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Options for biochemical production of 4-hydroxybutyrate and its lactone as a substitute for petrochemical production.

Efe C, Straathof AJ, van der Wielen LA

Department of Biotechnology, Delft University of Technology, Julianalaan 67, Delft, The Netherlands.

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.

Published 4 March 2008 in Biotechnol Bioeng, 99(6): 1392-406.
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