# Biossíntese de PHAmcl a partir de glicose considerando também a biossíntese de biomassa 
# considera vias ED (ciclica ou não), PPP, CK, Glioxilato, anapleróticas, transidrogenase e respiração aeróbia de coenzimas 
# 10000 XR igual a 1.000.000 g de XR ou 1 XR igual a 100 g
#
# 2017: removed VP5, put ATP and ADP as internal metabolites
# subversion: 17.2
# 17.2 : changed biomass equation once again (included water as a reactant; RNA, DNA and protein matched with KT2440 and elemental composition approximated that of LFM046)
# 17.1 : fine tuning on experimental numbers -> didn't work very well
# 17 : changed biomass equation after elemental composition analisys (found phosphorus and oxygen compositions by mass balance). Changed PHA composition to the one of chemostat 1302 (it was using 1101's). Model broke, but is very close.
# 16.6 : roll back to extreme experimental condition (P limitation, high PHA, high RQ): chemostat 1302 (can't make it work. RQ is too high even with m_ox. With PHA musch higher it works but surrealistic low XT. Lacking CO2? ADJUSTED, WORKS!)
# 16.5 : decouple m_ox from biomass formation and revert maintenance to ATP-based model (but keep it very low, not testing maintenance values yet)
# 16.4 : separate maintenance from oxidative stress based on calculations from the biomass composition (hydrogen)
# 16.3 : change maintenance / oxidative stress model
# 16.2 : add maintenance / oxidative stress model. This reaction is oxidation of acetil-coA but it is not respiration (oxygen from CO2 comes from O2 and no water is formed)
# 16.1 : experimental data from set 1101 (nitrogen)
# 16 : 15.9 copying and pasting experimental data from spreadsheet directly
# 15.9 : reverted to 15.7 after something went wrong with metatool, readded DNA
# 15.8 : changed interface to experimental data (GASEX, CINTAKE and BIOTOT reactions), added DNA
# 15.7 : replace FATS by FATI again, lower protein in biomass. Experimental data and biomass equation being generated by spreadsheet exp_data_for_oldmodel.ods (sheet exp_data_2)
# 15.6 : commented aminoacid degradation reactions (except glycine whose absence breaks the model)
# 15.5 : hypothesis: P limitation limits number of ribosomes. Lowered ribosome composition in biomass. Maximum RQ went at least up to 1.98 and there was combinatory explosion
# 15.4 : hypothesis: saturated fat. Added FATS reaction and commented FATI reaction. This only changed maximum RQ from 1.96 to 1.97.
# 15.3 : removed cofactor pools. Added 3 aminoacid degradation reactions and observed possible combinatory explosion. Added RQ restriction: maximum possible RQ is 1.96, with over 60% error in carbon intake. Added all aminoacid degradation reactions
# 15.2 : added cofactor pools. They break the model
# 15.1 : Glycine production in ATP de novo synthesis for RNA breaks model, so PGLY_D was added. Number of EM tripled. Numbers (RQ and Csource consumption) suggest that biomass has less protein and more of the rest
# 15 : all aminoacids. Once again, ATP sinks break model but if reactions all conserve ATP/ADP moiety by summing ATP synthesis reaction to ATP sinks it works (PHIS_P and FATI do that, both using the OXNAD reaction) + peptidoglycan
# 14.7 : synthesis of all aminoacids except histidine because histidine sinks 1 ATP, so RNA reactions must be included in PHIS_S or adapted first (new metabolite: ATPin)
# 14 : change biomass equation to the equation from the FBA core model to allow changes in macrocomponents, FATI reaction includes 6x ADP synthesis + corresponding OXNAD to even out ATP/ADP moiety
# 13 : tested adding back reaction VP5 (produces CO2) with and without NADP reduction (without it the charges are imbalanced)
# 12 : removed FAT in BIOTOT and tested artificial electron sinks
# 11 : made half of the krebs cycle reversible to allow oxidative and reductive linear pathways
# 10 : implemented larger fatty acid synthesis to synthesize FAT and export FAT, locked carbon source input mixture composition
# 09 : implemented HA monomer formation as sequential spiral, locked PHA composition and locked PHA to XR composition
# 08 : added fructose intake, reordered external metabolites, turned O into O2 and improved P:O ratio, fixed reversibility of transhydrogenases
# 07 : added UDH and C12d5
#
# FATS : 7 C10 + 6 C12 + 9 C12g + 61 C16g + 17 C18g + 50 DHP + 13 ATP + 38 NADPH + 13.2 NADH + 18.6 O2 + 18 SER + 50 CTP + 12 GLN + 12 ASP = 1 FAT_KT2440_2013 + 13 ADP + 38 NADP + 13.2 NAD + 12 CO2 + G6P + 6 GLY + 12 GLU + 12 Fum + 12 GLX + 36 NH3
# F18g : C16g + 1 AcCoA + 2 NADPH + 1 ATP = C18g + 1 CoASH + 2 NADP + 1 ADP
# F18g2 : C18d11g + NADPH = C18g + NADP


