Fig. 5

Metabolic pathways and metabolic engineering strategies for the production of 1,4-butanediol (1,4-BDO). Two metabolic pathways have been proposed to convert glucose into 1,4-BDO via succinyl semialdehyde. Route ① (illustrated by green colors) starts from succinyl-CoA, which is converted into succinyl semialdehyde by succinyl-CoA dehydrogenase. Route ② (illustrated by yellow color) starts from α-ketoglutarate, which is converted into succinyl semialdehyde by keto acid decarboxylase. Succinyl semialdehyde can be converted into 1,4-BDO in four steps. Xylose can also be converted into 1,4-BDO by two proposed pathways (route ③ illustrated by orange colors and route ④ illustrated by blue colors). To generate a 1,4-PDO hyperproducer from glucose via route ① and route ②, different byproduct synthetic pathways should be blocked as illustrated by red cross marks. adh alcohol dehydrogenase, ald 4-hydroxybutyrate-CoA reductase, adhE acetaldehyde/alcohol dehydrogenase, cat2 4-hydroxybutyrate-CoA transferase, gabD succinate semialdehyde dehydrogenase, gabT/puuE aminotransferase, 4hbd 4-hydroxybutyrate dehydrogenase, kivd α-ketoisovalerate decarboxylase, ldhA lactate dehydrogenase, mdh malate dehydrogenase, pfl pyruvate formate lyase, ppdACB glycerol dehydratase, sad succinate semialdehyde dehydrogenase, sdhABCD succinate dehydrogenase, sucD succinyl-CoA dehydrogenase, xylB d-xylose dehydrogenase, xylC d-xylonate dehydratase, xylD 2-dehydro-3-deoxy-d-xylonate dehydratase, xylX α-ketoglutaric semialdehyde dehydrogenase, yqhD NAD(P)H-dependent alcohol dehydrogenases