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Chapter 41 : Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism

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Abstract:

This chapter presents a summary of examples in which various metabolic engineering strategies were employed to improve microbial production of small molecules having a range of commercial value (commodity and fine chemicals). Specifically, notable achievements in engineering the biotechnological workhorse organism for chemical production are described. In terms of commodity chemicals, metabolic engineering has found the most application and success toward the production of small organic acids and amino acids (perhaps with the exception of engineering to produce 1,3- propanediol from glucose), owing largely to the natural coupling between growth and production of the compounds through fermentation. Recent progress in microbial production of acetate, pyruvate, lactate, and succinate is also described followed by examples of increased amino acid production. Organic acids including acetic acid, pyruvic acid and lactic acid have been discussed in the chapter. A variety of amino acids find applications in industries including food, animal feed, pharmaceuticals, and cosmetics. Considering the low titers of amino acids obtained from wild-type cultures, improvements of the host through metabolic engineering have been impressive. Isoprenoids (or terpenoids) represent a wide variety of specialty and pharmaceutical compounds synthesized biologically by the assembly of two or more branched, five-carbon isopentenyl pyrophosphate (IPP) subunits. and mechanisms of inhibition.

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41

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Aromatic Amino Acids
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Acetyl Coenzyme A
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Amino Acid Synthesis
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Chemicals
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Figures

Image of FIGURE 1
FIGURE 1

primary metabolic pathways involved in production of acetate, pyruvate, lactate, and succinate. Relevant genes are listed with the corresponding transformation catalyzed. ~P represents utilization or production of ATP. Genes encoding pyruvate carboxylase and -specific lactate dehydrogenase are labeled with an asterisk to indicate that they are not native to

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41
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Image of FIGURE 2
FIGURE 2

-Alanine production from pyruvate by alanine dehydrogenase ().

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41
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Image of FIGURE 3
FIGURE 3

Engineering the cysteine biosynthetic pathway (starting from serine) for production of unnatural amino acids (AA). The -acetylserine sulfhydrylases encoded by and utilize sulfide as a cosubstrate to produce cysteine, but the enzymes have relaxed specificity such that addition of select, nonnative nucleophiles (R-H) results in production of unnatural amino acids. encodes a feedback-resistant variant of serine acetyltransferase.

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41
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Image of FIGURE 4
FIGURE 4

Engineered biosynthesis of shikimic acid, quinic acid, and MA from the aromatic amino acid synthesis pathway. PCA, protocatechuic acid.

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41
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Image of FIGURE 5
FIGURE 5

Biosynthesis of 2,3--CHD starting from chorismate. The genes , and encode isochorismate synthase, isochorismatase, and 2,3-dihydroxybenzoate synthase, respectively, which catalyze the corresponding reactions depicted.

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41
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Image of FIGURE 6
FIGURE 6

(a) Two different pathways to IPP; (b) pathways to carotenoids.

Citation: Cirino P. 2010. Metabolic Engineering Strategies for Production of Commodity and Fine Chemicals: as a Platform Organism, p 591-604. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch41
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