Background n-Butyraldehyde is a high-production volume chemical produced exclusively from hydroformylation of propylene. It is a versatile chemical used in the synthesis of diverse C4–C8 alcohols, carboxylic acids, esters, and amines. Its high demand and broad applications make it an ideal chemical to be produced from biomass.ResultsAn Escherichia coli strain was engineered to produce n-butyraldehyde directly from glucose by expressing a modified Clostridium CoA-dependent n-butanol production pathway with mono-functional Coenzyme A-acylating aldehyde dehydrogenase (Aldh) instead of the natural bifunctional aldehyde/alcohol dehydrogenase. Aldh from Clostridium beijerinckii outperformed the other tested homologues. However, the presence of native alcohol dehydrogenase led to spontaneous conversion of n-butyraldehyde to n-butanol. This problem was addressed by knocking out native E. coli alcohol dehydrogenases, significantly improving the butyraldehyde-to-butanol ratio. This ratio was further increased reducing media complexity from Terrific broth to M9 media containing 2% yeast extract. To increase production titer, in situ liquid–liquid extraction using dodecane and oleyl alcohol was investigated. Results showed oleyl alcohol as a better extractant, increasing the titer of n-butyraldehyde produced to 630 mg/L.ConclusionThis study demonstrated n-butyraldehyde production from glucose. Through sequential strain and condition optimizations, butyraldehyde-to-butanol ratio was improved significantly compared to the parent strain. Results from this work may serve as a basis for further development of renewable n-butyraldehyde production.Electronic supplementary materialThe online version of this article (10.1186/s13068-017-0978-7) contains supplementary material, which is available to authorized users.

Acetyl-CoA is a key metabolite precursor for the biosynthesis of lipids, polyketides, isoprenoids, amino acids, and numerous other bioproducts which are used in various industries. Metabolic engineering efforts aim to increase carbon flux towards acetyl-CoA in order to achieve higher productivities of its downstream products. In this review, we summarize the strategies that have been implemented for increasing acetyl-CoA flux and concentration, and discuss their effects. Furthermore, recent works have developed synthetic acetyl-CoA biosynthesis routes that achieve higher stoichiometric yield of acetyl-CoA from glycolytic substrates.

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A general goal of systems biology is to acquire a detailed quantitative understanding of the life-sustaining interactions between genes and proteins. There arises an interesting question of whether these network dynamics can be controlled externally. In the open-loop approach to experimental biology, a control design would be chosen based on a desired target response and modeling with all the available knowledge about the system. If the system is not completely understood or disturbances occur, then unexpected deviations from the desired response can arise. A means to circumvent this difficulty is to optimize the controls in a closed-loop operation by modifying successive input controls based on the performance of previous controls. This paper presents a simulation of closed-loop learning control applied to biological systems in order to generate a desired response. The most powerful advantage of this technique is that the controls are deduced based on experimental results and the process can operate without a model for the underlying biochemical network. This feature eliminates the problem of faulty predictions as well as the need for a detailed understanding of the underlying molecular pathways, suggesting that biological systems can be controlled even before the post-systems biology era.

Background Butyl acetate is a versatile compound that is widely used in the chemical and food industry. The conventional butyl acetate synthesis via Fischer esterification of butanol and acetic acid using catalytic strong acids under high temperature is not environmentally benign. Alternative lipase-catalyzed ester formation requires a significant amount of organic solvent which also presents another environmental challenge. Therefore, a microbial cell factory capable of producing butyl acetate through fermentation of renewable resources would provide a greener approach to butyl acetate production. Result Here, we developed a metabolically engineered strain of Escherichia coli that efficiently converts glucose to butyl acetate. A modified Clostridium CoA-dependent butanol production pathway was used to synthesize butanol which was then condensed with acetyl-CoA through an alcohol acetyltransferase. Optimization of alcohol acetyltransferase expression and redox balance with auto-inducible fermentative controlled gene expression led to an effective titer of 22.8 ± 1.8 g/L butyl acetate produced in a bench-top bioreactor. Conclusion Building on the well-developed Clostridium CoA-dependent butanol biosynthetic pathway, expression of an alcohol acetyltransferase converts the butanol produced into butyl acetate. The results from this study provided a strain of E. coli capable of directly producing butyl acetate from renewable resources at ambient conditions.