Citramalate pathway

Methyl-butanol (2MB) is synthesized via the isoleucine pathway (Figure 15.4), which is similar to the valine biosynthesis pathway. One of the challenges for 2MB production is that it passes over the same cassette of genes as in isobutanol production. A recent study [106] indicated that enhancing the citramalate pathway to direct the carbon flux from pyruvate to a-ketobutyrate led 2MB production to about 200 mg 1" with minimum side products such as 1-propanol and isobutanol. 

Over citramalate pathway (Fig. 2—right-hand side)... 

While the 2-oxobutyrate needed for isoleucine formation is shown as originating from threonine in Eig. 24-17, bacteria can often make it in other ways, e.g., from glutamate via p-methylaspartate (Eig. 24-8) and transamination to the corresponding 2-oxoacid. It can also be made from pyruvate by chain elongation using acetyl-CoA (Eig. 17-18) citramalate and mesa-conate (Eig. 24-8) are intermediates. This latter pathway is used by some methanogens as are other alternative routes. The first step unique to the biosynthetic pathway to leucine is the reaction of the... 

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. 

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