Bio-based chemicals broaden their scope

C&I Issue 21, 2011

The response to higher energy prices and greenhouse gas emissions has been the rapid development of alternative fuels like bioethanol and biodiesel as a substitute for fossil based transportation fuels. While first generation biofuels are now well established, and second generation cellulosic fuels are well into development, as Zhiyou Wen, from Iowa State University, US, points out algal biofuels are at least a decade away from full commercialisation.

Speaking at the 2011 annual meeting of the US Society of Industrial Microbiology, he said that to maintain the development of such biofuels, most importantly through the continuation of funding, it is necessary to look at developing high value co- or by-products to generate the necessary revenues to provide that funding. ‘Higher value products can pave the way for fuels,’ he said.

The point was also made succinctly by John Hamer, from venture capital firm Burrill, who said: ‘If you can’t sell biofuel at $12/gal then make a cosmetics ingredient that will sell at $12/gal.’

Zhiyou Wen’s focus has therefore been to look at the algal production of omega-3 fatty acids to meet the needs of a supplement market that is currently supplied from fish. This source, however, has its own problems, including the impact of over-fishing, potential heavy metal contamination, as well as problems of odour and taste in fish-based products. But fish do not produce omega-3 fatty acids like humans, obtaining the acids from microalgae, he noted, so why not use microalgae to produce the acids directly?

His research has looked at two key omega-3 fatty acids: DHA, produced using the microalga Schizochytirum limacinum; and EPA, produced using the algal-like fungus Pythium irregular, with glycerol derived from biodiesel production as the feedstock. He pointed out that the biomass resulting from the production could be directly used as an animal feed containing a high level of DHA/EPA. Freeze dried algal biomass had been fed to chickens and the fatty acids identified in the chickens’ eggs. EPA production was still at an early stage, he added, pointing out that it has not reached commercial scale, although pilot testing has been conducted using contract manufacturing.

Competition for petrochemicals

The associated concept of the biorefinery has led to the development of bio-based chemicals as a replacement for petrochemicals. Back in 2004, the US Department of Energy (DoE) identified 12 so-called top platform chemicals that it had targeted for bio-based development, including 1,4-succinic, fumaric and malic acids; 2,5-furan carboxylic acid; 3-hydroxy propionic acid; aspartic, glucaric, glutamic, itaconic and levulinic acids; 3-hydroxybutyrolatone; glycerol; sorbitol and xylitol/arabinitrol.

Biobased succinic acid is a major development target although the global market is relatively small, 25,000-35,000t/year for the petroleum derived acid. Succinic acid is, however, used directly in a variety of industrial applications in the pharmaceutical, food and automotive sectors and as an intermediate for the production of several high performance polymers.

Mickel Jansen, from the Biotechnology Center of Dutch materials science company Royal DSM, described the joint development of their commercialised biorenewable succinic acid, Biosuccinium, through Reverdia, DSM’s 50:50  joint venture with French starch specialist Roquette.

Jansen pointed out that for the future success of the bio-based acid it would be important to realise the lowest possible cost price and for that reason a fermentation process at low pH, using Saccharomyces cerevisiae and corn starch as the feedstock, is used to directly produce the acid. The maintenance of pH3 conditions minimises salt production in the recovery process thereby reducing the investment costs and also lowering the carbon footprint and utility costs due lower steam requirements. Using metabolic engineering, Jansen said it has been possible to produce higher titers and yields of the acid, around 100g/L with minimised production of the by products including ethanol and glycerol.

Currently, Reverdia has successfully scaled up succinic acid production to around 100m3, but a 10,000t/year plant is scheduled to come on stream in Cassano, Italy in 2012, while a second commercial plant is already in the planning stage, Jansen added.

Portuguese researchers at the Universidade Nova de Lisboa have been looking at the use of Actinobacillus succinogenes and glycerol, the abundant by-product of biodiesel production, to produce succinic acid. Although they admit that glycerol utilisation is not yet efficient in terms of volumetric productivity or specific growth rates, there is limited formation of by-products during the fermentation, which could simplify downstream purification.

Current work is focused on the development of continuous high cell density fermentation to increase succinic acid production.

Succinates based on soybean carbohydrates are under development at Rice University, Houston, Texas, US. The researchers are using engineered strains of E.coli for both aerobic and anaerobic fermentations in work supported by the United Soybean Board.

Succinic acid is used in the production of 1,4-butanediol (BDO), however, Californian developer of sustainable chemicals, Genomatica, has used metabolic engineering to develop E.coli strains for BDO production using glucose and sucrose as the feedstocks, without going via succinic acid.

