title: Improving fatty acids production by engineering dynamic pathway regulation and metabolic control.
abstract: Global energy demand and environmental concerns have stimulated increasing efforts to produce carbon-neutral fuels directly from renewable resources. Microbially derived aliphatic hydrocarbons, the petroleum-replica fuels, have emerged as promising alternatives to meet this goal. However, engineering metabolic pathways with high productivity and yield requires dynamic redistribution of cellular resources and optimal control of pathway expression. Here we report a genetically encoded metabolic switch that enables dynamic regulation of fatty acids (FA) biosynthesis in Escherichia coli. The engineered strains were able to dynamically compensate the critical enzymes involved in the supply and consumption of malonyl-CoA and efficiently redirect carbon flux toward FA biosynthesis. Implementation of this metabolic control resulted in an oscillatory malonyl-CoA pattern and a balanced metabolism between cell growth and product formation, yielding 15.7- and 2.1-fold improvement in FA titer compared with the wild-type strain and the strain carrying the uncontrolled metabolic pathway. This study provides a new paradigm in metabolic engineering to control and optimize metabolic pathways facilitating the high-yield production of other malonyl-CoA-derived compounds.
authors: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180;Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180;
authors: Peng
authors: P
authors: Xu
authors: Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180;Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180; and.
authors: Lingyun
authors: L
authors: Li
authors: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180;Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180;
authors: Fuming
authors: F
authors: Zhang
authors: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors: Gregory
authors: G
authors: Stephanopoulos
authors: Department of Chemical and Biological Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180;Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180;Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180; and koffam@rpi.edu.
authors: Mattheos
authors: M
authors: Koffas
mesh_terms: D053898:Biosynthetic Pathways; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism; D005227:Fatty Acids / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D008316:Malonyl Coenzyme A / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029968:Escherichia coli Proteins; C067955:FAPR protein, E coli; D005227:Fatty Acids; D014157:Transcription Factors; D008316:Malonyl Coenzyme A
keywords: biofuels; dynamic metabolic control; transcriptional regulation