SCIENCE science.orgPHOTO: BERKELEY LAB/ROY KALTSCHMIDT
By Bradley W. Biggs^1 , Hal S. Alper^2 ,
Brian F. Pfleger^3 , Keith E. J. Tyo^1 , Christine
N. S. Santos^4 , Parayil Kumaran Ajikumar^4 ,
Gregory Stephanopoulos^5T
he industrial biotechnology sector—
commercial-scale manufacturing of
chemical products by use of cellular or
molecular biocatalysts—lies at a cross-
roads. Metabolic engineering aided by
tools of systems and synthetic biology
has expanded the scope of possible chemical
products that can be made with this approach
and the avenues available for improvements
in strain engineering. Academic interest is
strong and growing, with several high-profile
demonstrations of metabolic engineering ( 1 ,
2 ). However, few academic successes have be-
come commercial successes. The low success
rate of translating research stifles job growth,
prevents new products from reaching con-
sumers, and leaves societal and ecological
benefits of industrial biotechnology unreal-
ized. We highlight three key areas that need
greater attention, recognition, and support:
(i) policy to promote translational science
and prioritize sustainability, (ii) investment
in technology and infrastructure to enable
translational research and education, and
(iii) prioritization of biomanufacturing work-
force training and education.Industrial biotechnology is especially
suited for applications with favorable sus-
tainability metrics because of the ability of
biological systems to handle a variety of re-
newable feedstocks, including complex and
heterogeneous feedstocks such as nonfood
plant biomass ( 3 ) and single-carbon gasses
( 4 ). Because the specificity of enzymes can
enable one-pot synthesis of complex chemi-
cals ( 5 ), biological processes can produce sub-
stantially less waste and require less energy
when compared with multistep chemical
synthesis ( 6 ). Together, these advantages—if
successfully leveraged—could provide secu-
rity for material goods supply, environmental
benefits in chemical product synthesis, and
even the potential for the synthesis of new
chemicals with broad new uses as materials
and medicines.POLICY
Industrial biotechnology competes with
chemical processing, a multitrillion-dollar
industry with strong patent protection, a
well-trained workforce, economies of scale,
and depreciated facilities. Environmental
sustainability, a main advantage of industrial
biotechnology, is commonly undervalued by
society and regulators. If valuation does not
incorporate the ecological impact of the ap-
proach to chemical or biochemical synthesis,
industrial biotechnology will be relegated to
only the markets and products that cannot
be feasibly obtained any other way. High-vol-
ume, low-margin products such as polymers,
industrial chemicals, and fuels will continue
to be produced through traditional chemical
processing, forfeiting the sustainability ben-
efits of industrial biotechnology.One solution would be to require any
synthesis process (chemical or biological) to
restore the environment to its original state,
from before the synthesis process, including
gases used and generated. Requiring equal
life-cycle impact for the two approaches could
help balance competition between chemi-
cal and biological processes for high-volume
chemicals while improving environmental
conditions regardless of which approach
is ultimately used. Currently, more than 40
countries account for greenhouse gas emis-
sions, as determined from life cycle analysis,
to ensure that new, sustainable commercial-
ization efforts are on a level playing field with
mature, higher-emission businesses (7).
Emerging technologies without an estab-
lished pipeline to commercialization can
have a difficult time acquiring funding for
initial technological translation of academic
discoveries because existing funding sources
can either have too low of a risk tolerance
or misaligned funding priorities. This is the
case for synthetic biology and metabolic
engineering, with the science progressing
much faster than is the infrastructure for
translating fundamental discovery. This
type of early-stage research translation has
special requirements, including funding
through small, targeted grants to surgically
tackle key initial questions and funding of
multidisciplinary solutions that aim to re-
duce risk in the integrated system and solve
complex problems. For example, many in-
dustrial biotechnology processes are built
on a handful of microbial strains (chassis).
Understanding, at a mechanistic level, the
cellular response to the difference in stress
conditions between the laboratory and scale
would be broadly useful to the field.
This can be accomplished with existing
funding structures when properly modi-
fied to address various shortcomings. For
example, in the United States current Small
Business Innovation Research and Small
Business Technology Transfer research grant
structures make formation of a company
compulsory, which does not allow for explo-
ration before company formation of the in-
dustrial potential of a technology. Although
this mandate is satisfied by various compa-
nies, we can envision many technologies that
are not ready for company formation yet
show great commercialization potential if
some outstanding risks were removed. Once
risk is adequately reduced, such technologies
can move further toward commercializationBIOTECHNOLOGYEnabling commercial success
of industrial biotechnology
Commercial-scale research translation has been muted
(^1) Department of Chemical and Biological Engineering,
Northwestern University, Evanston, IL, USA.^2 McKetta
Department of Chemical Engineering, University of Texas
at Austin, Austin, TX, USA.^3 Department of Chemical and
Biological Engineering, University of Wisconsin–Madison,
Madison, WI, USA.^4 Manus Bio, Cambridge, MA 02138, USA.
(^5) Department of Chemical Engineering, Massachusetts
Institute of Technology, Cambridge, MA 02142, USA.
Email: [email protected]; [email protected]
These 300-liter tanks can be used to mix and sterilize
media prior to fermentation, or to mix buffers and
hold material generated in downstream processing,
at the Advanced Biofuels and Bioproducts
Process Development Unit, part of Lawrence
Berkeley National Laboratory.
POLICY FORUM
24 DECEMBER 2021 • VOL 374 ISSUE 6575 1563