STEERING COMMITTEE

CHAIR

Joy Doran-Peterson, Ph.D. University of Georgia

Ashanti Johnson, Ph.D. University of Texas at Arlington, Institute for Broadening Participation

Robert Kelly, Ph.D. North Carolina State University

Stephen Van Dien, Ph.D. Genomatica, Inc.

PARTICIPANTS

Eric Abbate, Ph.D. Novozymes, Inc.

Doug Cameron, Ph.D. First Green Partners

Michael Carroll Hunt Oil

Brad Fabbri, Ph.D. Monsanto Company

Doretha Foushee, Ph.D. North Carolina Agricultural and Technical State University

Michael Guettler Michigan Biotech Institute International

Chris Guske, Ph.D. Tate & Lyle

Laura Mydlarz, Ph.D. The University of Texas at Arlington

Robert Nerem, Ph.D. Georgia Institute of Technology

Jens Nielsen, Ph.D. Chalmers University of Technology

Joseph O. Rich, Ph.D. United States Department of Agriculture, Agricultural Research Service

Jorge L.M. Rodrigues, Ph.D. University of Texas at Arlington

Elaine Shapland, Ph.D. Amyris Biotechnologies, Inc.

Bhupendra Soni, Ph.D. Marrone Bio Innovations

Gregory Whited, Ph.D. DuPont Industrial Biosciences (Genencor)

Henry N. Williams, Ph.D. Florida A&M University

AMERICAN ACADEMY OF MICROBIOLOGY STAFF

Ann Reid Director

Leah Gibbons Colloquium and Public Relations Program Assistant

Shannon E Greene, Ph.D. Colloquium Fellow

WHY NOW?

For millennia, humankind has made use of microbial capabilities. Bread, cheese, pickles, and wine are just a few of the products that, like beer, rely on microbes. In the last hundred years, microbiology has become a formal scientific discipline, through which the identities, capabilities, and cultivation requirements of many different microbes have been codified.

Until recently, in-depth study of microbes was confined to those species that could be grown in the laboratory. Lately, however, our understanding of the microbial world has exploded. With the ability to extract and sequence DNA from environmental samples — a scientific approach known as metagenomics — has come evidence that microbes are far more diverse and ubiquitous than laboratory studies previously suggested. Microbes have adapted to extreme environments like thermal hot springs, the upper atmosphere, severely polluted soil and water, permafrost, desert, and highly acidic mine drainage. Not only are microbes found throughout the environment, they also inhabit every multicellular organism, often providing essential services for their hosts. Billions of years of evolution have resulted in microbes with the capacity to liberate energy from virtually any chemical bond. Along with the ability to break down almost all chemical compounds, natural or manmade, microbes are also masters of chemical synthesis, capable of all manner of complicated, multistep synthetic processes. The spectacular metabolic, catabolic, and synthetic capacities of microbes make them a nearly infinite resource for industrial applications. If there is a chemical that you want to break down, there is probably a microbe that can do it. If there is a compound you wish to synthesize, a microbe can probably help. Already microbes are used to break down plant waste, produce pharmaceuticals, and detoxify sewage.

Another rapidly advancing area of microbiology is that of host-microbe interactions. It is becoming increasingly clear that all plants and animals are dependent on intimate, evolutionarily ancient partnerships with microbes. As these relationships become better understood, agricultural and medical applications will become possible. For example, microbes can be employed to enhance crop productivity, improve livestock health, and even prevent or cure human diseases.

Microbe-powered industry is not limited to the microbes found in nature; it can also combine capabilities from different species to “design” microbes for specific industrial purposes.

In addition to microbes' already formidable biochemical talents, another characteristic makes them an even greater resource for industry. Microbes exhibit tremendous genetic flexibility. They are capable of sharing genes with each other in a number of ways and many of these natural capabilities have been exploited in the laboratory to endow model organisms — notably yeast and E. coli — with novel or optimized metabolic or synthetic capabilities. Thus, microbe-powered industry is not limited to the microbes found in nature; it can also combine capabilities from different species to “design” microbes for specific industrial purposes. The recent, but now well-established fields of synthetic biology and metabolic engineering aim to make this kind of genetic optimization even more efficient. Efforts are underway to develop tools that allow new capabilities to be quickly and predictably inserted into microbes that can be grown at an industrial scale.