-ENZREV
EMP2A EMP2B EMP4 EMP5 EMP6 EMP7 EMP8 EMP9 VP6 VP7 VP8 VP9 VP10 CK5 CK6 CK7 CK8 


PGLU_SD PGLN_SD PASP_SD PALA_SD PFMET_SD

-ENZIRREV
BIOTOT CINTAKE BIO MAIN OXSTRESS NINTAKE
EMP1A EMP1B ED1 ED2 EMP10 CPD VP1 CK1 CK2 CK3 CK4 CGLX1 CGLX2 GLN3 AD1 AD2 OXFAD OXNAD TRANS UDH 
F04 F06 F08 F10 F12 F12d5 F12g FPHA F14 F14g F16g F16d9g F16g2 F18d11g FLPS FPGLYC FCARD FPETAM FATI
PPROT PSER_S PASN_S PARG_S PPRO_S PGLY_S PILE_S PCYS_S PLEU_S PLYS_S PMET_S PPHE_S PTHR_S PTYR_S PTRP_S PVAL_S PHIS_S
PGLY_D
RATP RUTP RCTP RGTP RNA_S RIBO_S
PEPGLY_S
CARB_S
DDATP DDCTP DDGTP DTTP DNA_S
GASEX

-METINT
Gliex Fruex ADP ATP G6P F1P KDPG2 NADP NADPH PG6 PIR G3P BPG13 PG3 PG2 PEP AcCoA Rbl5P Rb5P X5P S7P E4P F6P DHP F16P OAA Cit KG2 IsoCit SucCoA Suc Fum Mal FAD FADH2 NAD NADH CoASH GLX
XR PROT
C04 C06 C08 C10 C12 C12d5 PHA C12g C14 C14g C16g C16d9g C18d11g FAT_KT2440_2013 LPS CARD PGLYC PETAM
ALA ARG ASN ASP CYS FMET GLN GLU GLY HIS ILE LEU LYS MET PHE PRO SER THR TRP TYR VAL
RNAATP UTP CTP GTP RNA RIBO
PEPGLY_KT_2011
CARB
DATP DCTP DGTP TTP DNA
O2 CO2 NH3
m_all

-METEXT
Csource Gases XT Nsource m_ox

-CAT
NINTAKE : Nsource = 0.05 NH3
OXSTRESS : NADPH = NADP + 1 m_ox
MAIN : 1 ATP = 1 ADP + 1 m_all
CINTAKE : 1 Csource = 3.663 Gliex 
BIOTOT : 1 XR + 0.73 PHA + 16 m_all = 1 XT
FPHA : 26 C06 + 210 C08 + 616 C10 + 95 C12d5 + 52 C12 = 1000 PHA
BIO : 6.8931 DNA + 5.1698 PROT + 0.0345 LPS + 0.0022 CARD + 0.008 PGLYC + 0.0334 PETAM + 0.005 AcCoA + 0.0001 CARB + 0.2378 PEPGLY_KT_2011 + 6.8931 RIBO = 100 XR + 0.005 CoASH
GASEX : 11 CO2 = 5.9 O2 + Gases

