fix/check grRules for Oxphos reactions in iSM996

[IVANDOMENZAIN]

@CarlMalina has detected inconsistencies in some grRules related to the oxidative phosphorylation and electron transport chain pathways in the iSM996 model for K. marxianus. After manual curation and a detailed revision of the genes involved in this pathway for Kmarx in KEGG and Uniprot, these are his findings:

rxnID	old grRule	new grRule
r_0175	( KLMA_20798 or KLMA_90002 or KLMA_90011 or KLMA_80159 or KLMA_80322 or KLMA_40468 or KLMA_40467 or KLMA_40511 or KLMA_60198 or KLMA_90009 or KLMA_70307 )	KLMA_90004 and KLMA_90002 and KLMA_90011 and KLMA_80159 and KLMA_40253 and KLMA_20491 and KLMA_20299 and KLMA_40066 and KLMA_40467 and KLMA_80322 and KLMA_40468
r_0176	( KLMA_90003 or KLMA_30267 )	KLMA_10723 and KLMA_90003 and KLMA_30267 and KLMA_70095 and KLMA_40479 and KLMA_50475 and KLMA_10034 and KLMA_10390 and KLMA_30208
r_0177	( KLMA_90010 or KLMA_50597 or KLMA_90009 or KLMA_90012 or KLMA_10024 or KLMA_60192 or KLMA_70216 or KLMA_20085 or KLMA_10717 or KLMA_40417 )	(KLMA_70140 and KLMA_60435 and KLMA_50237 and KLMA_30187 and KLMA_80022 and KLMA_30431 and KLMA_90010 and KLMA_10765 and KLMA_90012 and KLMA_60151 and KLMA_50351 and KLMA_30306 and KLMA_40511 and KLMA_90009 and KLMA_10227 and KLMA_60137) or (KLMA_70140 and KLMA_60435 and KLMA_50237 and KLMA_30187 and KLMA_80022 and KLMA_30431 and KLMA_90010 and KLMA_10765 and KLMA_90012 and KLMA_60151 and KLMA_50351 and KLMA_30306 and KLMA_40511 and KLMA_90009 and KLMA_10227 and KLMA_80086) or (KLMA_70140 and KLMA_60435 and KLMA_50237 and KLMA_30187 and KLMA_80022 and KLMA_30431 and KLMA_90010 and KLMA_10765 and KLMA_90012 and KLMA_60151 and KLMA_50351 and KLMA_30306 and KLMA_40511 and KLMA_90009 and KLMA_50135 and KLMA_60137) or (KLMA_70140 and KLMA_60435 and KLMA_50237 and KLMA_30187 and KLMA_80022 and KLMA_30431 and KLMA_90010 and KLMA_10765 and KLMA_90012 and KLMA_60151 and KLMA_50351 and KLMA_30306 and KLMA_40511 and KLMA_90009 and KLMA_50135 and KLMA_80086)

• r_0175 corresponds to complex IV; r_0176 to complex III; r_0177 to ATP synthase.

As it is shown in the table above, the previous grRules assume that these reactions are catalyzed by isoenzymes with a single subunit; in contrast, the suggested new grRules indicate that these reactions are catalyzed by isoenzymes, each of them consisting on enzyme complexes with several subunits.

This issue might not represent a major problem for phenotype predictions with the iSM996-GEM, however this is a major problem for its enzyme-constrained version (available here), as the enzyme requirements for these three reactions are currently under-representing the enzyme demands of the full respiratory complexes.

A repercussion of this is observed in the fact that the sigma factor its fitted to a value of 0.3 by the GECKO pipeline for eciSM996 model (evidence of this can be found in the log of the automated ecModels pipeline for this model, available here). This represents the average saturation factor for all enzymes for K. marxianus growing on conditions of unlimited glucose, which takes a value around 0.5 for all of the other organisms that have been tested with this pipeline.

[IVANDOMENZAIN]

@simas232 This is something to think about, regarding the representation of OxPhos in iSM996.

[mihai-sysbio]

It sounds to me like this problem would be better solved upstream. ecModels could then, at least for a while, use a specific branch of the source repository with a direct link to the .xml.

[IVANDOMENZAIN]

It sounds to me like this problem would be better solved upstream. ecModels could then, at least for a while, use a specific branch of the source repository with a direct link to the .xml.

I agree @mihai-sysbio, sounds like the solution should be in the original repo. To accelerate the process I can replicate this issue in the original GEM repo and create a new PR with my suggested solution (already implemented locally).