Received: 31 March 2020 | Revised: 24 April 2020 | Accepted: 26 April 2020 DOI: 10.1002/bit.27364 PERSPECTIVE The importance and future of biochemical engineering Timothy A. Whitehead1 | Scott Banta2 | William E. Bentley3 | Michael J. Betenbaugh4 | Christina Chan5 | Douglas S. Clark6 | Corinne A. Hoesli7 | Michael C. Jewett8 | Beth Junker9 | Mattheos Koffas10 | Rashmi Kshirsagar11 | Amanda Lewis12 | Chien‐Ting Li4 | Costas Maranas13 | E. Terry Papoutsakis14 | Kristala L. J. Prather15 | Steffen Schaffer16 | Laura Segatori17 | Ian Wheeldon18 1Department of Chemical and Biological Engineering, University of Colorado, Boulder, Colorado 2Department of Chemical Engineering, Columbia University, New York, New York 3Fischell Department of Bioengineering, University of Maryland, College Park, Maryland 4Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, Maryland 5Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan 6Department of Chemical and Biomolecular Engineering, University of California, Berkeley, California 7Department of Chemical Engineering & Department of Biological and Biomedical Engineering, McGill University, Montreal, Québec, Canada 8Department of Chemical and Biological Engineering and Center for Synthetic Biology, Northwestern University, Evanston, Illinois 9BioProcess Advantage LLC, Middesex, New Jersey 10Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, New York 11Rubius Therapeutics, Cambridge, Massachusetts 12Bristol Myers Squibb, Devens, Massachusetts 13Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 14Department of Chemical & Biomolecular Engineering & the Delaware Biotechnology Institute, University of Delaware, Newark, Delaware 15Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 16Evonik Industries AG, Marl, Germany 17Department of Bioengineering, Rice University, Houston, Texas 18Department of Chemical and Environmental Engineering, University of California, Riverside, California Correspondence Timothy A. Whitehead, Department of Abstract Chemical and Biological Engineering, University of Colorado, JSC Biotechnology Today's Biochemical Engineer may contribute to advances in a wide range of Building, 3415 Colorado Avenue, Boulder, technical areas. The recent Biochemical and Molecular Engineering XXI conference CO 80305. Email: [email protected] focused on “The Next Generation of Biochemical and Molecular Engineering: The role of emerging technologies in tomorrow's products and processes”. On the basis Funding information U.S. Department of Energy, of topical discussions at this conference, this perspective synthesizes one vision on Grant/Award Numbers: DE‐AC05‐000R22725, where investment in research areas is needed for biotechnology to continue con- DE‐SC0018249; Division of Molecular and Cellular Biosciences, Grant/Award Number: tributing to some of the world's grand challenges. 1716766; National Institute of Allergy and Infectious Diseases, Grant/Award Number: KEYWORDS R01AI141452; Division of Chemical, Biochemical synthesis, bioprocess development, biomolecular engineering, individualized Bioengineering, Environmental, and Transport Systems, Grant/Award Numbers: 1802992, medicine, non‐traditional organisms, synthetic biology 1929518; Army Research Office, Grant/Award Numbers: W911NF‐16‐1‐0372, W911NF‐19‐1‐0298, W911NF1410263 Biotechnology and Bioengineering. 2020;117:2305–2318. wileyonlinelibrary.com/journal/bit © 2020 Wiley Periodicals LLC | 2305 2306 | WHITEHEAD ET AL. 1 | INTRODUCTION The field of Biochemical Engineering is vast. From its historical ori- gins in the microbial production of antibiotics in the 1940's, today's Biochemical Engineer may contribute to advances in a wide range of technical areas including biomaterials, synthetic biology, tissue en- gineering, pharmaceutical production, food science, and bioenergy, among others. The industrial biotechnology sector, traditionally the between electronics and biology of extracellular vesicles Building and exploiting interface The biology and biotechnology province of biochemical engineering, is estimated at >$100 billion per Engineering to understand and exploit new biology year in the United States with over 10% growth rate (Carlson, 2016). There are many grand challenges that will require solutions that involve biotechnology such as energy, water, waste, carbon utiliza- tion, food, healthcare, etc. The opportunities for biotechnology to positively impact life on earth have never been higher. The recent Biochemical and Molecular Engineering XXI con- based engineering ference held in Mont Tremblant, Quebec, focused on “The Next ‐ Generation of Biochemical and Molecular Engineering: The role of ” and