EMP1B : Fruex + ATP = F1P + ADP
EMP2B : F1P + ATP = F16P + ADP
EMP1A : Gliex + ATP = G6P + ADP
EMP2A : G6P = F6P
ED1 : PG6 = KDPG2
ED2 : KDPG2 = PIR + G3P
EMP4 : F16P = G3P + DHP
EMP5 : DHP = G3P
EMP6 : G3P + NAD = BPG13 + NADH
EMP7 : BPG13 + ADP = PG3 + ATP
EMP8 : PG3 = PG2
EMP9 : PG2 = PEP
EMP10 : PEP + ADP = PIR + ATP
CPD : PIR + NAD + CoASH = AcCoA + NADH + CO2
VP1 : G6P + NADP = PG6 + NADPH
VP6 : Rbl5P = Rb5P
VP7 : Rbl5P = X5P
VP8 : Rb5P + X5P = S7P + G3P
VP9 : G3P + S7P = E4P + F6P
VP10 : X5P + E4P = F6P + G3P
CK1 : OAA + AcCoA = Cit + CoASH
CK2 : Cit = IsoCit
CK3 : IsoCit + NADP = KG2 + NADPH + CO2
CK4 : KG2 + NAD + CoASH = SucCoA + NADH + CO2
CK5 : SucCoA + ADP = Suc + ATP + CoASH
CK6 : Suc + FAD = Fum + FADH2
CK7 : Fum = Mal
CK8 : Mal + NAD = OAA + NADH
CGLX1 : IsoCit = GLX + Suc
CGLX2 : GLX + AcCoA = Mal + CoASH
GLN3 : F16P = F6P
AD1 : PIR + CO2 + ATP = OAA + ADP
AD2 : OAA + ATP = PEP + ADP + CO2
OXFAD : FADH2 + 1.5 ADP + 0.5 O2 = FAD + 1.5 ATP
OXNAD : NADH + 2.5 ADP + 0.5 O2 = NAD + 2.5 ATP
TRANS : NADH + ATP + NADP = NADPH + NAD + ADP
UDH : NAD + NADPH = NADP + NADH

F04 : 2 AcCoA + 1 NADPH + 1 ATP = C04 + 2 CoASH + 1 NADP + 1 ADP
F06 : C04 + 1 AcCoA + 2 NADPH + 1 ATP = C06 + 1 CoASH + 2 NADP + 1 ADP
F08 : C06 + 1 AcCoA + 2 NADPH + 1 ATP = C08 + 1 CoASH + 2 NADP + 1 ADP
F10 : C08 + 1 AcCoA + 2 NADPH + 1 ATP = C10 + 1 CoASH + 2 NADP + 1 ADP
F12 : C10 + 1 AcCoA + 2 NADPH + 1 ATP = C12 + 1 CoASH + 2 NADP + 1 ADP
F12d5 : C10 + 1 AcCoA + 1 NADPH + 1 ATP = C12d5 + 1 CoASH + 1 NADP + 1 ADP
F12g : C12 + NADPH = C12g + NADP
F14 : C12g + 1 AcCoA + 1 NADPH + 1 ATP = C14 + 1 CoASH + 1 NADP + 1 ADP
F14g : C14 + NADPH = C14g + NADP
F16g : C14g + 1 AcCoA + 2 NADPH + 1 ATP = C16g + 1 CoASH + 2 NADP + 1 ADP
F16d9g : C12d5 + 2 AcCoA + 5 NADPH + 2 ATP = C16d9g + 2 CoASH + 5 NADP + 2 ADP
F16g2 : C16d9g + NADPH = C16g + NADP
F18d11g : C16d9g + 1 AcCoA + 2 NADPH + 1 ATP = C18d11g + 1 CoASH + 2 NADP + 1 ADP

FATI : 7 C10 + 6 C12 + 9 C12g + 29 C16g + 32 C16d9g + 17 C18d11g + 50 DHP + 13 ATP + 38 NADPH + 13.2 NADH + 18.6 O2 + 18 SER + 50 CTP + 12 GLN + 12 ASP = 1 FAT_KT2440_2013 + 13 ADP + 38 NADP + 13.2 NAD + 12 CO2 + G6P + 6 GLY + 12 GLU + 12 Fum + 12 GLX + 36 NH3

FLPS : 4 C14 + C12g + C14g + 33 ATP + 4 NADPH + 3 Rb5P + 8 G6P + 2 F6P + 4 S7P + 3 PEP = 1 LPS + 33 ADP + 4 NADP
FPGLYC : 1 FAT_KT2440_2013 + 50 NADPH + 100 ATP + 50 DHP = 1 PGLYC + 50 NADP + 100 ADP + 50 CTP
FCARD : 1 FAT_KT2440_2013 + 100 ATP + 1 PGLYC = 1 CARD + 100 ADP + 50 CTP
FPETAM : 1 FAT_KT2440_2013 + 50 SER + 100 ATP = 1 PETAM + 50 CO2 + 100 ADP + 50 CTP

