title: A synthetic biochemistry molecular purge valve module that maintains redox balance.
abstract: The greatest potential environmental benefit of metabolic engineering would be the production of high-volume commodity chemicals, such as biofuels. Yet, the high yields required for the economic viability of low-value chemicals is particularly hard to achieve in microbes owing to the myriad competing biochemical pathways. An alternative approach, which we call synthetic biochemistry, is to eliminate the organism by constructing biochemical pathways in vitro. Viable synthetic biochemistry, however, will require simple methods to replace the cellular circuitry that maintains cofactor balance. Here we design a simple purge valve module for maintaining NADP(+)/NADPH balance. We test the purge valve in the production of polyhydroxybutyryl bioplastic and isoprene--pathways where cofactor generation and utilization are unbalanced. We find that the regulatory system is highly robust to variations in cofactor levels and readily transportable. The molecular purge valve provides a step towards developing continuously operating, sustainable synthetic biochemistry systems.
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, California 90095-1570, USA.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Opgenorth
authors.affiliation: Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, California 90095-1570, USA.
authors.forename: Tyler P
authors.initials: TP
authors.lastname: Korman
authors.affiliation: 1] Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, Molecular Biology Institute, University of California, Los Angeles, California 90095-1570, USA [2] Boyer Hall, UCLA, 611 Charles E Young Drive East, Los Angeles, California 90095-1570, USA.
authors.forename: James U
authors.initials: JU
authors.lastname: Bowie
mesh_terms: D002070:Butadienes / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005813:Genes, Synthetic; D045782:Hemiterpenes / Q000378:metabolism; D060847:Metabolic Engineering; D009249:NADP / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D010420:Pentanes / Q000378:metabolism; D058615:Synthetic Biology
chemical_list: D002070:Butadienes; D045782:Hemiterpenes; D010420:Pentanes; C005059:isoprene; D009249:NADP