cell emerging technologies in tomorrow's products and processes (July ‐ 2019). At this conference, a panel of biochemical engineers was protein design into a decision framework predictable cell behaviors through synthetic biology convened to discuss grand challenges for the field. The composition with data driven approaches for protein Genetically encoded biosensors Integrating computational and experimental Melding heterogeneous biological systems data Transforming cellular control and of the panel was designed to cover a range of research areas, feature Forward engineering for cellular and biomolecular control Integration of mechanistic based models speakers with variable years of experience in the field, and include academic and industrial practitioners. The panel contributed 18 to- pical areas (2 per panelist) for consideration in advance of the meeting, and conference attendees voted to select nine of these (1 per panelist) for further discussion. To aid in voting, short descriptions were provided for each topic through a polling app re- Biopharma Technology products and medical devices commended by Engineering Conferences International (ECI). Atten- individualized medicine Gene therapy: The next leap in Integrating biotherapeutic dees could also offer comments that could be read and endorsed by Bioprocess development for individualized medicine Bioprocess development for other attendees. The selected topics therefore represented the — consensus view of the attendees of the most significant option of each pair. For each selection, perspectives were offered by the panel cultures ‐ and broadly discussed by the attendees in a robust moderated dia- logue. The goal was to capture and cross‐fertilize ideas of the dif- ferent conference sessions that might contribute to emerging new modality for synthesis metabolons research areas or grand challenges. catalysis with biochemical conversion Consortia and Co Pushing past the limits of biochemical synthesis This Perspective article synthesizes these grand challenge topical Combining chemical areas to five broad thematic areas (Table 1) where concentrated efforts and focus by the field are needed, recognizing that many opportunities across the discipline exist. Perhaps the most consistent theme was the need to move beyond traditional products free production (therapeutic proteins) and model organisms/cells (Chinese Hamster ‐ Ovary [CHO], Escherichia coli, Saccharomyces cerevisiae). Many grand challenges in environmental and food sustainability, personalized model organism ‐ modalities medicinal pathways opportunities in food and beverage production health, and others, emerged that could be solved by biochemical development Point of care cell Chassis development for plant Biochemical engineering Valorization of waste streams Dynamic spatial assembly of Novel products and nontraditional organisms engineers skilled in the techniques and methodologies of modern Non biotechnology. To do so, the field must develop new tools, funding, and drivers to expand into these new areas. The prevailing sentiment was that we must push past the traditional limits of biochemical synthesis, with the paradigm of one cell type producing one product. Thematic and topical areas considered for this perspective Broad challenges, for example, within this specific thematic area in- clude: developing rules for hybrid biochemical/chemical conversion selected; Blue, unselected) Thematic areas Topical area (Green, bioprocesses; predictive control of metabolic pathway spatial TABLE 1 WHITEHEAD ET AL. | 2307 assembly; and the use of alternative biomanufacturing paradigms for many important reasons why we need to expand applied research enhancing biological conversion processes, such as microbial con- activities with non‐model cells and organisms (Figure 1). sortia, designed co‐cultures, or cell‐free systems. Other thematic areas include: bioprocess development for individualized medicine, • Alternative cells provide new opportunities for metabolic en- forward‐engineering for cellular control and predictable cell beha- gineering and synthetic biology. Non‐model cells may serve as viors, which includes data‐driven machine learning approaches for superior “chassis” organisms as they can thrive in extreme en- accelerating design, and engineering to understand & exploit new vironments and are already evolved for optimized performance of biology. various capabilities. Non‐model cells can provide different The topical areas listed below are by no means a comprehensive capabilities like stress‐tolerant phenotypes and enhanced catabolic portrait of all current activities by biochemical engineers,