title: Options for biochemical production of 4-hydroxybutyrate and its lactone as a substitute for petrochemical production.
abstract: Options are discussed for biochemical production of 4-hydroxybutyrate (4-HB) and its lactone, gamma-butyrolactone (GBL), from renewable sources. In the first part of the study, the thermodynamic feasibility of four potential metabolic pathways from glucose to 4-HB are analyzed. The calculations reveal that when the pathways are NAD(+) dependent the intermediate succinate semialdehyde (SSA) accumulates leading to low 4-HB yields at equilibrium. For NADP(+) dependent pathways the calculated yield of 4-HB improves, up to almost 100%. In the second part of this study, continuous removal of 4-HB from the solution is considered to shift SSA conversion into 4-HB so that SSA accumulation is minimized. One option is the enzymatic production of GBL from 4-HB. Candida antarctica Lipase B shows good lactonization rates at pH 4, but unfortunately this conversion cannot be performed in-vivo during 4-HB production because of the neutral intracellular pH.
authors.affiliation: Department of Biotechnology, Delft University of Technology, Julianalaan 67, Delft, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: Efe
authors.forename: Adrie J J
authors.initials: AJ
authors.lastname: Straathof
authors.forename: Luuk A M
authors.initials: LA
authors.lastname: van der Wielen
mesh_terms: D015107:4-Butyrolactone / Q000737:chemistry*; D001671:Biochemistry / Q000379:methods; D019149:Bioreactors / Q000382:microbiology*; D002175:Candida / Q000378:metabolism*; D003198:Computer Simulation; D005947:Glucose / Q000378:metabolism*; D006885:Hydroxybutyrates / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology
chemical_list: D006885:Hydroxybutyrates; D007783:Lactones; C111420:4-hydroxybutyric acid; D005947:Glucose; D015107:4-Butyrolactone