Figure

METAGENOMIC ANALYSES REVEAL EXTENSIVE MICROBIAL DIVERSITY Although high-throughput techniques to gather comprehensive information about DNA, RNA, proteins, and metabolites enable researchers to study microbes in single species communities or diverse consortia, (more...)

The future growth of the microbe-powered industrial sector depends on two crucial ingredients, both of which are now poised for rapid progress. The first ingredient is continued expansion of our fundamental understanding of the microbial world. With new technological approaches, it is becoming ever easier to discover microbes with desirable metabolic capabilities. High-throughput techniques to gather comprehensive information about the DNA, RNA, proteins, and metabolites characterizing any microbial community, paired with computational tools to make sense of the resultant huge data sets, are allowing researchers to study microbes in settings that reflect their natural environments, including mixed consortia. However, efforts to date have barely scratched the surface of microbial diversity and our understanding of how microbial communities form and function remains rudimentary. Industrial applications will require detailed understanding of the physiology and metabolism of a much more diverse group of organisms. Thus, continued basic academic research will be essential.

The second ingredient required for a microbe-powered industrial sector to thrive is translation, that is, the ability to scale up discoveries made through basic research to industrial scales. To date, we have ‘domesticated’ only a handful of model organisms. New industrial applications will require developing ways to culture and genetically manipulate a wider range of organisms. Advances in bioengineering, synthetic biology, and fermentation science are making this easier, and there is potential for great improvements in this area.

The bottom line is that the time is ripe both scientifically and technologically for the emergence of many new industries. Some may produce foods and beverages, others industrial chemicals or liquid fuels. Another group may provide microbial treatments that enhance plant growth, protect crops from drought or pests, or enhance animal health. Still another sector may produce probiotics to support human health, or microbes that deliver drugs to destroy tumors. What all these industries will have in common, though, is a dependence on microbes and therefore they will all need a microbiologically literate workforce.

BIOPOWER:

When biological material or processes are used to generate power or heat, the result is biopower. For example, burning lumber waste like sawdust or wood chips to power a generator or heat a building are examples of combustion-generated biopower. Microbes can also generate power, not through combustion, but through anaerobic digestion. In anaerobic digestion, organic materials like food waste, manure, lumber byproducts or corn stalks, are digested into simpler and simpler compounds often by several different microbes, each breaking down particular bonds. The final products of the reaction are carbon dioxide, methane, and water, or other reduced products like alcohols. Carbon dioxide and methane can be used to power generators to produce electricity and the water can be returned to the water distribution system or natural waterways. Anaerobic digestion is a good example of a microbe-powered industry that can operate successfully at different scales. Because anaerobic digestion is carried out by a consortium of microbes, careful attention to the physical and nutritional needs of the microbes is required both in the development and the operation of anaerobic digestion facilities.

According to the U.S. Environmental Protection Agency (EPA), as of 2011 there were approximately 176 anaerobic digestion systems in use in the United States, the majority of them operated by individual dairy farms, generating heat and electricity from manure. However, systems using other kinds of agricultural, lumber and food waste, and operated at larger scales by third parties are growing more common. The EPA estimates that only about 2% of livestock waste is currently being used for anaerobic digestion, so the potential for local companies operating digesters of different sizes is substantial. Anaerobic digestion is used in Europe to convert municipal solid waste to electricity, but this has not yet taken off in the United States.

A 2008 California study estimated that there was enough potential energy in the organic waste currently going to landfills to fulfill 8% of the state's electricity consumption. Much of this waste is suitable for thermal combustion, but the study estimated that high moisture-content solid waste appropriate for anaerobic digestion could produce about 15% of that electricity. Wastewater, food processing plant waste, and non-dairy farm waste are also suitable substrates for multiple scales of anaerobic digestion facilities that could provide both local jobs and power.

