Isobutanol keto-acid pathway

Figure 15.4 Isobutanol and 2-methyl butanol (2MB) production via keto acid pathway in cyanobacteria. Gene/protein symbols are dmA, citramalate synthase leuCD, isopropylmalate isomerase leuB, 3-isopropylmalate dehydrogenase AHAS, acetohydroxyacid synthase ilvC, acetohydroxy acid isomeroreductase ilvD, dihydroxy acid dehydratase kivd, ketoisovalerate decarboxylase yqhD, alcohol dehydrogenase.

Butanol has been synthesized in various organisms through different pathways. The CoA-dependent pathway from Clostridium and its variations (Figure 19.1) are the best studied [65]. This pathway is chemically similar to the reversal of P-oxidization [66, 67]. The intrinsic iteration nature of reverse p-oxidization also enables the biosynthesis of longer chain alcohols, for example, -hexanol and n-octonol [66]. The citramalate and threonine pathways fall into the same broad group as the keto-acid pathway (Figure 19.2), which is more commonly utihzed for isobutanol production. 

With the successful development of an isobutanol production pathway in E. coli, the a-keto-acid isobutanol production pathway was transferred to the traditional amino acid producer Corynebacterium glutamicum [89]. The native ilvCD and adhA genes were overexpressed, which led to 2.6 g 1 of isobutanol production with other alcohols as byproducts. By deleting the competing pathways, namely pyruvate carboxylase and lactate dehydrogenase, isobutanol production was increased to 4.9 g 1 . The work showed the potential of both the universality of the a-keto-acid isobutanol production pathway and the potential of utilization of C. glutamicum for higher chain alcohol production [89]. 

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