Industrial biomanufacturing: The future of chemical production

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Science  06 Jan 2017:
Vol. 355, Issue 6320, aag0804
DOI: 10.1126/science.aag0804

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The next era of chemical manufacturing

Producing mass quantities of chemicals has its roots in the industrial revolution. But industrial synthesis leads to sizeable sustainability and socioeconomic challenges. The rapid advances in biotechnology suggest that biological manufacturing may soon be a feasible alternative, but can it produce chemicals at scale? Clomburg et al. review the progress made in industrial biomanufacturing, including the tradeoffs between highly tunable biocatalysts and units of scale. The biological conversion of single-carbon compounds such as methane, for example, has served as a testbed for more sustainable, decentralized production of desirable compounds.

Science, this issue p. 10.1126/science.aag0804

Structured Abstract


Environmental, geopolitical, and economic factors are reshaping our view of global energy and manufacturing demands. Addressing these challenges may require a shift from the current model of industrial chemical manufacturing, which employs large-scale megafacilities that benefit from economies of unit scale. Contrary to the traditional approach, a model based on economies of unit number is proposed to reduce capital costs per unit capacity. Industrial biomanufacturing, which exploits biological processes for manufacturing, offers one way to address these changing global factors while using the economies of unit number model. This model employs both facility-level mass production of small-scale, modular units and improvements to process design resulting from repetition in a “learning-by-doing” approach. The lower investment and financial risk associated with smaller-scale, lower–capital cost facilities allow a larger number and more diverse group of technology players to be involved, in turn enabling faster innovation and novel technology adoption as well as a faster response to market drivers.


In contrast to current chemical manufacturing methods, characteristics inherent to bioconversion processes—such as the ability to operate at mild temperatures and pressures and achieve high carbon- and energy-conversion efficiencies in single-unit operations—result in more streamlined and less technologically complex processes. These characteristics enable flexible, smaller-scale, and capital expenditure–efficient operation that can both support and benefit from a large number of facilities, according to the economies of unit number model. For example, the capital expenditure entry-level cost of corn-grain ethanol facilities, the most widely developed current example of a bioconversion process, has substantially decreased as the number of plants has increased over the past few decades. This has facilitated rapid, small-scale, and widespread deployment resulting in a more than 10-fold increase in U.S. ethanol production from 1995 to 2015.

Advances in metabolic engineering, synthetic biology, genomics, and industrial process design have pushed industrial biomanufacturing closer to more widespread adoption. Particular emphasis on single-carbon feedstocks, such as methane or CO2, in applications where large-scale chemical manufacturing is infeasible or too costly can leverage both economies of unit number for mass production of facilities and the benefits of manufacturing automation to reduce capital expenditure per unit scale. Current research efforts focused on the design of carbon- and energy-efficient metabolic pathways have been particularly beneficial. Advances in tool development for metabolic pathway design have included in silico organism design strategies, genome mining techniques, and computational enzyme design efforts. The integration of these with systems biology techniques, such as next-generation sequencing and high-sensitivity “omics” methods, has allowed for the design and potential development of millions of chemical production pathways. The use of genome engineering technologies—such as clustered regulatory interspaced short palindromic repeats (CRISPR)–associated protein Cas9 systems and multiplex automated genomic engineering—and recent advances in screening and selecting for edited organisms using biosensors have reduced the time required to complete genomic editing to a fraction of the traditional time requirements. Automation-based process design improvements of these biotechnology advances have also facilitated rapid advances in industrial biomanufacturing.


Continued development of industrial biomanufacturing in the 21st century will require further advances in biocatalyst design and process design engineering. To facilitate a future based on industrial biomanufacturing, further development of genomic tools and industrial design automations suited to these purposes is paramount. Furthermore, reducing the time required from concept design to industrial relevance is essential. Specific developments in the area of one-carbon feedstocks stand to exploit the opportunity presented by currently wasted, distributed methane through the increased adoption of an economy of unit numbers approach in industrial biomanufacturing. Although much work remains, the future of industrial biomanufacturing holds great promise in meeting the evolving demands of chemical production in the current century and beyond.

Methane-based industrial biomanufacturing for fuel and chemical production.

Exploiting biological processes can enable the conversion of single-carbon feedstocks, like methane, to the array of chemical products currently produced through industrial chemical manufacturing with considerable economic, environmental, and societal advantages.


The current model for industrial chemical manufacturing employs large-scale megafacilities that benefit from economies of unit scale. However, this strategy faces environmental, geographical, political, and economic challenges associated with energy and manufacturing demands. We review how exploiting biological processes for manufacturing (i.e., industrial biomanufacturing) addresses these concerns while also supporting and benefiting from economies of unit number. Key to this approach is the inherent small scale and capital efficiency of bioprocesses and the ability of engineered biocatalysts to produce designer products at high carbon and energy efficiency with adjustable output, at high selectivity, and under mild process conditions. The biological conversion of single-carbon compounds represents a test bed to establish this paradigm, enabling rapid, mobile, and widespread deployment, access to remote and distributed resources, and adaptation to new and changing markets.

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