While anaerobic digestion is the traditional method of treatment for sewage sludge and solid wastes, microorganisms can also produce power directly via an electron-generating process called electrogenesis in a reactor called a microbial fuel cell (MFC). This direct electricity production uses microbes to cleave organic materials under anaerobic conditions and uses electrodes as final electron acceptors.

BIOBASED TRANSPORTATION FUELS:

Using microbes to break down complex carbohydrates such as cellulose and hemicellulose into the simple sugars that microbes can ferment allows a great variety of agricultural and forestry products and wastes to be converted to ethanol.

The U.S. produces over 13 billion gallons of ethanol from biomass per year, nearly all of it from corn. Corn is an efficient substrate for fermentation into ethanol because of its high sugar content, which is easily digested by yeast. Corn, however, is relatively resource-intensive to produce and using it to produce biofuel means diverting land and resources that could otherwise be devoted to food production. Using microbes to break down complex carbohydrates such as cellulose and hemicellulose into the simple sugars that microbes can ferment allows a great variety of agricultural and forestry products and wastes to be converted to ethanol. Second generation biofuels such as butanol, butanediol, and propanol; fatty acids; isoprenoids; and alkanes may ultimately be better than ethanol. Both the research to develop these new approaches and the eventual implementation of lignocellulose-based bio-alcohol production will require a workforce with microbiology expertise.

Figure

The Biomass Research and Development Technical Advisory Committee has proposed the goal of replacing 30% of the current US petroleum consumption with biofuels by 2030. In order to achieve this goal, and to support the production of commodity chemicals (more...)

BIOBASED PRODUCTS:

Over 10% of the crude oil consumed by the United States is currently used to produce industrial chemicals. With their astounding metabolic diversity, microbes could make many of these chemicals, or chemical polymer intermediates including succinate, 1,3-propanediol, 1,4-butanediol, acrylic acid, polylactic acid, isoprene, and farnesene among others, using agricultural byproducts. Replacing some crude oil with annually renewable biomass as the raw material for the production of these chemicals by microorganisms would simultaneously reduce US reliance on nonrenewable petrochemicals and encourage the growth of local biorefinery industries adjacent to current agricultural and forest lands. In some cases, these industries would be small scale and would depend on the fact that shipping the raw material is not economically viable.

The Pacific Northwest National Laboratory and the National Renewable Energy Laboratory in conjunction with the Office of Biomass Program have identified 12 top chemicals or classes of chemicals most suitable for production in a biorefinery. The chemicals were selected based their value as building blocks for downstream modification, the potential markets for the building blocks and their derivatives, and the technical complexity of the synthesis pathways.

Is there really enough biomass to make a significant dent in the amount of fossil fuels currently used for the manufacture of industrial chemicals? The Biomass R&D Technical Advisory Committee has proposed the goal of replacing 30% of the current US petroleum consumption with biofuels by 2030. In order to achieve this goal, and to support the production of commodity chemicals currently derived from petrochemicals, approximately 1 billion dry tons of biomass feedstock would be required. Currently, the agricultural and forestry sectors generate about 350 million dry tons of biological residues per year that are potentially convertible to biofuels or other bioproducts. Thus, nearly one-third of the necessary biomass to reach the Advisory Committee's goal is theoretically available.

BIOENZYMES:

While microbes themselves can be used for biotransformations of raw materials into commodity chemicals, the enzymes that do the work can also be engineered and harvested for industrial applications. Already, the large scale production of such enzymes drives a market approaching $4 billion.

“BIOFOODS”:

All plants and animals are dependent on complex communities of microbes that have evolved to provide essential services including nutrient provision and protection from pathogens.

A further opportunity exists in the area of large-scale culture of microbes that can be used to boost agricultural productivity. All plants and animals are dependent on complex communities of microbes that have evolved to provide essential services including nutrient provision and protection from pathogens. Cows digest grass only with the help of microbial communities living in their digestive tracts and plants depend on soil bacteria and fungi to provide biologically available nitrogen and phosphorus. Greater understanding of these host-microbe partnerships is opening up a promising area of research aimed at optimizing the microbial communities around crop plants and within livestock to boost productivity without the use of chemical fertilizers, conventional antibiotics, pesticides and herbicides. Local, large-scale production of microbes to be added to soil, sprayed on crops, or fed to livestock could provide viable, local business opportunities and indeed, such facilities are already in use in Venezuela and elsewhere.

