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

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.