Systems metabolic engineering of Corynebacterium glutamicum for the bioproduction of biliverdin via protoporphyrin independent pathway

Table 1 Calculated ΔG⁰′ values for the reaction to produce biliverdin starting from l-glutamate

Enzymes	Reactions (substrates → products)^a	ΔG⁰’ (kJ/mol)
GltX	l-glutamate + Glu^tRNA + ATP → l-glutamyl-Glu^tRNA + AMP + PP_i	− 369.36
HemA	l-glutamyl-Glu^tRNA + NADPH + H⁺ → l-glutamate-1-semialdehyde + Glu^tRNA + NADP⁺	372.94
HemL	l-glutamate-1-semialdehyde → 5-aminolevulinate	−6.11
HemB	2 5-aminolevulinate → porphobilinogen + 2 H₂O	− 141.13
HemC	4 porphobilinogen + H₂O → hydroxymethylbilane + 4 NH₃	− 207.52
HemD	hydroxymethylbilane → uroporphyrinogen III + H₂O	−55.13
HemE	uroporphyrinogen III → coproporphyrinogen III + 4 CO₂	−14.12
HemN	coproporphyrinogen III + 2 AdoMet → protoporphyrinogen IX + 2 5′-dAdo + 2 l-methionine + 2 CO₂	− 115.27
HemY	protoporphyrinogen IX + 3 O₂ → protoporphyrin IX + 3 H₂O₂	− 622.83
HemH	protoporphyrin + Fe²⁺ → heme + 2 H⁺	244.65
HemY	coproporphyrinogen III + 3 O₂ → coproporphyrin III + 3 H₂O₂	−622.83
HemH	coproporphyrin III + Fe²⁺ → Fe-coproporphyrin III + 2 H⁺	244.65
HemQ	Fe-coproporphyrin III + 2 H₂O₂ → heme + 2 CO₂ + 4 H₂O	− 562.79
HmuO	heme + 6 Fd_red + 3 O₂ + 6 H⁺ → biliverdin + Fe²⁺ + CO + 6 Fd_ox + 3 H₂O	− 1308.16

^aAbbreviations: 5′-dAdo, 5′-deoxyadenosine; AdoMet, S-adenosyl-l-methionine; Fd_ox, oxidized ferredoxin; Fd_red, reduced ferredoxin