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The Defense Manufacturing Conference (DMC) is the nation’s largest annual forum for enhancing and leveraging the efforts of scientists, engineers, managers, technology leaders and policy makers across the defense manufacturing industrial base. This event brings together leaders from government, industry, and academia to exchange perspectives and information about critical Department of Defense (DOD) industrial base policies, sector analyses and manufacturing technology programs for the production and sustainment of affordable defense systems. This is the premier national forum for presenting and discussing initiatives aimed at addressing enhanced defense and related national manufacturing capabilities and requirements.
Todd Pray, ABPDU’s Program Director, is an invited speaker at this conference. His presentation is entitled “Rapid development and optimization of synthetic biology processes at ABPDU.”
Abstract
Complex biochemistry occurring naturally in microbial cells enable basic biomanufacturing, such as the application of Saccharomyces cerevisiae to convert glucose to ethanol. Twelve enzymes in an individual S. cerevisiae cell coordinate among themselves and generate a series of nine intermediate molecules, as if they were workers on an assembly-line in a factory that were following a predetermined protocol. This elaborate biochemistry in each living cell makes it a bio-factory in itself, with DNA being the source of protocols. Fermentation experts have long exploited these micro-biofactories by culturing them in large quantities to generate products, such as fermented foods, beverages, etc. Biologists have been manipulating the protocols by introducing DNA from other species to generate products such as penicillin, etc. Synthetic biology enables biologists with the capability of designing, editing, and generating synthetic DNA, which can be integrated in a bio-factory to generate new molecules that were previously unavailable for production through living organisms. The originality of such synthetic micro-biofactories mandates substantial research efforts in the development of the associated process-related areas. At the US Dept of Energy’s Advanced Biofuels & Bioproducts Process Development Unit (AB-PDU), located at Lawrence Berkeley National Laboratory in the San Francisco Bay Area, we perform study and develop fermentation and recovery processes to produce and purify novel bio-products through synthetic biology based biomanufacturing technologies. A key feature inherent to the expansion of synthetic biology for defense is the need for rapid prototyping, scaling and integration of production processes for a wide array of molecules and materials from diverse micro-organism types. The ABPDU specializes in this type of rapid development, optimization, and piloting in collaboration with several National Labs, academic, and industrial organizations. Over the past four-plus years, the ABPDU has worked with 40 companies using private and / or Federal funding, including as a subcontractor for an awardee of the DARPA Living Foundries Program. Across its Federal- and industry-sponsored R&D, the ABPDU has developed expertise with nearly 20 different monoculture microbial host organisms and consortium cultures. In turn, the team has produced, in rapid succession, a diverse array of chemicals and materials. These include a range of small molecules such as isoprenoid hydrocarbons; hydroxy-, amino-, organic- and fatty-acids; lipids; aromatics; ketones; lactones; esters; and alcohols which can be used as end-products or chemical intermediates to be upgraded or polymerized. The ABPDU has also worked extensively with different microorganisms for protein and enzyme production as well as for the cultivation and recovery of active biological cultures for use in therapeutic, agricultural, or nutritional applications. Finally, the use of microbial systems to generate new materials, such as biopolymers and bioplastics, has also been established at the ABPDU. In this presentation, we will describe a few representative case studies across these diverse product types and provide insights into how biological processes can be best scaled and integrated with downstream purification and analysis to most rapidly – within a few short weeks – produce critical chemicals, materials, enzymes and other active biologics for testing and use across a wide array of applications.