Review of BIO’s Pacific Rim Summit: December 10-11

Bio Pac RimDecember 10th at the Biotechnology Industry Organization Pacific Rim Summit on Industrial Biotechnology and Bioenergy (BIO PacRim) Conference began with the morning Breakfast Plenary Session entitled Pac Rim CEO Spotlight which was moderated by Paul Zorner, a former Diversa employee and current Operating Partner of Pegasus Capital Advisors.? The panel consisted of Joel Cherry (JC) of Amyris, Lee Edwards (LE) of Virent, Kirk Haney (KH) of SG Biofuels and James Levine (JL) of Verenium (now a division of BASF).? The session began with each panelist providing a brief synopsis of some recent progress at their company and a glimpse into their strategic leadership down the road.? JC commented that their platform or strain engineering technology to generate biocatalyst proficient in the biosynthesis of a particular molecule is the ?tip of the iceberg? in Amyris? effort to deliver No Compromise? replacement molecules starting with farnesene as a drop-in transportation fuel.? KH talked about their genomic engineering platform for the rapid domestication of new crops, such as jatropha and its seed oil, involving laboratory instrumentation that didn?t exist three years ago.

Zorner facilitated the panel discussion by posing his own questions as well as some selected from audience submissions.? When asked about effective strategies for diversification, LE spoke analogously by saying that if you hook yourself up to one horse, then you end up going in the direction desired by that one horse.? JL referred to the mantra, products do not sell themselves, as far as describing his method of navigating thru the challenges of diversification especially with respect to windows of opportunity and commercialization.? KH added that his approach is built on three strengths, those being proven and protected technology, solid business development, and collaboration.

As for being questioned about their 20/20 hindsight developed over the last three years and what they would do differently, each panelist spoke about too much, too fast whether it was spending too much on too many technology trials with too many partners versus cultivating fewer and deeper working relationships, succumbing to pressure to go too fast too soon, and picking a winner too early.? A strategy from lessons learned by LE from 20/20 hindsight is identifying what he described as a healthy tension between the working parts as an indicator to stop tweaking [a technology or process] and lock-it down.

The Special Topics-Workshops section of the conference began after the Breakfast Plenary Session.? One of the four workshops was titled Blue + White = Green, which delved into exploring and mining the vast ocean worlds (Blue Biotechnology), both deep and arctic regions, to understand how survival occurs in nature that could possibly guide strategy applied in industrial biotechnology (White Biotechnology) to arrive at environmentally friendly and sustainable processes (Green Biotechnology).? The session was moderated by Kenneth Barrett, VP of Business Development at Verenium.

Jody Deming of the School of Oceanography at the University of Washington presented her research on extracellular polysaccharide substance (EPS).? The ice columns or ice cores bored from the arctic ice are essentially living laboratories that trace the evolution of survival as a function of temperature and brine concentration. ?EPS formation is a stress response, for example to extreme cold or salt concentration, and its variability is key to survival.? Some roles of EPS include influence on formation of ice crystals, anchoring of microalgae within ice columns and stabilization of cell functional and structural components.

Doug Bartlett, a marine microbiologist at the Scripps Institution of Oceanography, discussed the identification and analysis of microbiological organisms found in very deep regions of the ocean which are subject in part to extremely high hydrostatic pressure.? Bartlett was the Chief Scientist of the DeepSea Challenge Expedition of a submersible manned by Hollywood director James Cameron which dived to the deepest depth of the ocean, which is the Mariana Trench some seven miles below the surface.? The high hydrostatic pressure, zero level of sunshine and unique nutrient supply provide for diverse and distinct microbial populations.? An application in biofuels is the varying poly-unsaturated fatty acid profiles found in certain organisms as a function of sea depth plus some findings that are being applied to the development and commercialization of hydrogen production.? Bartlett also revealed the possibility for discovery of marine natural products that may provide a window for the health and biomedical field, for example the identification of the organic osmolyte scyllo inositol in a deep sea microbe.? Bartlett commented that scyllo inositol was already in clinical trials for treatment of Alzheimer?s disease which have been fast-tracked by the FDA.? Scyllo inositol is one of eight stereoisomers of the naturally occurring plant cyclic sugar alcohol inositol and its interaction with amyloid peptide may lead to the attenuation of its neurotoxic effects.

Two other presentations included that by David Weiner, VP of R&D at Verenium, and Neil Parry, Director of R&D at Unilever.? Weiner discussed the enzyme technology platform at Verenium resulting from directed evolution and screening of 2000 environmental DNA libraries extracted from one million organisms mined from all over the globe including the ocean.? Perhaps a new source of diversity for Verenium?s libraries will come from whale falls, remains of whale carcasses that was presented as an image in one of Weiner?s slides, discovered at the bottom of the Antarctic giving rise to colonization of unknown deep sea species thriving on the nutrients available from the whale remains.

One example of a commercial product offered by Verenium noted by Weiner includes Pyrolase which is a cellulase isolated from a deep sea geothermal vent with a major application being biocatalytic viscosity reduction, or guar gum breaking, involved in deep well oil recovery and hydraulic fracturing.? Weiner also offered progress on another soon-to-be commercialized lipase enzyme product engineered for use as a molecular tweezers in the selective hydrolysis of triacylglycerol-based oils during their refinement resulting in release of a certain fatty acid to create healthier edible oils.? Parry presented Unilever?s application of ice structuring proteins isolated from Icelandic flounder in the production of improved quality ice cream.? Unilever is also involved in anti-biofilm technology which acts by interrupting the mechanism of quorum sensing in a non-biocidal fashion which has advantages in that it will not result in reduced effectiveness upon development of bacterial resistance.

