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50 Hot Bio-Based Companies, 50 Quick Takes

Renewables are coming to replace Petroleum, predicted by self-proclaimed tech prognosticators everywhere.

On the other end – inflated and unrealistic valuations, a shaky stock market, a weak China, and as the oil prices fluctuate, they will take many smaller and un-mythical bio-based startups down. Why? Because you cannot have a successful bio-based company without a subsidy or an incentive from the government with the era of $44 crude oil! Is the usual reply from the un-familiar!

What is real is, the global population has more than doubled in the past 50 years. As of March 2016, the world population was estimated at 7.4 billion, an all-time record high. The United Nations estimates it will further increase to 11.2 billion in the year 2100. Subsequently, with this increase – has the demand for, and consumption of, energy increased as lifestyle requirements have gone up.

Over this period of rapid growth, the proportion of that consumed energy attributed to fossil fuel has remained fairly steady, falling marginally about 10-12%. A portion of that slight drop is due to a fall in global coal consumption. The first oil price shocks in the 1970s were the trigger for the start of intensive R&D associated with what are today’s renewables: solar, wind, hydro power, together with the range of cultivated biofuels from grasses to algae to municipal waste.

Whilst at a slower pace, renewable (bio-, solar, hydro, wind) fuels provide a reasonable chunk of the energy we use today, and that is in spite of the increasing rhetoric from the fossil industry.

In the conceptual design of the future – towards a sustainable society often times there is a high degree of disengagement with what matters most within the industry and more importantly lack societal needs. Finding an alternative for a 100+-year old petroleum industry is not just trivial but a herculean undertaking. The three obvious pathways to the creation of a sustainable future are via an integrated approach:

  1. Carbon capture and storage – to mitigate emissions from existing infrastructure, such as the ubiquitous iron & steel, cement and chemical industries, along with the aviation, automotive and marine industry etc. to minimize impacts of continued global warming,
  2. Utilize solar, wind and hydro towards CO2 mitigation and electricity generation to address local transportation requirements, and
  3. Focus on a bio-based industry for novel approaches to transportation fuels (heavy trucks, marine, and aviation fuels etc.) but also supplement the chemical requirements (fundamental chemical building blocks, chemical precursors, solvents, lubricants etc.). Exhibit 1.

For those unfamiliar, an approximate estimation of terrestrial biomass growth amounts to 118 billion tons/year, dried. About 14 billion tons of biomass/year are produced in agricultural cycles, and of this nearly 12 billion tons/year are essentially discharged as waste. Obviously, there is enough biomass available at potentially low cost to be used in many dif­ferent ways (upgrading available biomass itself, extracting valuable components, etc.) and many companies have capitalized on various aspects that will be described below on the map; Exhibit 2 and 3.

The ubiquitous oil industry whilst reluctantly, has now realized that renewables are poised to seize the crucial top spot in global energy supply for example: Recent Outlook to 2035 by BP and The Outlook for Energy: A View to 2040 by Exxon Mobil discuss the predicted distribution within the industry.

This hardly leaves time for complacency for those in the renewable sector. In simple words, which goals and projects should be considered top-priority in the coming yearsbesides solar, wind and hydro-based companies in regards to upgrading biomass? The top 50 companies are picked based on a few primary industries i.e., fuels (ethanol, butanol, diesel, renewable jet, marine fuels, CO2 remediation), and chemical based companies. In addition, whilst a detailed study is available for many of these companies in the March edition of Biofuels Digest – a new list is provided for the readers based on feedback from some of the top minds in the industry. In addition, in the wrap-up, I will pick 5 “Hot off the Griddle” contributors to the field that have the potential for capturing the right markets while disrupting existing value chains namely, Green Biologics, Novvi LLC, Licella, Genomatica, and Avantium.

Top 5 Hot off the Griddle

1. Green Biologics

Founded by Dr Edward Green in Oxford, England – Green Biologics Ltd is a renewable fuels/chemicals company focussed on developing and delivering bio-butanol with its technology platform built on Clostridium microbial fermentation. Following its merger in 2012 with Butylfuel™ Inc., and acquiring the assets of Central MN Ethanol Co-op LLC in Little Falls, MN in 2014 Green Biologics is repurposing a 21 million gallon per year ethanol plant to produce normal butanol and acetone, in 2016. With distribution agreements earlier this year, with Texas-based Nexeo Solutions and Acme-Hardesty, a division of Jacob Stern & Sons Inc. and leading supplier of biobased chemicals, Green Biologics is one company which has managed to keep a level head as opposed to the “other” isobutanol company which has failed on multiple occasions giving it a well deserved # 1 spot on the Hot off the Griddle list.

