Lee metbolic eng synthetic bio BME 162 GuestLecture Apr2_2012

Appl environ microbiol 2008 74123634 43 4212 bme 162

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Unformatted text preview: s of these modes 4/2/12 BME 162 Guest Lecture 20 EFM Representa0on of Metabolic State MFA r1 r2 r3 r4 10 5 w1 3 5 r5 r6 EMA 2 w2 7 w3 [ v1 v 2 v3 v 4 v5 v 6] = w1[1 1 1 0 0 0] + w 2[1 0 0 1 0 1] + w 3[1 1 0 0 1 1] 4/2/12 BME 162 Guest Lecture 21 A metabolic network may harbor non ­obvious EFMs Monosaccharide metabolism in E. coli 4/2/12 BME 162 Guest Lecture 22 Systema0c decomposi0on reveals several elementary flux modes P1 P4 4/2/12 P2 P5 P3 P6 BME 162 Guest Lecture P7 23 Elementary mode analysis could be used to engineer a “minimal cell” for ethanol produc0on Trinh CT et al. Appl Environ Microbiol. 2008. 74(12):3634-43. 4/2/12 BME 162 Guest Lecture 24 Decrease in Number of Modes with Gene Dele0ons 4/2/12 BME 162 Guest Lecture 25 Is there a systema0c way to iden0fy the knockouts? Boghigian BA, Shi H, Lee K, Pfeifer BA. BMC Syst Biol. 2010. 4:49. 4/2/12 BME 162 Guest Lecture 26 Tradeoff between Biomass and Synthesis Yields 4/2/12 BME 162 Guest Lecture 27 Evolu0onary Improvement 4/2/12 BME 162 Guest Lecture 28 4/2/12 BME 162 Guest Lecture 29 Iden0fica0on of Novel Synthesis Pathways •  Need for a computa0onal approach –  More than 1,000 prokaryo0c genomes fully sequenced and annotated. –  Par0al or drac genomes are available for more than 6,000 species. –  Total number of reac0ons listed in the Kyoto Encyclopedia of Genes and Genomes (KEGG) exceeds 8000 •  Op0miza0on ­based approaches –  Computa0onally expensive •  Probabilis0c approaches –  Require heuris0cs –  Need to establish sampling efficiency and diversity 4/2/12 BME 162 Guest Lecture 30 Probabilis0c Pathway Construc0on (ProbPath) •  Recursive tree construc0on –  Start from the target metabolite, i.e. synthesis product, as the root of the tree. –  Reac0on selecte...
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