Finally, consumer products like beer, wine, cheese, yogurt, and fermented foods such as soy sauce and kimchee rely on microbial activities. This sector is already growing, and has the potential to capitalize on the growing interest in sustainable, local food production and consumption, not to mention local entrepreneurship.

The National Vision for Biomass Technologies calls for the development of “a well-established, economically viable, bioenergy and biobased products industry” by 2030. Goals include doubling the share of target chemicals that are biobased, increasing the share of electricity and heat generated by biomass by 25%, and quintupling the share of transportation fuels derived from biomass. Meeting goals this ambitious will require an appropriately trained workforce.

RE-THINKING UNDERGRADUATE MICROBIOLOGY

A broader approach to undergraduate microbiology

A critical ingredient in developing a workforce for a microbe-powered industrial sector is the development of introductory undergraduate microbiology courses that provide a broad introduction to the field.

Many, perhaps most, of the students who enroll in introductory microbiology courses do so with the idea of pursuing a career in medicine. Accordingly, many undergraduate microbiology curricula focus on the health and biomedical aspects of microbiology. Students who enter college with an interest in biology but not medicine, or who drop out of the pre-medical track, are unlikely to discover that the study of microbiology can lead to many career options outside of medicine. Microbiology curricula do not generally provide a sequence of courses that would prepare a student for a career in the industrial sector. A critical ingredient in developing a workforce for a microbe-powered industrial sector is the development of introductory undergraduate microbiology courses that provide a broad introduction to the field. Such courses would lay the groundwork not only for further study of microbiology as part of biomedical education, but also for advanced study in, for example, biotechnology, biomanufacturing, fermentation science, or bioremediation. Indeed, one can imagine that instead of the current situation where pre-medicine is virtually the only undergraduate program with a microbiology component, there could be a series of majors with microbiology at their cores.

What would such a curriculum look like? Colloquium participants proposed a re-configuring of undergraduate microbiology. Introductory courses would be designed to provide a comprehensive overview of the microbial world. Ideally, students in such courses would hear from microbiologists of many different kinds, introducing them to a number of career options. With more students aware of the variety of options available, it becomes more likely that there would be sufficient demand to establish separate tracks for medical, industrial, and possibly other microbiology majors. An industrial microbiology track would include courses in:

• ▪ Microbial diversity and ecology: to make students aware of the vast metabolic potential of the microbial world.
• ▪ Microbial physiology and biochemistry: to familiarize students with essential microbial life processes, the principles of thermodynamics as they apply to microbes, and the variety of ways in which microbes interact with their environments.
• ▪ Hands-on laboratory experience with isolation, culture, fermentation, and genetic manipulation techniques for a variety of microbes: to teach students how to identify, handle, and manipulate microbes.

In addition to microbiology, quantitative skills are important for success in industry. Ideally, students should be familiar with calculus, linear algebra, statistics, large dataset management and programming. Recognizing that upper level quantitative courses as taught in mathematics departments can be a stumbling block for many biology students (and that their prerequisites can overwhelm a student's schedule), the participants appealed for the development of quantitative skills courses targeted at microbiology majors and for the incorporation of quantitative content into all microbiology classes so that students can learn to use quantitative skills in the context of biological problems and applications.

Figure

Reimagining a microbiology education with microbe-powered jobs in mind.

Ideally, an industrial microbiology track would also invite visiting speakers to discuss what working in the industry is like, and provide opportunities for site visits and internships.

Finally, whether within microbiology courses or separately, students should have opportunities to develop skills in problem-solving, experimental design, troubleshooting, and teamwork. Ideally, an industrial microbiology track would also invite visiting speakers to discuss what working in the industry is like, and provide opportunities for site visits and internships. Students graduating with such an undergraduate microbiology degree would be prepared to enter the workforce as entry-level technicians within microbe-powered companies or graduate school with an excellent grounding in industrially-relevant microbiology, quantitative skills, and problem-solving.