One afternoon breakout session was Renewable Chemical Platforms: Processes Leading to Commercialization.? It featured Atul Thakrar from Segetis who spoke about levulinic acid and its advantage of being a C5 molecule with oxygen molecules built-in by nature.? Thakrar emphasized the importance of having a capital-lite process and an investor appetite with a long-term horizon as key success factors to commercialization.? Other important factors spelled out by Thakrar that need to be identified as part of successful commercialization included a need for change, an interest for change, and importance to the end-user.? Marcel Lubben of DSM listed five must-haves for commercialization which were 1) select a winning feedstock, 2) being truly technology agnostic, 3) funding matched with business model, 4) partnership/alliances forged with key players/technology, and 5) derisk derisk derisk.? All the panelists agreed that the renewable chemicals business needs to rapidly get to the stage of commercialization when there is no longer talk about or celebration of plant start-ups and instead move-on to press releases about improved production or reduced cost like they do in the petroleum world, which stemmed from a closing comment made by Susan Hager, SVP Corporate Communications and Government Affairs of Myriant, who had given a presentation on Myriant?s build-own-operate business model for production of C3 ? C6 target molecules including their flagship commercial product bio-succinic acid.

Wednesday December 11th was the last day of the conference and one Breakout Session was titled Innovation in Renewable Chemical Platforms (IRCP) which was moderated by Peter Keeling, Innovation Director of the Center for Biorenewable Chemicals (CBiRC) at Iowa State University.? Karl Sanford of DuPont spoke about the greening of DuPont, a task which starts by determining how a petrochemical-derived product can be made from a renewable feedstock.? Sanford stressed that delivering sustainable solutions in the greening process hinges on science and collaboration as evident from projects involving BP, Danisco and Genencor.? Key imperatives for biofuels growth presented by Sanford included use of nonfood feedstock such as their Corn Stover Harvest Collection Program initiated as part of their Cellulosic Ethanol Facility in Nevada, Iowa, drop-in and higher energy fuels such as biobutanol from their ButaMax joint venture with BP, and Early Adopters Group to rapidly launch commercial production which involves the strategy of retro-fitting existing infrastructure.

Another presenter Wednesday morning was Jamie Bacher, Founder and CEO of Pareto Biotechnologies.? The technology platform at Pareto is based on a decade or so of research by Joseph Noel of the Salk Institute. ?Noel is also a founder of Pareto, and earlier founded Allylix.? Pareto?s core technology out of the Noel lab is based on the chemical reaction catalyzed by the enzyme polyketide synthase (PKS), from which the near term goal will be production of designer molecules for the cosmetics, flavors and fragrances industry.? PKS catalyzes three reactions at one active site which essentially provides three points of entry for the design of molecules.? The first point of entry is the PKS substrate which can be an alternative or non-natural substrate and thus may require some engineering of the active site for substrate specificity and or catalytic efficiency.? The second point of entry is the second reaction and its control which is iterative polyketide elongation.? The third point of entry is the third reaction which is cyclization and the control of its regiospecificity which seems programmable by protein engineering to alter active site surface chemistry and or geometrical structure.? A fourth point of entry is to build-in chemical handles of organic reactive functionality to exploit after the PKS reaction which was referred to as post-fermentative chemistry.? Pareto has just received a $350,000 grant from the San Francisco-based Thiel Foundation?s Breakout Labs.

Another speaker in the IRCP breakout session was Jeff Fornero of Glucan Biorenewables.? GlucanBio was spun out from CBiRC in 2012 and also involves technology developed by Prof James Dumesic at the University of Wisconsin-Madison which is a partner institution of CBiRC.? GlucanBio has licensed technology that represents a game-changing process for the production of furfural, an estimated $3 billion global market.? The major game-changing component of the process is the change from an aqueous-based reactor system to an organic solvent-based system by application of gamma-valerolactone (GVL).? The process has passed the test using pure glucose and xylose with the next phase of proof-of-concept being to use a lignocellulosic feedstock such as corn stover as the source of C5 and C6 sugar for conversion by dehydration.? The process consists of a thermal reactor containing GVL, mineral acid and biomass.? Furfural is produced from the hemicellulose fraction while levulinic acid (LA) is produced from the cellulose fraction.? Furfural can be distilled from the final product mix or it can be catalytically converted in the mixed product stream to LA which in turn can be converted to GVL.? A portion of the GVL is recycled back to the reactor and the rest can be used as a chemical intermediate to produce gasoline, diesel, jet fuel and chemicals.? The GVL system offers several advantages including 1) simultaneous conversion of cellulose and hemicellulose, 2) elimination of pre-treatment and extraction/separation steps thus reducing capital expenditure, 3) effective solubilization of the biomass including the lignin and degradation components thus eliminating problematic reactor issues from solids accumulation, 4) optimization of furfural yield by reduction of degradation rates, 5) increased rate of cellulose conversion to LA, and 6) miscibility with water which permits use of wet biomass.? At the end of the presentation, Fornero disclosed that GlucanBio has entered into a joint development agreement with Chevron-Phillips which is one of CBiRC?s Industry Members.


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