Lee metbolic eng synthetic bio BME 162 GuestLecture Apr2_2012

The histogram for the exhaustive search reflects a

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Unformatted text preview: many pathways •  Each pathway is separately evaluated •  Pathway leading to zero yield are considered non ­viable 4/2/12 BME 162 Guest Lecture 33 Comparison of Weigh0ng Schemes 3.5 Maximum yield 3 2.5 2 m ean(high connectivity weighting) max (high connectivity weighting) mean(low connectivity weighting) max (low connectivity weighting) mean(uniform weighting) max (uniform weighting) 1.5 1 4/2/12 100 300 500 700 900 1100 1300 1500 Number of iterations BME 162 Guest Lecture 34 Sampling Efficiency 1 1 a 0.8 Yield Yield 0.8 0.6 0.6 0.4 0.4 0.2 0.2 0 0 1 10 20 30 Number of pathways 0 0 40 c 1 250 500 750 1000 Number of pathways 1250 5 10 15 20 Number of pathways 25 d 0.8 Yield 0.8 Yield b 0.6 0.6 0.4 0.4 0.2 0.2 0 0 10 20 30 40 Number of pathways 50 0 0 Yield distributions for fatty acid methyl ester obtained using uniform probabilistic search (a), exhaustive search (b), high-connectivity probabilistic search (c) and low-connectivity probabilistic search (d). The histograms for the probabilistic searches represent the cumulative results of 1,000 iterations. The histogram for the exhaustive search reflects a single run. 4/2/12 BME 162 Guest Lecture 35 Run0me •  ProbPath –  Pathway length capped at 23 reac0ons –  Ca. 6 minutes for 1000 itera0ons •  Quad ­Core 2.3GHz processors (AMD Optron 8356) and 64 GB physical memory •  Exhaus0ve search 4/2/12 BME 162 Guest Lecture 36 Experimental Support Metabolite name Isopentenyl diphosphate1 Native Yield 301.13 mg/gDW/hr Method Uniform probabilistic search Exhaustive search Literature #pathways 11 9 NA Max. Yield/Rate 314.24 mg/gDW/hr 314.24 mg/gDW/hr 27.4g/L amorphadiene[27] (1.95 mg/gDW/hr) Myo-inositol2 0 mol/molglucose Uniform probabilistic search Exhaustive search Literature 71 42 NA 0.2 g/g glucose 0.2 g/g glucose 0.23 g/L[23] (0.08 g/g glucose) Taxadiene3 Non-native Uniform probabilistic search Exhaustive search Literature 2 2 NA 0.06 g/g glucose 0.06 g/g glucose 1.3 mg/L[14] (0.06 mg/g glucose) 1,3-Propanediol Non-native Uniform probabilistic search Exhaustive search Literature 1 1 NA 2.19 mmol/gDW/hr 2.19 mmol...
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