Chapter 10

Chapter 10: Perturbations to metabolic networks #

  1. Consider the following reaction sequence and choose the correct statement(s) about synthetic and single lethals. \[ R1: A + B \rightarrow C \]

    \[ R2: C +A \rightarrow D \] \[ R3: B + D \rightarrow E + F \] \[ R4: A + D \rightarrow E + F \] \[ R5: E + F \rightarrow Biomass \]

    a. R3 and R4 is a synthetic lethal pair
    b. R2 and R4 is a synthetic lethal pair
    c. R3 is a single lethal
    d. R4 is a single lethal

    Ans: a, b

    Download the Escherichia coli str. K-12 substr. MG1655 model ‘iAF1260.mat’ from http://bigg.ucsd.edu/models/iAF1260. Load and analyze the model in MATLAB.

  2. What is the number of essential reactions (growth rate upon deletion results in < 5% of the wildtype growth) observed in the anaerobic iAF1260 model?

    Ans: 292

  3. Perform a knockout of the Pyruvate Dehydrogenase (PDH) reaction in the anaerobic model of iAF1260. What is the maximum acetate production flux of the knockout strain (The biomass flux should at least 90% of the wildtype under anaerobic condition)?

    Ans: 8.26 mmol/gDW/h

  4. Which of the following can help to identify a potential drug target for a bacterial disease affecting humans?
    a. A gene that does not change the biomass flux of the bacterium when knocked out.
    b. A gene that does that significantly reduces the biomass flux of the bacterium when knocked out.
    c. A bacterial protein involved in biomass production of the bacterium and having a structure different from any human proteins.
    d.A bacterial protein involved in biomass production of the bacterium and having a structure very similar to a human protein.

    Ans: b, c

  5. Consider the MATLAB code:
    [grRatio, grRateKO] = doubleGeneDeletion(model). The MATLAB command sum(grRatio<0.05) gives:

    a.The sum of the growth rates that are less than 5% of wild-type growth rate.
    b.The number of reactions for which the growth rate is 5% of wild-type growth rate.
    c.The number of gene-pair deletions for which the growth ratio is less than 0.05.
    d.The number of gene-pair deletions for which the growth rate of the deletion strain is less than 5% of the wild-type growth rate.

    Ans: c, d