In silico evolution of Aspergillus niger organic acid production suggests strategies for switching acid output

Table 5 Example solution from evolution of succinic acid production

Index	Reaction	Mutation effect	Complementation results
Index	Reaction	Mutation effect	% Fitness decrease	% Acid flux decrease	% Growth increase
444	QH₂m + 0.5*O₂m → Qm + H₂Om	UC	99.8	100	98.2
449	QH₂m + 2FERIm + 2Hm → Qm + 2FEROm + 4Ho	UC	99.8	100	98.2
213	PYR + NADH + H → LLAC + NAD	UC	85.3	86.2	19.3
84	LAC + NAD ⇔ PYR + NADH + H	LC	85.2	86.2	19.3
77	H + PYR → ACAL + CO₂	UC	77.1	77.8	9.6
265	GLCNT + ATP → D6PGC + ADP + H	UC	52.4	54.4	12.5
24	G6P + NADP → D6PGL + NADPH + H	UC	49.7	51.8	12.3
22	ATPm + PYRm + H₂Om + CO₂m → ADPm + PIm + OAm + 2*Hm	UC	18.9	22.5	14
1242	NH₄OH ⇔ NH₃ + H₂O	UC	12.8	13.8	3.5

The example solution is chosen as the best representative of the average solution and based on fitness. The mutation effect is given as UC or LC. UC corresponds to a mutation that imposes a flux constraint on the upper bound. LC corresponds to a mutation that imposes a flux constraint on the lower bound. Complementation results are given for each mutation, showing the effect on fitness, target acid flux, and growth when the mutation is complemented with the wild-type while retaining the other mutations

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