemicals,” including a series of goals, recommendations and conclusions to expand the use of industrial biotechnology to transform the sustainability and cost of chemical production.

In today’s Digest, we’ll feature a series of excerpts from the report,which can be downloaded free in its 144-page entirety here, and is a must-read.

The Potential

The Council writes: “In its 2012 National Bioeconomy Blueprint, the Obama Administration defined the bioeconomy simply as “one based on the use of research and innovation in the biological sciences to create economic activity and public benefit”. It went on to observe that “[t]he U.S. bioeconomy is all around us,” with new bio-based chemicals, improved public health through improved drugs and diagnostics, and biofuels that reduce our dependency on oil.”

The market is already significant, they say: “Bio-based product markets are already significant in the United States—representing more than 2.2 percent of gross domestic product, or more than $353 billion in economic activity in 2012…Current global bio-based chemical and polymer production is already estimated to be about 50 million tons each year, and bioprocessing techniques (such as fermentation, baking, and tanning) have been used throughout much of human industrial history.

Today, “Agilent Technologies estimates that U.S. business-to-business revenues from industrial biotechnology alone reached at least $125 billion in 2012. Bio-based chemical applications accounted for about $66 billion of that activity with biofuels adding another $30 billion.”

But wait, there’s more: “Despite this impressive recent and projected growth, the manufacturing of chemicals using biological synthesis and engineering could expand even faster…The advanced manufacturing of chemicals through biology can help address global challenges related to energy, climate change, sustainable and more productive agriculture, and environmental sustainability. For example, these processes may help reduce toxic by-products, reduce greenhouse gas emissions, and lower fossil fuel consumption in chemical production. Lowered costs, increases in production speed, flexibility of manufacturing plants, and increased production capacity are among the many potential benefits.”

The Science Is Advancing


The Council points to advances in genetics as a driver of “now”: “The genetics underlying the natural world are being illuminated by DNA sequencing, the cost of which is declining rapidly. The first human genome (3.2 billion base pairs [bp]) was sequenced in 2001 at a cost of $2.7 billion. Nine years later 1,000 human genomes (3.2 trillion bp) were sequenced and in 2014 the company Illumina released the HiSeq X, promising a $1000 human genome.”

Industry Is Ready

The Council notes that because “the applications of synthetic biology in human health and agriculture have advanced more quickly than for the manufacturing of chemicals…groundwork has been laid for the manipulation of genes and proteins to beneficial purposes and for the scaling of bioprocesses to large volumes.”

It’s a complex effort, they acknowledge, writing that “in contrast to health and agriculture applications, synthesis of a chemical product requires the coordination of the expressions of many genes. Biologically produced chemicals are the result of a series of enzyme-catalyzed reactions, with each enzyme encoded by at least one gene. In total, the expression of as many as dozens of genes must be regulated to affect a chemical synthesis. Based on early successes…the growth of this field will enable the use of biology to produce high-valued chemical products that cannot be produced at high purity and high yield through traditional chemical synthesis.”

Representing up to 65 percent of costs, the challenge begins with feedstock and supply chain

Although the Council forcused on a wide variety of factors and opportunities from genes all the way to product, the first challenge is sustainable, affordable, reliable, available feedstocks. As the Council observed, “Scientific and engineering challenges remain, particularly in the areas of feedstocks, enabling transformations, and the development of an integrated design toolchain…In the case of large-volume chemicals, sugar costs can represent the majority of the total product costs. In the extreme case of biofuels, sugar costs represent as much as 65 percent of the total product costs.”

Grain-Derived Sugars and the need for alternatives

The Council frames the challenge thus: “Although [starch derived from grain] has served the industry well, there are limitations to the supply of grain and concerns about competition with the food and feed uses for grain. Ultimately, the supply of high quality, arable land is finite, in the United States and globally. Yields per unit area will continue to increase, through improvements in agronomic practices, breeding of higher-yielding cultivars, and the application of agricultural biotechnology. Yields can be expected to improve by 1 to 2 percent per year in the developed world, and by somewhat higher rates in the developing world, where the yield baseline is lower. The projected rates of yield improvement will ensure an adequate supply of our food and feed needs. Alternative sources of carbon are needed to realize our full ambitions for the biological production of chemicals.”

Lignocellulosic Biomass

The Council writes: “A number of challenges must be overcome if cellulose-based sugars are to become fully substitutable for starch-derived sugars, and with a cost advantage. Today’s agricultural economy has well-functioning markets for grain trading, and a well-established infrastructure for the production, transportation, and storage of the commodities. None of this exists for fermentable sugars derived from cellulosic feedstocks. The cost of the cellulosic feedstock must be kept low—much less than $100/ton—in order for it to be a viable alternative to grain.”