Genomatica’s Stephen Van Dien told delegates that titers of 100g/L or more, approaching the maximum possible yield of BDO, have already been achieved with reduced by-products at levels of 13,000L at a demonstration-scale plant since June 2011.

Genomatica expects the first commercial-scale BDO plant, with a capacity of approximately 18,000tpa of BDO, will be located in Europe. It will be owned and operated by one of the company’s industry partners, Novamont, with production scheduled to begin by the end of 2012. Genomatica is also planning larger commercial-scale BDO plants owned and operated together with other industry partners in the US, Europe and Asia to begin production in 2014.

Another of the top 12 platform chemicals, 3-hydroxypropionic acid (3-HP), is a precursor for acrylic acid. Jae Yong Kim, responsible for what he described as ‘frontier research’ at  (SAIT), a subsidiary of Korea’s Samsung Electronics, looked at the development of a bio-based route to this important precursor.

While he declined to reveal any specific details, he did say that SAIT has identified a number of metabolic pathways that can produce 3-HP and one particular microbial strain has been developed offering high xylose consumption giving high efficiencies in terms of biomass usage.

Current work at the US Department of Agriculture is focused on the production of fatty acids, including erucic, ricinoleic and lauric acids as well as conjugated fatty acids. The goal, as described by Jay Shockey, from the USDA’s Agricultural Research Service in New Orleans, is to engineer conventional oil seed crops to act as biorefineries to produce these acids. Initial work has focused on eleostearic acid, which is conventionally obtained from the Tung tree (Vernicia fordii), an increasingly restricted resource.

Although baker’s yeast, Saccharomyces cerevisiae, is often used as a bioreactor to produce such products, Shockey noted that it has not been used for the conversion of common triacylglycerols because the microbe is unable to take up such lipid substrates from the growth medium. The conversion has been achieved by incorporating a lipase gene from the hemiascomycetous yeast, Yarrowia lipolytica, which can produce methane form lipids and citric acid from n-alkanes, vegetable oils and glucose under anaerobic conditions.

Shockley said the work has shown that a self-regulating positive feedback control loop was created, which allows the microbe to up-regulate lipase production only when lipids are present in the growth medium.

Such metabolic engineering was described by Sang Yup Lee, from the department of chemical and biomolecular engineering at the Korea Advanced Institute of Science and Technology (KAIST) as the purposeful modification of a metabolic network to achieve enhanced production.

In his Amgen keynote presentation, however, he also pointed out that the key problem in such engineering is the complexity of the network itself. It is essential to identify the exact route in order to overcome competitive objectives, and here, he believes, in silico modelling and simulation have a major role to play.

But he also believes that metabolic engineering will move out of just the production of basic chemicals into entirely new areas, such as the use of microbial fermentation to produce quantum dots for quantum dot light emitting diodes (QLEDs), the next generation beyond organic LEDs (OLEDS), for the manufacture of very bright display screens as well as solid-state lighting systems.

Renewable chemical market set to grow

The global renewable chemicals market is forecast to grow to $76.8bn by 2017, according to recent estimates by US market research firm, Global Industry Analysts (GIA.

In its report Renewable Chemicals: A global strategic business report, GIA says the world market for renewable chemicals rebounded in 2010 after a temporary slide in growth in 2009, and is expected to see double-digit growth over the next few years.

GAI believes the industry ‘has admirably withstood’ the slowdown in venture capital and other funding issues, patent issues, declines in the purchasing of what are seen as expensive bio-based chemicals and deferred investments in their production.

However, the report also states that government support and intervention is expected to increase through incentives and subsidies, particularly for start-up companies seeking to achieve the first level of economies of scale and cost competitiveness, to meet growing demand to replace petroleum-based chemicals.

The industry’s development of bio-based chemicals that facilitate easy substitution with lower transition costs is expected to fuel the market in the short term while future growth is forecast to be based on next-generation novel chemicals.

Although the major share of the market is accounted for by the US and Europe, developing countries in Asia-Pacific, Latin America and the Middle East are expected to take ‘centre stage’ in the future as they move from fossil-based feedstocks.

While the GIA report highlights transportation applications as the largest end-use market in terms of revenue, the food industry is expected to playing an increasing role as it tries to convert its advantage in terms of wider upstream access to the food supply chain, including renewable feedstocks, into an opportunity to manufacture basic chemicals.

Food safety applications are forecast to show the fastest growth of 13.4% CAGR in the period to 2017.

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