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Jan 1, 2007 (Vol. 27, No. 1)

Industrial Biotech Meets Systems Biology

Petrochemical Industry Finding Success by Turning to Biotechnology

  • Had this article been published three to five years ago, the target audience would likely have been medical, bioprocess, or pharmaceutical biotechnologists focused on applying systems biology to areas such as regulatory responses in cell signaling pathways, protein expression, or the rational design of novel therapeutic agents. Today, however, the target audience for systems biology has expanded to include biotech and bioprocess development groups. The tools of this field now impact the design of cell factories used by major bulk, intermediate, and specialty chemical manufacturing companies, often including petroleum manufacturers and refiners.

    What is the motivation behind industrial biotechnology’s recent penetration into the chemical manufacturing world? The cost of petroleum increased nearly 150% between January 2001 and 2006 from $22/bbl to $55/bbl. Global energy consumption is projected to increase by 57% to 681 trillion MJ between 2002 and 2025. The rapidly emerging economies of China, India, and Russia (2005 GDP growth rates of 9.9%, 7.6%, and 6.4%, respectively, compared to the average world GDP growth rate of 4.7%) are consuming energy sources at a record pace. These trends are driving traditional chemical manufacturing companies to fight against strong competition for their primary feedstock, petroleum.

    Petroleum products refined from crude oil are generally classified into three categories: transportation fuels, finished nonfuel products, and feedstock for the chemical industry. In 2005 more than 75% of all petroleum was converted and sold as fuel, while less than 5% served as feedstock.

    As most process development and manufacturing groups will agree, the startup of a new process often involves significant capital and operating expenses that over time, with improvements in technology, gains in operating efficiencies, and release of second-generation processes, will decrease.

    As the process matures the largest cost fraction will be the raw materials. The industry is faced with a significant challenge in identifying sustainable raw materials that can be used in cost-effective, robust, and high end-product yield, titer, productivity, and quality processes. Industrial biotechnology coupled with recent developments in the fields of systems biology and metabolic engineering is offering such processes.

  • The Beginnings of Industrial Biotech

    Industrial biotechnology, often referred to as white biotechnology in Europe, is the conversion of biomass via biocatalysis using microbial fermentation or enzyme catalysis to produce chemicals, materials, and/or energy. Here, we define biomass as an organic-based polymer resulting from photosynthetic carbon fixation (typically CO2), which in monomer form may include glucose, xylose, galactose, mannose, or similar monosaccharide.

    Industrial biotechnology is by no means a new field. Fermentation processes for antibiotics, vitamins, organic acids, and amino acids are well established.

    In each of these examples, host organisms well suited for production of the target compound were naturally isolated. Furthermore, under controlled environments, random mutagenesis followed by screening, selection, and traditional bioprocess development were used to enhance production yields, titers, productivities, and robustness. This method while providing little to no mechanistic understanding of which specific genetic perturbations lead to improved strains so that they could be further exploited, has proven to be commercially successful.

    In the late 1980s and early 1990s, with recombinant DNA technology emerging from medical biotechnology, we witnessed expression of compounds previously produced via synthetic routes now being attempted in production organisms. This was made possible by the introduction of genetic sequences encoding for enzymes that were likely to catalyze desired reactions or the deletion of genes that would down-regulate undesired reactions and pathways. These approaches were largely hypothesis driven, resource intensive, and low-throughput. Such methods thus minimized the probability of successfully identifying a genotype that would elicit a significantly improved phenotype.

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