Metabolic engineering of Corynebacterium glutamicum for de novo production of 3-hydroxycadaverine

Functionalization of amino acids and their derivatives opens up the possibility to produce novel compounds with additional functional groups, which can expand application spectra. Hydroxylation polyamide building blocks might allow crosslinking between molecular chains by esterification. Consequently, this alter properties resulting polymers. C. glutamicum represents a well-known industrial workhorse has been used extensively lysine derivatives. These are as for chemical pharmaceutical applications. In study, it was shown first time that C3-hydroxylated cadaverine be produced de novo overproducing strain. The hydroxylase from Flavobacterium johnsoniae is highly specific its natural substrate and, therefore, hydroxylation precedes decarboxylation 4-hydroxylysine (4-HL) 3-hydroxycadaverine (3-HC). For optimal precursor supply, various cultivation parameters were investigated identifying iron concentration pH major effectors on 4-HL production, whereas supply cosubstrate 2-oxoglutarate (2-OG) sufficient. Deletion gene coding exporter LysE suggested may also involved in export structurally similar 4-HL. With optimised setting pathway extended towards 3-HC decarboxylation. Three different genes lysine/4-HL decarboxylases, LdcC CadA E. coli DCFj F. johnsoniae, expressed producing strain compared regarding production. It semi-preparative biocatalysis all three decarboxylases accept varying efficiencies. vivo, supported production best final titer 11 mM. To improve titers fed-batch 1 L bioreactor scale performed plasmid-based overexpression ldcC induced after 24 h highest 8.6 g L-1 (74 mM) reported now.