title: Metabolic engineering in chemolithoautotrophic hosts for the production of fuels and chemicals.
abstract: The ability of autotrophic organisms to fix CO2 presents an opportunity to utilize this 'greenhouse gas' as an inexpensive substrate for biochemical production. Unlike conventional heterotrophic microorganisms that consume carbohydrates and amino acids, prokaryotic chemolithoautotrophs have evolved the capacity to utilize reduced chemical compounds to fix CO2 and drive metabolic processes. The use of chemolithoautotrophic hosts as production platforms has been renewed by the prospect of metabolically engineered commodity chemicals and fuels. Efforts such as the ARPA-E electrofuels program highlight both the potential and obstacles that chemolithoautotrophic biosynthetic platforms provide. This review surveys the numerous advances that have been made in chemolithoautotrophic metabolic engineering with a focus on hydrogen oxidizing bacteria such as the model chemolithoautotrophic organism (Ralstonia), the purple photosynthetic bacteria (Rhodobacter), and anaerobic acetogens. Two alternative strategies of microbial chassis development are considered: (1) introducing or enhancing autotrophic capabilities (carbon fixation, hydrogen utilization) in model heterotrophic organisms, or (2) improving tools for pathway engineering (transformation methods, promoters, vectors etc.) in native autotrophic organisms. Unique characteristics of autotrophic growth as they relate to bioreactor design and process development are also discussed in the context of challenges and opportunities for genetic manipulation of organisms as production platforms.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Ferris State University, Big Rapids, MI, United States.
authors.forename: S Eric
authors.initials: SE
authors.lastname: Nybo
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, United States.
authors.forename: Nymul E
authors.initials: NE
authors.lastname: Khan
authors.affiliation: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Woolston
authors.affiliation: Department of Chemical Engineering, The Pennsylvania State University, University Park, PA, United States. Electronic address: wrc2@psu.edu.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Curtis
mesh_terms: D056804:Biofuels; D060847:Metabolic Engineering / Q000379:methods*; D043367:Ralstonia / Q000235:genetics / Q000378:metabolism; D016992:Rhodobacter / Q000235:genetics / Q000378:metabolism
chemical_list: D056804:Biofuels
keywords: Acetogen; Biochemicals; Biofuels; CO(2) fixation; Electrosynthesis; Genetic transformation; Hydrogenase