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The future of biologically inspired next‐generation factories for chemicals

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This century is expected to see a drastic acceleration of the field of industrial biology. Biotechnological processes are envisioned to facilitate the production of either highvalue compounds or materials that… Click to show full abstract

This century is expected to see a drastic acceleration of the field of industrial biology. Biotechnological processes are envisioned to facilitate the production of either highvalue compounds or materials that cannot be made by current methods, or high-volume chemicals where biological processes are more economical and resource efficient with a reduced environmental impact. Industrial manufacturing of a range of chemicals and materials will utilize both biological and chemical syntheses synergistically. Engineering biology to advance biology has consequently been identified as a top technology priority area in Europe and the United States (Friedman and Ellington, 2015). Yet, shifting manufacturing of chemicals and materials from purely petroleum-derived chemical synthesis to greener and environmentally friendly biomanufacturing processes that can operate at the same scale and with comparable cost margins is challenging. A major bottleneck is the development of innovative technologies for robust, cost-efficient and highyielding execution of a series of enzyme catalysed conversion reactions that convert one or more molecules into a desired chemical product. This contribution primarily assesses and discusses current and future contributions of microbial technologies as they relate to biomanufacturing towards “ensuring sustainable consumption and production patterns” (goal 12). Biomanufacturing processes may be performed using cell factories, cell-free processes or biocatalytic routes (Scheme 1). The cell factory route uses microbial cells and is presently the most advanced technology and preferred route for the large-scale production of chemicals that require several enzymatic transformation reactions. Microorganisms have a long tradition as cell factories and are used for the large-scale production of commodity chemicals such as organic acids, amino acids and bioactive compounds like antibiotics. Microbial cells have also been metabolically engineered for the production of many other molecules with applications as fine chemicals, chemical building blocks, fuels, food and feed additives and pharmaceuticals. So far, however, only a limited number of these microbial cell factories have achieved yields and titres at rates that make them economically viable. It turns out, rerouting cellular metabolic networks for the efficient production of, for the cell, undesirable and costly molecules is difficult and requires major engineering efforts that can take a decade or longer (Nielsen and Keasling, 2016; Clomburg et al., 2017). Multidisciplinary efforts in science and engineering are required for the realization of a robust and viable bioeconomy. Over the past two decades, we have seen tremendous technical developments in biotechnology that are the foundation for a new area of chemical manufacturing. DNA sequencing has become so inexpensive and readily accessible that now more genome sequences are deposited than individual gene. Similarly, inexpensive DNA synthesis together with efficient, commercially available DNA assembly methods has essentially eliminated classic cloning and instead enabled recoding of sequences and rapid construction and assembly of genetic parts to create gene libraries and pathways. Genome engineering using CRISRP-Cas9 has revolutionized cellular engineering. In principle, we should therefore be poised to fully exploit the chemical mastery of biology for the engineering of nature inspired chemical factories. In fact, new technologies and strategies are being created and adapted to speed up the microbial strain development process to make chemicals with yields, titres and rates that are industrially relevant. Biofoundries are developed in academic institutions and industry (Chao et al., 2017) that aim to perform iterative design, build, test and learn cycles for strain design in weeks instead of months or years (Scheme 1). Key elements of these platforms are computationally driven systems modelling, in silico pathway prediction, creation of genetic part libraries, high-throughput design and assembly of genetic constructs and analysis of strain libraries. The entire platform requires automation where data from each cycle inform the design of the next cycle *For correspondence. E-mail [email protected]; Tel. +1 612 625 5782; Fax +1 612 625 5781. Microbial Biotechnology (2017) 10(5), 1164–1166 doi:10.1111/1751-7915.12796 Funding Information National Science Foundation grant# MCB-12644429; Defense Threat Reduction Agency grant # HDTRA-15-0004.

Keywords: engineering; production; cell factories; chemical; biology

Journal Title: Microbial Biotechnology
Year Published: 2017

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