INDUSTRIAL MICROBIOLOGY TRACKS FOR UNDERGRADUATE ENGINEERING MAJORS

Another group of undergraduates who should be made aware of opportunities in microbe-powered industry are budding engineers. Bioengineering is a rapidly growing undergraduate major at engineering schools, but there is often a focus on biomedical applications, with biology coursework requirements skewed toward human anatomy and physiology. Another path could offer students the option of studying microbiology, genetics, molecular biology, fermentation, and process operations, while organizing guest lectures by industrial bioengineers, site visits, and industry-based internships. The same microbiology courses discussed above — focusing on microbial diversity, physiology and metabolism rather than pathology — would prepare bioengineering students for opportunities outside the medical field.

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INSTITUTIONS ARE ALREADY EXPLORING THE INTEGRATION OF BIOLOGICAL SCIENCES WITH MATHEMATICS AND ENGINEERING.

EXPANDING GRADUATE OPPORTUNITIES

NON-TRADITIONAL EDUCATION FORMATS

In addition to traditional degree programs, other formats can successfully be used to teach specialized skills or new software applications, or offer intensive introductions to new fields of study outside students' majors or employees' current responsibilities.

In addition to traditional degree programs, other formats can successfully be used to teach specialized skills or new software applications, or offer intensive introductions to new fields of study outside students' majors or employees' current responsibilities. Conceived and marketed as “boot camps,” such focused approaches make it possible for current students, recent graduates, professionals seeking re-training, and others to pick up new skills quickly. Some disciplines, especially molecular biology, have had long and successful experience with interdisciplinary summer courses such as those offered at Cold Spring Harbor. Both students and faculty praise these courses for the multi-generational, multi-disciplinary and highly collaborative atmosphere that provide tangible benefits to all participants. The contribution of full immersion summer courses to the education of the microbiologists of the future was explored in a report by the American Academy of Microbiology in 2011, which highlighted the track record of such courses in changing the lives of their participants, and the ripple effect of those changed lives on the progress of the microbial sciences. The development of similar offerings for microbe-powered industry could be an extremely efficient way to generate a cadre of appropriately trained scientists and engineers.

SCIENTIFIC AND TECHNOLOGICAL ADVANCES

A fundamental requirement for the success of a microbe-powered industrial sector is a well-filled pipeline of scientific and technological advances.

A fundamental requirement for the success of a microbe-powered industrial sector is a well-filled pipeline of scientific and technological advances, and this pipeline begins in the academic microbiology research laboratories that explore microbial diversity, physiology, evolution, and ecology and the academic engineering laboratories that push the edges of microscopy, microfluidics, single-cell manipulation, spectroscopy, and other means of observing and manipulating microbes. In addition to academic research focused primarily on basic questions with relevance for human health, research on fundamental microbiological questions of relevance to agriculture, biotechnology, and bioenergy would not only make the discoveries that drive commercial innovation, but also provide excellent training opportunities for students who will eventually populate the field.

The fields of synthetic biology, metabolic engineering, computational biology, and microbial ecology all have much to offer the emerging sector of microbe-powered industry, so investment in basic research in these areas will likely have rapid practical benefits. Support for the development and accessibility of enabling technologies that support these fields, such as high-throughput sequencing, proteomics, and microfluidics, will also have ripple effects through academia and the private sector. A few areas were highlighted as particularly useful:

• ▪ Development of more and different model organisms — full sets of tools for genetic manipulation and large-scale culture are available for only a few organisms, notably yeast and E. coli. Versatile as these organisms are, a wider range of “chassis” organisms, upon which multiple applications could be built, would be especially useful.
• ▪ Advances in modeling — coaxing microbes to produce a precise product at high concentration requires a sophisticated understanding of the complex feedback loops that govern gene expression, translation, secretion and other metabolic processes.
• ▪ Understanding microbial consortia — in nature, microbes are virtually never found in “pure culture.” Instead, they usually live in complex communities within a web of relationships: some competitive, some cooperative. It is challenging to engineer individual microbes to carry out the complex reactions of which consortia are capable. However, we know too little to engineer consortia.