2. Novvi LLC

A joint venture between a very successful global leader Amyris, Inc. and Cosan S.A. Industria e Comercio created to develop, produce, market, and distribute high-performance oils and lubricants from renewable sources. Novvi draws from the strength of both companies, Amyris’ with its synthetic biology platform to produce targeted hydrocarbon molecules from plant sugar and Cosan’s feedstock capabilities, supply and distribution infrastructure. With the most recent, one-third partner American Refining Group, Novvi has definitely made news splash across the industry.

3. Licella

Licella uses the Cat-HTR platform to convert a variety of low-cost, non-edible biomass into stable biocrude oil, which can be refined, in a conventional refinery, into next generation biofuels and biochemicals. Operating over the past eight years Licella has invested AUD$60 million in its technology development, conservatively yet progressively scaling up its Cat-HTR platform to its current Gen-3 version. Licella is a subsidiary of Licella Pty. Limited, which in turn is a subsidiary of Ignite Energy Resources Ltd. (IER), an Australian public unlisted natural resource and energy technology development company. IER has developed a proprietary lignite and biomass-upgrading platform, the Catalytic Hydrothermal Reactor (Cat-HTR). IER operates via three subsidiaries, Ignite Resources Pty. Ltd. (applying Cat-HTR to lignite), Licella Pty. Ltd. (applying Cat-HTR to biomass) and Gippsland Gas Pty. Ltd. (biogenic natural gas resource). With a past collaborative effort with Norske Skog and the latest with Canadian Canfor in 2016 – Licella has one technology that has a huge hidden potential that needs the right investments to flourish.

4. Genomatica

A widely recognized bioengineering technology leader within the bio-chemical industry, Genomatica with its GENO BDOTM process has produced tons of BDO gaining recognition from BASF, Novamont – license and Cargill – production support. The BDO produced continues to extend further into product value chains, with validation from firms including Invista (Lycra® spandex), BASF (PolyTHF®), DSM, Lanxess, Toray, and Far Eastern New Century. With partners including Versalis and Braskem, Genomatica has managed to raise over $125 million in financing from Alloy Ventures, Bright Capital, Cargill, Draper Fisher Jurvetson, Mohr Davidow Ventures, TPG Biotech, VantagePoint Capital Partners, Versalis and Waste Management. Genomatica is one company that keeps delivering – claiming top spot within the chemicals sector.

5. Avantium

A spinout from Royal Dutch Shell in 2000, Avantium was founded with the singular purpose of using advanced catalysis to transform the world of R&D. One of Avantium’s many success stories is the YXY technology to produce PEF: a completely new, high-quality plastic made from plant-based industrial sugars. PEF is 100% recyclable. Early this year, Avantium and BASF announced that they signed a letter of intent to establish a joint venture for the production and marketing of the renewable chemical building block FDCA, as well as marketing of PEF. The joint venture intends to use the YXY process technology developed by Avantium to solidify its world-leading positions in FDCA and PEF, and subsequently license the YXY technology for industrial scale applications. A solid catalysis foundation definitely makes Avantium one of the top future technology providers for the bio-based industry.

Wrap-up

On a closing note – From the maps above, one aspect is clear – the giants within the industry have taken a note of the changes and have slowly expanded their business portfolio’s to renewables – some of them include Coca-Cola, BASF, DuPont, UOP, DONG Energy, Total, Shell, Sasol.

What is certain – Many companies will emerge and perish in due course as the Top 50 change over time!

About the Author

Dr Kapil S. Lokare received his PhD in chemistry from Michigan State University in the United States. In addition to working with bio-based start-ups and creating business insights towards sustainable markets, he has held positions at various globally recognized institutions in the U.S.A., The Netherlands, Australia and Germany. With a strong network of clients based in South/North America, Europe, Southeast Asia and the Oceania, Dr. Lokare has helped launch new bio-based startups and currently resides in Berlin, Germany and oversees the execution and operation of 2 60KLPD ethanol distilleries.