PPROT : 0.5137 ALA + 0.000223 FMET + 0.2958 ARG + 0.2411 ASN + 0.2411 ASP + 0.09158 CYS + 0.2632 GLN + 0.2632 GLU + 0.6126 GLY + 0.09474 HIS + 0.2905 ILE + 0.4505 LEU + 0.3432 LYS + 0.1537 MET + 0.1759 PHE + 0.2211 PRO + 0.2158 SER + 0.2537 THR + 0.05684 TRP + 0.1379 TYR + 0.4232 VAL = 1 PROT
PGLU_SD : KG2 + NADPH + NH3 = GLU + NADP
PGLN_SD : 2 GLU + NADP = GLN + NADPH + KG2
PSER_S : GLU + PG3 + NAD = SER + KG2 + NADH
PASP_SD : ASP + KG2 = OAA + GLU
PALA_SD : PIR + NADPH + NH3 = ALA + NADP
PASN_S : 2 ATP + ASP + GLN = 2 ADP + ASN + GLU
PARG_S : ASP + 4 ATP + 2 GLU + NADPH + NH3 + CO2 = ARG + 4 ADP + KG2 + NADP + Fum
PPRO_S : GLU + 2 NADPH = PRO + 2 NADP
PGLY_S : SER + NADP + 0.5 O2 = GLY + NADPH + CO2
PCYS_S : 4 ATP + FADH2 + 3 NADPH + SER = 4 ADP + CYS + FAD + 3 NADP
PMET_S : CYS + SER + ASP + 3 ATP + 3 NADPH = MET + GLY + PIR + 3 ADP + 3 NADP + NH3
PPHE_S : GLU + E4P + 2 PEP + ATP + NADPH = PHE + KG2 + ADP + NADP + CO2
PTYR_S : E4P + 2 PEP + ATP + GLU = ADP + CO2 + KG2 + TYR
PTRP_S : SER + E4P + Rb5P + 2 PEP + 3 ATP + NADPH + GLN = TRP + PIR + G3P + 3 ADP + NADP + GLU + CO2
PVAL_S : GLU + 2 PIR + NADPH = VAL + KG2 + NADP + CO2
PTHR_S : ASP + 2 NADPH + 2 ATP = THR + 2 NADP + 2 ADP
PILE_S : THR + NADPH + GLU + PIR = ILE + NADP + NH3 + KG2 + CO2
PLEU_S : VAL + AcCoA + NAD = LEU + CoASH + NADH + CO2
PLYS_S : ASP + ATP + 2 NADPH + PIR + SucCoA + GLU = LYS + ADP + 2 NADP + Suc + CoASH + KG2 + CO2
PHIS_S : 3 GLN + 3 SER + 2 ATP + 0.8 NAD + 3 NADP + 2.1 O2 + 2 ASP + 1 Rb5P = 2 CO2 + 0.8 NADH + 1 HIS + 2 GLY + 2 ADP + 3 NADPH + 1 KG2 + 4 NH3 + 1 GLX + 2 GLU + 2 Fum
PFMET_SD : FMET + NADP = MET + CO2 + NADPH

PGLY_D : 0.5 O2 + GLY = NH3 + GLX

RATP : Rb5P + 2 SER + 2 ASP + 2 NADP + 3.2 NADH + 2 GLN + CO2 + 1.6 O2 = 1 RNAATP + 2 NADPH + 3.2 NAD + 2 GLU + GLY + 2 Fum
RUTP : Rb5P + 6 ATP + GLN + ASP + 0.5 O2 = UTP + 6 ADP + GLU
RCTP : UTP + ATP + GLN = CTP + ADP + GLU
RGTP : Rb5P + 11 ATP + 3 GLN + 2 NADP + NAD + ASP + CO2 + 2 SER = GTP + 11 ADP + 3 GLU + 2 NADPH + NADH + Fum + GLY

RNA_S : 0.174 RNAATP + 0.1335 CTP + 0.2151 GTP + 0.1441 UTP = RNA
RIBO_S : 0.4 PROT + RNA = RIBO

PEPGLY_S : 1 ASP + 9 ATP + 3 NADPH + PEP + 2 AcCoA + SucCoA + PIR + 3 ALA + 2 G6P + 2 GLN = PEPGLY_KT_2011 + 9 ADP + 3 NADP + 3 CoASH + Suc + KG2

CARB_S : G6P + ATP = CARB + ADP

DDATP : RNAATP + NADPH = DATP + NADP
DDCTP : CTP + NADPH = DCTP + NADP
DDGTP : GTP + NADPH = DGTP + NADP
DTTP : CTP + 2 ATP + SER + 2 NADPH = TTP + 2 ADP + GLY + 2 NADP + NH3
DNA_S : 0.02617 DATP + 0.02702 DCTP + 0.02617 TTP + 0.02702 DGTP = DNA