GREATER COMMUNICATION AND COLLABORATION BETWEEN ACADEMIA AND INDUSTRY

Basic advances in these areas are likely to be made within academia, but partnerships between industry and academic laboratories would help discoveries get into the commercial sector more rapidly. The potential benefits of making it easier for academia and industry to cooperate have been pointed out in several recent reports. Two reports from the National Research Council (A New Biology for the 21^st Century and Research at the Intersection of Physics and the Life Sciences) and one from the American Academy of Arts and Sciences (ARISE II) all note that tremendous opportunities for advances exist at the intersections between fields, particularly between biology and the physical and computational sciences and engineering. They also discuss the value of facilitating new kinds of cooperative arrangements between academia and the private sector to speed the translation of basic research results into commercially viable products and processes. Progress at the societal level in encouraging these new opportunities will be crucial to the emergence of a thriving microbe-powered industrial sector. At the same time, this sector can serve as model for how disciplines and sectors can work together both to advance knowledge and create new economic opportunities. In 2012, two White House reports (The Bioeconomy Blueprint and the President's Council of Advisors on Science and Technology (PCAST) Report to the President on Agricultural Preparedness and the Agriculture Research Enterprise) highlighted the opportunities for economic development in rural areas based on biotechnology applications.

REGULATORY ISSUES, SAFETY, AND PUBLIC ENGAGEMENT

Acceptance of these new technologies depends on engaging local stakeholders as early as possible so that questions of safety, risk and regulation can be openly discussed.

There is one more set of issues that affects the entire biotechnology industry, including the microbe-powered industrial sector discussed in this report. Like any emerging technology, the use of microorganisms to carry out industrial-scale reactions raises questions of safety and risk. Do these microbes or the byproducts of their reactions pose a health risk? If the microbes are genetically engineered, could their intentional or unintentional release pose a risk to native organisms? If risks are identified, what constitutes an appropriate regulatory and oversight framework? Acceptance of these new technologies depends on engaging local stakeholders as early as possible so that questions of safety, risk, and regulation can be openly discussed. All training programs aimed at developing a workforce for the microbe-powered industrial sector should include exploration of relevant safety as well as ethical, legal, and social implications (ELSI) issues.

WHAT COULD MICROBE-POWERED INDUSTRIES DO?

• ▪ Biomass R&D Technical Advisory Committee assessment of potential agricultural and forestry resources to reduce petrochemical use by 30%: http://www1.eere.energy.gov/bioenergy/pdfs/billion_ton_update.pdf
• ▪ American Academy of Microbiology report on How Microbes Can Help Feed the World: http://bit.ly/FeedTheWorldReport

EDUCATING THE WORKFORCE FOR MICROBE-POWERED INDUSTRY

• ▪ Applied Biology and Biomedical Engineering Program at Rose-Hulman Institute of Technology: http://www.rose-hulman.edu/academics/academic-departments/applied-biology-biomedical-engineering.aspx
• ▪ UGA Master's in Biomanufacturing and Bioprocessing Program: http://www.biomanufacturing.uga.edu/index.php
• ▪ ASM guidelines for introductory microbiology curricula: Merkel, S. (2012). “The development of curricular guidelines for introductory microbiology that focus on understanding.” J. Microbiol. Biol. Educ. 13, 32–38.

WHAT ELSE DOES THE SECTOR NEED TO THRIVE?

• ▪ American Academy of Microbiology report on Summer Courses: http://bit.ly/AAMSummerCourses
• ▪ National Research Council, A New Biology for the 21^st Century: http://www.nap.edu/catalog.php?record_id=12764
• ▪ National Research Council, Research at the Intersection of the Physical and Life Sciences: http://www.nap.edu/catalog.php?record_id=12809
• ▪ American Academy of Arts and Sciences, ARISE II: https://www.amacad.org/content/publications/publication.aspx?d=1138
• ▪ The White House National Bioeconomy Blueprint: http://www.whitehouse.gov/sites/default/files/microsites/ostp/national_bioeconomy_blueprint_april_2012.pdf
• ▪ President's Council of Advisors on Science and Technology: http://www.whitehouse.gov/sites/default/files/microsites/ostp/pcast_agriculture_20121207.pdf