It will start with ag residues, they conclude:  “A current generation of cellulosic ethanol plants will rely on corn stover (stalks, leaves, and cobs); other sources of cellulose are available from agriculture; wheat straw, rice straw, and sugarcane bagasse are all examples.”

But rapidly focus will shift to lignin: “Lignin constitutes about 20 percent of corn stover mass. It is currently recovered and valued as a fuel. As the use of cellulosic feedstocks expands, strategies are needed to derive additional value from lignin so that it can be used as a co-product rather than a waste stream from fermentation”

Attention may shift to forest resources, especially if lignin is unlocked and faster-growing trees emerge: “The forestry industry also produces residues that are a potential source of sugars. The “hard” cellulose that constitutes wood is characterized by its higher hemicellulose and lignin contents (lignin approaching 40 percent by mass for some wood).  Forestry residues exist in large quantities, and they are often readily available at the saw mill for further processing…Fast-growing trees also hold potential as sources of fermentable sugars, in much the same way that they provide feedstocks for pulping processes. This source faces the twin challenges of the long time needed to establish the crop, and the challenge associated with the high lignin content of “hard” cellulose sources.”

Another area of opportunity is dedicated energy crops and perennial grasses. The Council writes that although “cropping patterns change slowly,” and “It is unlikely that land used for today’s crops will be converted to production of an energy crop,” they foresee that “annual crops such as sorghum have great potential to be a future source of cellulosic feedstock. Sorghum is well adapted to the more arid conditions of the U.S. western Great Plains.  Perennial grasses…have the potential to augment biomass supply without competing for today’s agricultural land. The principal disadvantage of perennial grasses is the 2 to 3 years needed to establish the crop. This constitutes a significant economic penalty at startup.”

C1 Feedstocks

The Council notes the opportunity with methane and other C1 feedstocks such as carbon monoxide. They write: “Cheap, abundant natural gas (whose composition is essentially methane with trace amounts of other hydrocarbons) from unconventional sources is revolutionizing the U.S. energy and feedstocks landscape. Natural gas is replacing the products of naphtha crackers as the preferred feedstock for many chemical products. In addition to unconventional gas, there are also biological sources of methane from landfill gas or the biological digestion of biomass. Methane and its derivatives such as methanol, syngas, or formate all have potential as carbon sources for fermentation.”

But they see challenges with the C1s: “Considerable technical challenges exist. Two-phase gas-liquid fermentation reactors are complex and costly. Both methane and hydrogen are sparingly soluble in aqueous media. Gas-liquid mass transfer is a significant impediment to high volumetric productivity in the fermenter. However, at least three demonstration-scale syngas-to-ethanol facilities are operating today. Additional process engineering and host organism research are needed to expand the economic viability of C1 feedstocks for the biological production of chemicals.”

Key Conclusions

The Council had three conclusions and three roadmap goals for feedstocks.

Conclusion: Improvements in availability of economically feasible and environmentally sustainable feedstocks are necessary to accelerate the production of fuels and high-volume chemicals via bioprocessing.

Conclusion: Improvements in the availability, reliability, and sustainability of biofeedstocks including: cellulosic feedstocks, lignin, methane, methane derivatives, carbon dioxide, and formate as feedstocks and noncarbon feedstocks (e.g., metals, silicon), would increase the range of economically viable products…and lower barriers to entry into the biological production of chemicals.

Conclusion: Improving the basic understanding of C1-based fermentation, including both host organism and fermentation processes, is enabling in light of the increased availability of natural gas in the United States.


Roadmap Goals

• Within 4 years, for biological processing, achieve widespread use of novel sources of carbon, such as fermentable sugars derived from soft cellulose at a full cost less than $0.50 per kilogram of substrate.

• Within 7 years, for biological processing, achieve widespread use of novel sources of carbon, such as fermentable sugars derived from soft and hard cellulose at a full cost less than $0.40 per kilogram.

• Within 10 years, for biological processing, achieve widespread use of diverse sources of carbon, such as lignin, syngas, methane, methanol, formate, and CO2, in addition to fermentable sugars derived from soft and hard cellulose at a full cost less than $0.30 per kilogram.

The Digest’s Take

The Council’s work is detailed and applaudable, as far as it goes. But we found the Council’s avoidance of any discussion of advanced oilseeds; algae; urban residues such as fats, oils and greases and muncipal solid waste to be a missed opportunity.

There is significant carbon available from these resources, in many cases derived from abundant materials such as CO2, sunlight and saline water; or from ultra low-cost sources such as waste collection. Already, these sources are being used at scale to make chemicals and fuels — for example, Enerkem’s commercial-scale facility in Alberta, Solazyme’s commefcial-scale production in Clinton, Iowa; and the signficant production of both biodiesel and renewable diesel by companies such as Renewable Energy Group (which recently acquired the advanced synthetic biology start-up LS9 to pursue work in areas such as chemical production).