Original article at https://www.linkedin.com/pulse/50-hot-bio-based-companies-quick-takes-kapil-shyam-lokare-phd-1?trk=hp-feed-article-title-publish

CBMNET secures major new industrial biotechnology funding

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The chemicals industry is a vital component of the world economy that is faced by the need to provide innovative and sustainable solutions to provide the resources required for a growing global population. One approach to a more sustainable chemicals industry is the use of microbial cell factories to produce key chemicals from sustainable feedstocks. However, a major barrier to commercial cell-factory-based chemical production is poor product yield. Often this is caused by intoxication of the cells resulting in sub-optimal performance. To address this problem, a £3 million research project (DeTox) to improve the sustainable production of chemicals and biofuels by microbes has been awarded by the Industrial Biotechnology Catalyst fund to a consortium of scientists led by the Sheffield-based Biotechnology and Biological Sciences Research Council (BBSRC) Crossing Biological Membranes Network in Industrial Biotechnology (CBMNet). Professors Jeffrey Green and David Kelly along with Dr Susan Molyneux-Hodgson at the University of Sheffield are working with colleagues at the Universities of York, Nottingham and Cambridge and five companies (Green Biologics, ReBio, Lucite, CPI and Ingenza), to overcome poor product yields by focussing on how the properties of the bacterial cell membrane can be modified to create more robust cell factories.

DeTox is led by the CBMNet co-director Dr Gavin Thomas (University of York) and has benefited from funding from a CBMNet Business Interaction Voucher (BIV) which generated some of the preliminary data underpinning the DeTox project.

“The BIV was very successful from our point of view as we trialled a new method in our lab, which we took right through to the point where we generated novel data. This then went straight into a grant application.”

Dr Gavin Thomas

“The DeTox project is an exciting opportunity to improve the efficiency of cell-based chemical production that emerged from the creative discussions within the CBMNet management board and our industrial partners.”

Professor Jeffrey Green, CBMNet director

Importantly, the project includes a sociological study of collaborative research processes to develop a better understanding of ‘responsible innovation’.

“The approach of integrating sociological study into a technical scientific project is becoming more common, and it’s an approach that has already been shown to add enormous value to research. We’re very much looking forward to working alongside the scientists and engineers in this important research.”

Dr Molyneux-Hodgson, an expert in the social aspects of synthetic biology in the Department of Sociological Studies

“Green Biologics are looking forward to working with the academic community over the next five years. It is with great pleasure that the wider UK academic community has recognised Clostridia as an important industrial microbe and hopefully this will lead to a dynamic and vibrant community.”

Dr Preben Krabben, Head of Innovation at Green Biologics

DeTox is only one of the many achievements of CBMNet. So far it has funded seven Proof-of-Concept grants along with seven Vacation Scholarships (worth over £175,000) and five Business Interaction Vouchers (worth over £50,000). Many of these awards have focused on supporting students and early career researchers to ensure that the biotechnology expertise continues to grow.

“In our first year we have begun to establish an active and engaged community of industrialists and academics. We now need to build on these foundations and promote the importance of an appreciation of the impact that membrane biology can have on industrial biotechnology processes through our project funding streams and meetings.”

Professor Jeffrey Green

CBMNet is always seeking to further strengthen its links with industry so that the expert knowledge of the UK ‘membrane research’ community is translated into improved biotechnological processes. As the network continues to expand, the sum of its collective knowledge will be a significant resource for the UK biotechnology industry to draw upon.

CBMNet research targets efficient renewable chemical production

New research led by a biochemist from the University of Lincoln, UK, will aim to improve the production of an important renewable chemical used in many well-known products.

A major new collaboration has been awarded funding to explore ways of improving the production of n-butanol – a central building block for a number of household and industrial substances. It occurs naturally as a product of the fermentation of sugars and other carbohydrates and is used in a range of domestic and industrial products, predominantly in paints and coatings, but also in diverse areas such as perfumes, food ingredients, natural resins, and as an extractant in the manufacture of antibiotics and vitamins.

Dr Alan Goddard, from the University of Lincoln’s School of Life Sciences, will lead the project with Dr Preben Krabben from Green Biologics Ltd and Professor Ian Graham and Dr Tony Larson from the Centre for Novel Agricultural Products at the University of York.

