Enhancement of (R)-1,3-butanediol production by engineered Escherichia coli using a bioreactor system with strict regulation of overall oxygen transfer coefficient and pH

Abstract

(R)-1,3-butanediol ((R)-1,3-BD) is an important substrate for the synthesis of industrial chemicals. Despite its large demand, a bioprocess for the efficient production of 1,3-BD from renewable resources has not been developed. We previously reported the construction of recombinant Escherichia coli that could efficiently produce (R)-1,3-BD from glucose. In this study, the fermentation conditions were optimized to further improve 1,3-BD production by the recombinant strain. A batch fermentation was performed with an optimized overall oxygen transfer coefficient (82.3 h−1) and pH (5.5); the 1,3-BD concentration reached 98.5 mM after 36 h with high-yield (0.444 mol (mol glucose)−1) and a high maximum production rate (3.63 mM h−1). In addition, a fed-batch fermentation enabled the recombinant strain to produce 174.8 mM 1,3-BD after 96 h cultivation with a yield of 0.372 mol (mol glucose)−1, a maximum production rate of 3.90 mM h−1, and a 98.6% enantiomeric excess (% ee) of (R)-1,3-BD.

Production of C2–C4 diols from renewable bioresources: new metabolic pathways and metabolic engineering strategies

“…2,3-BDO is considered as a potential platform chemical which can be used as biofuel and a building block for the synthesis of 2-butanone [ 82 ], 2-butanol [ 83 ], and 1,3-butadiene [ 84 ]. 1,3-BDO is widely used as a solvent in food and cosmetic industries [ 85 ]. 1,2-BDO is used to produce polyester resins and plasticizers.…”

“…Most of the C4 diols (1,4-BDO, 1,3-BDO, and 1,2-BDO) are non-natural metabolites which lack natural synthetic pathways. In recent years, different new pathways have been proposed for the synthesis of 1,4-BDO and 1,3-BDO [ 81 , 85 , 86 ]. Especially, biological production of 1,4-BDO from sugars has been commercialized by Genomatica [ 23 ].…”

“…One non-natural pathway for 1,3-BDO production has been proposed recently (route ① of Fig. 7 ) [ 85 , 113 ]. In this pathway, acetyl-CoA is first transferred to acetoacetyl-CoA by acetyl-CoA acetyltransferase, which is further converted to 1,3-BDO by three reduction steps catalyzed by acetoacetyl-CoA reductase, 3-hydroxybutyryl-CoA dehydrogenase, and 1,3-BDO dehydrogenase.…”

In vitroprototyping and rapid optimization of biosynthetic enzymes for cellular design

“…45 These enzymes have previously been shown to reduce a range of carboxylic acids to their corresponding aldehydes and alcohols through reduced ferredoxin. 15, 46 While the (R)-(-)-form of 1,3-BDO has been produced via other routes, [47][48][49] when using the C. kluyveri-derived Hbd we also detected the (S)-(+)-form of 1,3-BDO as determined by chiral analysis, which to our knowledge has never been produced in a biological system before. This chiral specificity is determined by the chosen 3-hydroxybutyryl-CoA dehydrogenase.…”

1,3-Butanediol Dibenzoate

“…We therefore tried using bioethanol as a starting material in an environmentally friendly synthesis reaction to obtain 1,3-butanediol (2), which is used in large quantities and is a very important industrial raw material [7,8]. 1,3-Butanediol (2) can be synthesized from ethanol using the following steps:…”