#!/usr/bin/env python
# coding: utf-8

# In[3]:


from cameo import models, phenotypic_phase_plane


# In[63]:


model = models.bigg.e_coli_core.copy()


# In[64]:


model.reactions.EX_o2_e.lower_bound = 0


# In[24]:


model.reactions.EX_succ_e


# In[25]:


ppp = phenotypic_phase_plane(model,
                             variables=[model.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=model.reactions.EX_succ_e)

ppp.plot()


# In[39]:


mutant1 = model.copy()


# In[40]:


mutant1.reactions.ACKr.knock_out()
mutant1.reactions.ATPS4r.knock_out()
mutant1.reactions.ATPM.knock_out()
mutant1.reactions.FUM.knock_out()


# In[41]:


ppp = phenotypic_phase_plane(mutant1,
                             variables=[mutant1.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant1.reactions.EX_succ_e)

ppp.plot()


# In[33]:


mutant2 = model.copy()


# In[35]:


mutant2.reactions.ACALD.knock_out()
mutant2.reactions.PYK.knock_out()
mutant2.reactions.ME2.knock_out()


# In[36]:


ppp = phenotypic_phase_plane(mutant2,
                             variables=[mutant2.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant2.reactions.EX_succ_e)

ppp.plot()


# In[42]:


mutant3 = model.copy()


# In[43]:


mutant3.reactions.ACALD.knock_out()
mutant3.reactions.LDH_D.knock_out()


# In[44]:


ppp = phenotypic_phase_plane(mutant3,
                             variables=[mutant3.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant3.reactions.EX_succ_e)

ppp.plot()


# ## Excercises

# * Do any of these desigs work under aerobic conditions?
# * Can any of these designs actually be achieved with gene knockouts?

# ## Solutions

# In[67]:


### Solution 1


# In[46]:


mutant1.reactions.EX_o2_e.lower_bound = -20
ppp = phenotypic_phase_plane(mutant1,
                             variables=[mutant1.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant1.reactions.EX_succ_e)

ppp.plot()


# In[47]:


mutant2.reactions.EX_o2_e.lower_bound = -20
ppp = phenotypic_phase_plane(mutant2,
                             variables=[mutant2.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant2.reactions.EX_succ_e)

ppp.plot()


# In[49]:


mutant3.reactions.EX_o2_e.lower_bound = -20
ppp = phenotypic_phase_plane(mutant3,
                             variables=[mutant3.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant3.reactions.EX_succ_e)

ppp.plot()


# The anwer is no!

# ### Solution 2

# In[53]:


mutant3.reactions.ACALD.gene_name_reaction_rule


# In[54]:


mutant3.reactions.LDH_D.gene_name_reaction_rule


# In[58]:


for gene in mutant3.reactions.ACALD.genes:
    print(gene.name, gene.reactions)


# In[59]:


for gene in mutant3.reactions.LDH_D.genes:
    print(gene.name, gene.reactions)


# In[65]:


mutant4 = model.copy()
mutant4.reactions.ACALD.knock_out()
mutant4.reactions.LDH_D.knock_out()
mutant4.reactions.ALCD2x.knock_out()


# In[66]:


ppp = phenotypic_phase_plane(mutant4,
                             variables=[mutant4.reactions.BIOMASS_Ecoli_core_w_GAM],
                             objective=mutant4.reactions.EX_succ_e)

ppp.plot()


# The answer is yes!

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