The collaboration has been awarded a CBMNet (Crossing Biological Membranes Network) grant to explore more efficient and cost-effective ways of generating n-butanol from a variety of feedstocks – the term used to describe plant and algal materials in the production of renewable chemicals. In particular the purification step of n-butanol from the natural fermentation process can be expensive and the research aims to contribute towards improving this process.

Using expertise developed at the University of York, the researchers aim to identify the specific changes that occur during the creation of n-butanol. The changes that are identified will then be incorporated into a new model system, developed at the University of Lincoln, with a view to improving the production process and enhancing the yield.

Dr Goddard, Senior Lecturer in Lincoln’s School of Life Sciences, said: “The funding awarded by CBMNet will provide an exciting opportunity for our lab to continue industrially-relevant collaborations with Green Biologics Limited. The award will benefit the work of Green Biologics Limited as well as provide new opportunities for researchers here at Lincoln. I hope that our partnership will continue to develop based on the findings of this work.”

The project, called ‘Identifying and characterising protective lipid changes under solventogenic stress’, is funded through a CBMNet Proof of Concept Grant of just over £30,000. The CBMNet Proof of Concept Grants support new multi-disciplinary teams as they develop innovative solutions to overcome bottlenecks in the Industrial Biotechnology and Bioenergy (IBBE) sector.

Read the original article here.

CBMNet Business Interaction Vouchers Awarded

We are pleased to announce that we have awarded two new Business Interaction Vouchers.

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Dr Pandhal, The University of Sheffield and Celbius – Acoustical modifications to increase recombinant glycoprotein expression from engineered E. coli cells

​The demand for protein therapeutics is increasing with the human population, which is predicted to top 9 billion by mid-century. In addition, the biopharmaceutical industry landscape is changing as a result of shifting customer demographic (e.g. higher population increases in less developed countries), the rise in potential for personalised medicine (i.e. a move to manufacture smaller volumes and more diverse libraries of drugs) and the increasing availability of drug biosimilars as patents for big blockbuster drugs come to an end. A majority of the complex drugs are currently produced in mammalian cell lines, where rapid advances in cultivation techniques have improved productivity. However, these cell lines are expensive to grow and more difficult to manipulate genetically. This means that expanding the toolbox of simpler, easier-to-control and manipulate production cell lines, for example E. coli, is particularly desirable and timely. E. coli is currently used to make simple drugs like insulin but work is underway to enhance the capability of these cells to modify proteins with the addition of specific sugars (complex drugs) or provide a site specific attachment molecule for in vitro modifications. Unfortunately the process is very inefficient and requires massive improvement in cell line ability as well as process technologies. This project proposal aims to combine the expertise of the industrial partner in ultrasonication methodologies and the PI’s skills in glycoprotein production in bacteria, with the application of ultrasonic frequencies to improve not only growth of E. coli cells but also the transfer of lipid-linked sugars and proteins across internal membranes. Ultimately this could improve the productivity of E. coli cells where a larger proportion of total recombinant proteins have the required sugar modification. A range of ultrasonic frequencies will be tested using a specific E. coli cultivation rig incorporating ultrasonic waves.

Dr Alan Goddard, The University of Lincoln and Green Biologics Ltd – In vitro and in silico models of n-butanol-membrane interactions

For nearly 100 years, Clostridia bacteria have been used to make valuable chemicals including acetone, butanol and ethanol.  Purification of these products can be both difficult and expensive, but can be made easier and cheaper by increasing their concentrations in the fermentation broth.  The problem with this is that the products can be toxic to the bacteria which produce them; any mechanism which provides protection to the bacteria is highly desirable.  It is also largely unknown how the bacteria export the solvents from where they are made inside the cell.

Bacteria are surrounded by a membrane made of phospholipids and one mechanism bacteria use to protect themselves from toxicity is to change the lipid composition of this membrane.  This may well provide a viable approach to protecting cells but is very difficult to do in cells.  Ideally, it would be beneficial to know exactly which changes are protective before modifying the bacteria.  To do this, we will test isolated membranes which separate two liquid chambers to model n-butanol movement across membranes.   In concert with this, we will use computer simulations of membranes to model both the direct interaction of n-butanol with membranes and its movement across them.  This will allow us to establish a system in which we can investigate the protective effect of changing the membrane content.  In the long term, these changes can be applied to living bacteria to improve the production of these valuable biofuels.

