Table 5. Potential drug targets in the human pathogens S. aureus and M. tuberculosis.

Organism	Reaction Deletion Set	Subsystem	Known Drugs
S. aureus	ALATA_D	Cell wall synthesis	Vancomycin [41]
S. aureus	DHFS	Cofactor synthesis	Trimethoprim and Sulfonamides [48]
S. aureus	KAS11 or KAS12 or KAS13	Cell membrane synthesis	Small molecules [45], [46]
S. aureus	NNAM	Cofactor synthesis	Small molecules [49]
S. aureus	TECA1S or TECA2S or TECA3S or TECA4S	Cell wall synthesis	Vancomycin [41]
M. tuberculosis	CHRPL	Cell membrane synthesis	None
M. tuberculosis	FACOAL80 or FACOAL160 or FACOAL200 or FACOALPHDCA	Cell wall synthesis	Small molecules [17]
M. tuberculosis	FAS80_L or FAS100 or FAS120 or FAS140 or FAS160 or FAS180 or FAS200 or FAS240_L or FAS260 or FASPHDCA	Cell wall synthesis	Pyrazinamide [42]
M. tuberculosis	FASm220 or FASm240 or FASm260 or FASm280 or FASm300 or FASm320 or FASm340 or FASm2201 or FASm2202 or FASm2401 or FASm2402 or FASm2601 or FASm2602 or FASm2801 or FASm2802	Cell wall synthesis	Isoniazid [43], [44]
M. tuberculosis	MCBTS	Siderophore synthesis	Small molecules [50]
M. tuberculosis	PREPPACPH	Cell membrane synthesis	None
M. tuberculosis	PPTGS or PPTGS_TB1 or PPTGS_TB1 or UDCPDP	Cell wall synthesis	Ethambutol [43], [44]

We identified five unique reaction deletion sets lethal only in the iSB619 model, and seven unique reaction deletion sets lethal only in the iNJ661 model. From these, we identified 10 candidate antibiotic targets in S. aureus and 37 candidate antibiotic targets in M. tuberculosis. Antibiotics targeting some of these reactions have already been developed.