Enhancing 3-Hydroxybutyrate Production in E. Coli through Acetate Recycling

Prochiral hydroxy acids, including 3-hydroxybutyrate (3HB), are useful synthons for the production of a variety of pharmaceutical, fine chemical, and polymer products. Several routes have been proposed for their biological production, including the degradation of poly(3-hydroxybutyrate)¹, or by the cleavage of 3-hydroxybutyryl-CoA precursors². However, a shortcoming of these conventional approaches commonly involves the accumulation of unwanted acetate by-product, leading to reduced product yields. As an alternative approach, here we propose two alternative enzymatic routes which incorporate an organic acid co-enzyme A transferase to promote the re-incorporation of by-product acetate. In this study we compare the utility of various enzyme homologs for the construction of a robust biosynthetic pathway in an E. coli host. Productivity enhancement is compared with that of conventional approaches.

1. Tokiwa, Y. & Ugwu, C.U. Biotechnological production of (R)-3-hydroxybutyric acid monomer. Journal of biotechnology 132, 264-272 (2007).

2. Tseng, H.C., Martin, C.H., Nielsen, D.R. & Prather, K.L.J. Metabolic Engineering of Escherichia coli for Enhanced Production of (R)- and (S)-3-Hydroxybutyrate. Applied and Environmental Microbiology 75, 3137-3145 (2009).