Structural and chemical description of 1, 4-Butanediol

1, 4-Butanediol

1, 4-Butanediol is an organic chemical compound with the chemical formula (CAS RN: 96-48-0, C4H6O2) and a molecular weight of 86.10 g/mol. 1, 4-BD is distinguished by the presence of aliphatic alcohol as a lactone ring of Gamma-hydroxybutyrate (Barceloux, 2012)

1, 4-Butanediol chemosynthesis

1, 4-Butanediol is extracted from petrochemical precursors, mostly maleic anhydride, propylene oxide, and acetylene, and is not only an intermediate polymer but also an industrial solvent (Burk, et al., 2008). It serves as the best chain extender to most aromatic and rigid polymers (Leng & Du, 2010). It is exclusively produced from feedstocks extracted from natural gas and oil. 1, 4-Butanediol synthesis can be achieved in various schemes (WHO, 2012). The first way is the application of Reppe Synthesis chemistry which entails reacting acetylene with two formaldehyde equivalent forming 1, 4-butynediol which is then taken through hydrogenation to produce 1, 4-butanediol. An alternative means which involves esterification process and catalyzed hydrogenation reaction of maleic acid anhydride from butane can be used to synthesize 1, 4-BD (Thomas & Visakh, 2011) The second way involves using propylene oxide which is turned to an ally alcohol and then to 4, hydroxybutyraldehyde through hydro- formulation process. Finally, through hydrogenolysis of the latter, 1, 4-Butanediol is yielded (Roy & Visakh, 2015).

Biosynthesis of 1, 4-Butanediol from Escherichia coli

Looking at the significance of 1, 4-BD in the industrial field through its contribution towards massive tones of plastics, spandex fibers and polyesters on an annual basis, it is inevitable to use the polymer. To address sustainable development which involves maximizing on production the 1, 4-BD with the use of renewable organic compounds as the source and raw materials, two different pathways for its production have been developed where E. coli which is a renewable source, hosts the metabolism linking carbon and energy directly into the two pathways as shown in the diagram below.

Fig 1. The pathways involved from E. coli as the source the synthesis of 1, 4-BD.

The enzymes involved in the second and the seventh step involves naturally occurring genes in Escherichia coli while the rest involve heterologous genes induced or imported from during the synthesis process. Each step has its characteristic enzyme as follows from the first to the seventh step: 2-oxoglutarate decarboxylase; succinyl-CoA synthetase; CoA-dependent succinate semialdehyde dehydrogenase; 4-hydroxybutyrate dehydrogenase; 4-hydroxybutyryl-CoA transferase; 4-hydroxybutyryl-CoA reductase and finally alcohol dehydrogenase.

Metabolic Engineering within the Microbes and Metabolism of 1-4 BD

Biologically, though at an industrial scale, 1, 4-BD could be synthesized by using Escherichia coli. Genetic engineering is the main domain used to enable the biosynthesis of 1, 4-BD from E. coli as a host which metabolizes sugars such as sucrose, xylose, glucose, and other biomass containing the extractive elements of mixed sugar streams into 1, 4-BD. Synchrony in chemical agreement between a pure 1, 4-BD and the synthesized 1, 4-BD shows the effectiveness of the biosynthesis process (Miesel, 2003). Identification of the pathways is normally the first and crucial step. Since the engineering is still developing, two pathways are used which are: upstream enzymes which biosynthesizes 4HB from glucose and downstream enzymes to convert the 4HB to 1, 4-BD where various unique alcohol compounds and aldehyde dehydrogenases are utilized to enable vivo conversion. The 1, 4-BD pathway uses E. coli heterologous enzymes in their combination which works on their native substrates (Yim, et al., 2011). In the downstream pathway, the genes involved are cat2 and 002C which are obtained from a high-copy plasmid pZE23S. With the inclusion of M. bovis sucA gene, α-ketoglutarate route is enabled producing a significant amount of 1, 4-BD. For the production of the 1, 4-BD from heterologous carbohydrate feedstocks, sucrose is preferred since, the E. coli K-12 strains do not absorb and use it despite the fact that there is a characterization of sucrose operons of E. coli W and Klebsiella pneumoniae which contain E. coli gene and lpdA gene, respectively. The latter is 90% identical at the nuclear level to the former and characterized with anaerobic adaptability. Besides, Klebsiella pneumonia lpdA gene contains D354K mutation which reduces NADH sensitivity. The synthetic operons had genes cloned to them controlled by lac-based PA01 promoter is frequently controlled by lactose repressor protein compound and rrnB T1 transcriptional terminator.

The production process entails a redox reaction where the highly oxidized components and polysaccharides are reduced to the desired molecule (Buchholz, et al., 2012). In this process, pathways are deleted to lactate, ethanol, and formate which are the common fermentation products after which the oxidative arm of TCA is enhanced to achieve the anaerobic cultivation conditions. The transcription repression alleviation of genes encoding enzymes in the oxidative arm of TCA cycle entails deletion of the arcA gene in the ArcAB double component system. Transcription repressor is deleted on aerobically expressed genes, and R163L mutation is introduced into the gene encoding citrate synthase, gltA, so as to suppress the inhibition by NADH, thus improving TCA-cycle flux to generate ECKh-422 strain.

References

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Burk, M. J., Van Dien, S. J., Burgard, A. P. & Niu, W., 2008. Compositions and methods for thebiosynthesis of 1,4-butanediol and its precursors. San Diego: Genomatica, Inc, .

Leng, J. & Du, S. eds., 2010. Shape-Memory Polymers and Multifunctional Composites. NewYork: CRC Press (Taylor & Francis Group).

Miesel ed., 2003. Macromolecular Symposia, No. 199: Polycondensation 2002. New York:WILEY-VCH.

Roy, I. & Visakh, P. M. eds., 2015. Polyhydroxyalkanoate (PHA) based Blends, Composites andNanocomposites. Cambridge, UK: Royal Society of Chemistry.

Thomas, S. & Visakh, P. M. eds., 2011. Handbook of Engineering and Specialty Thermoplastics.New York: WILEY.

WHO, 2012. 1,4-Butanediol (1,4-BD) Pre-Review Report, Hammamet, Tunis: World HealthOrganization.

World Health Organozation, 2016. WHO Expert Committee on Drug Dependence: ThirtySeventh report, Geneva, Switzerland: World Health Organization.

Yim, H. et al., 2011. Metabolic engineering of Escherichia coli for. Nature Chemical Biology, p.9.