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

• Published in: Biotechnology and bioengineering Vol. 99; no. 6; pp. 1392 - 1406
• Main Authors: Efe, C, Straathof, Adrie J.J, van der Wielen, Luuk A.M
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.04.2008; Wiley; Wiley Subscription Services, Inc
• Subjects: 4-Butyrolactone - chemistry; 4-hydroxybutyrate; Aldehydes; Biochemistry; Biochemistry - methods; Biological and medical sciences; Bioreactors - microbiology; Biotechnology; Candida - metabolism; Candida antarctica; Candida antarctica lipase; Computer Simulation; Fundamental and applied biological sciences. Psychology; gamma-butyrolactone; Glucose; Glucose - metabolism; Hydroxybutyrates - metabolism; Lactones - chemistry; lactonization; Models, Biological; pathway; Petrochemicals; Petroleum production; Signal Transduction - physiology; Studies; thermodynamics; 4-hydroxybutyrate; candida antarctica; Enzyme; Triacylglycerol lipase; Lactone; Esterases; Carboxylic ester hydrolases; Fungi; Thermodynamics; Production; Hydrolases; lactonization; pathway; gamma-butyrolactone; Fungi Imperfecti; Candida antarctica lipase
• ISSN: 0006-3592; 1097-0290; 1097-0290
• DOI: 10.1002/bit.21709

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. Biotechnol. Bioeng. 2008;99: 1392-1406.