 

New CBMNet funded projects awarded

We are pleased to announce that we have awarded two new Proof of Concept awards and one Business Interaction Voucher.

The University of Nottingham will be working with Croda Europe on the project ‘Solid state NMR analysis of lipid/surfactant interactions’, funded through a CBMNet Business Interaction Voucher.

Surfactants, including soaps, are compounds, the molecules of which possess a dual affinity for water, both attracting and repelling it. They disrupt lipidic structures, such as the membranes of bacteria and higher organisms alike. In this proposal, we aim to investigate the effect of bioproduced industrial surfactants on lipid bilayers, membrane models, to understand the mechanisms of surfactant function, to understand and optimise stability of
bioproduction and to gain insights into cellular stability in the presence of these surfactants. To achieve this, we will use advanced analytical methods, including solid state nuclear magnetic resonance (NMR), to investigate the stability of lipid bilayers in the presence of varied amounts of surfactant. Spectra, obtained from naturally present phosphorus atoms in the membranes, provide a sensitive tool for quantitative assaying of lamellar to non-lamellar conversion in the presence of surfactants.

The University of York, along with TeeGene Biotech Ltd and Johnson Matthey will be working on the project ‘Plants as Nanoparticle Producers’, funded through a CBMNet Proof of Concept Grant.

Platinum group metals (PGMs) are used in many industrial applications, often as nanoparticles (NPs). PGMs are rare materials, making them highly valuable, but their increasing dispersal in the environment is of growing concern. The metal accumulating ability of plants can be used to capture metals from the environment. Furthermore, our studies demonstrated that plants can produce PGM-NPs which can make high-performing plant-based catalysts, either in their native state or after modification. These high value products could help satisfy demand for precious metals in industry and medicine. However, the full potential of plants as PGM accumulators is yet to be realised and will critically depend on the mechanism for PGM uptake, an area of great controversy. The aim of this study is to establish whether PGM uptake in plants is via passive diffusion or mediated by (specific) proteins.

The University of Lincoln, along with Green Biologics Ltd will be working on the project ‘Identifying and characterising protective lipid changes under solventogenic stress’, funded through a CBMNet Proof of Concept Grant.

Solventogenic Clostridia are used by Green Biologics Ltd (GBL) to generate n-butanol from a variety of feedstocks providing sugars for fermentation.  n-Butanol is expensive to purify from the fermentation broth but the cost of in situ solvent removal is greatly decreased by fermenting to higher concentrations of n-butanol.   One particular challenge is that n-butanol is toxic to Clostridia at concentrations in excess of ~2% and metabolism slows down at substantially lower butanol concentrations.  A previous BIV between Alan Goddard (AG) and GBL determined that n-butanol directly disrupts model lipid bilayers made from extracted Clostridia membranes.

It has been reported that a number of changes in lipid composition of the plasma membrane occur in response to n-butanol production.  One specific class of lipids, plasmalogens, are potentially important in this process and have been shown to be upregulated in Clostridia under solventogenic stress.  Plasmalogens are ether phospholipids characterized by a vinyl ether linkage at the sn-1 position and an ester linkage at the sn-2 position and may influence the structure and function of the membrane when exposed to stresses such as n-butanol.  Using lipidomics expertise developed by Professor Ian Graham (IG) and Dr Tony Larson (TL) at the University of York, this proposal aims to determine the specific changes in plasma membrane lipid composition during n-butanol formation and to investigate their effects on membrane stability in the presence of n-butanol with a view to being able to modulate this system for enhanced biofuel production.

 

CBMNet Members Awarded IB Catalyst Funding

Congratulations to CBMNet members Green Biologics, FujiFilm Diosynth, Centre for Process Innovation, and Ingenza, who were amongst the UK companies and universities to be awarded Industrial Biotechnology Catalyst funding in the most recent round.

A total of 23 projects, ranging from making biofuel from household waste to using bacteria to make the building blocks for new medicines, will share almost £20 million from the IB Catalyst – introduced in January 2014 to support collaboration between UK researchers and the emergent industrial biotechnology sector.

See full story here.