Subsystem: Serine-glyoxylate cycle

This subsystem's description is:

C1 assimilation proceeds via a cycle, for each constant glyoxylate regeneration is required. Glyoxylate cycle is a sourse of glyoxylate for C1 assimilation in organisms which posess Isocitrate lyase (Pseudomonas, Shewanella(?)).Most serine cycle methylotrophic bacteria lack isocitrate lyase and convert acetyl coenzyme A (acetyl-CoA) to glyoxylate via a novel pathway thought to involve butyryl-CoA and propionyl-CoA as intermediates (comes from polyxydroxybutyrate degradation). Additional Sourses of propionyl-CoA: treonine,valine, isoleucine degradation.This SS represent several pathways/cycles which were shown to be integrated in one system in Methylotrophs. It was done in an attempt to find analogous systems in other organisms.
More details regarding each block of this subsystem's network are presented below:

Glyoxylate cycle is a sourse of glyoxylate for C1 assimilation in organisms which posess Isocitrate lyase (Pseudomonas, Shewanella(?)).
Most serine cycle methylotrophic bacteria lack isocitrate lyase and convert acetyl coenzyme A (acetyl-CoA) to glyoxylate via a novel pathway thought to involve butyryl-CoA and propionyl-CoA as intermediates (comes from polyxydroxybutyrate degradation). Additional Sourses of propionyl-CoA: treonine,valine, isoleucine degradation.

Serine cycle:
Malate dehydrogenase and enolase participate also in multi-C assimilation, they are missing from Methylotrophs (?).
GlyA is found in most of organisms, its function is supplying of C1 units in the form of methylene-H4F for biosynthetic pathways, for instance, purine biosynthesis
GlyA in M. extorquens AM1, however, is specialized to methylotrophy and is not required for growth on multicarbon compounds, so an alternative source of C1 units must exist for purine biosynthesis.
Homologs of other enzymes of the serine cycle are also found in nonmethylotrophic bacteria. It therefore seems that the functionality of the serine cycle must be determined by subtle substrate specificity adjustments for the enzymes involved and by common regulation.

PNB:
Serine cycle methylotrophs accumulate PHB as a reserve material. Metabolism of PHB in M. extorquens AM1 is intimately interlinked with its C1 metabolism. The first two reactions of the PHB cycle (catalyzed by PhaA and PhaB) are also the first reactions of the GRC

Other glycine sources:
D-Threonine aldolase is an enzyme that catalyzes the cleavage of D-threonine into glycine and acetaldehyde.The aldolase reaction is reversible, and the enzyme is therefore able to produce nearly equimolar amounts of D-threonine and D-allothreonine through C-C bond formation between glycine and acetaldehyde. The enzyme also acts, in the same manner, on several other D-beta-hydroxy-alpha-amino acids, including D-beta-phenylserine, D-beta-hydroxy-alpha-aminovaleric acid, D-beta-3,4-dihydroxyphenylserine, and D-beta-3,4-methylenedioxyphenylserine.(From: Kataoka M, Ikemi M, Morikawa T, Miyoshi T, Nishi K, Wada M, Yamada H, Shimizu S.Isolation and characterization of D-threonine aldolase, a pyridoxal-5'-phosphate-dependent enzyme from Arthrobacter sp. DK-38.
Eur J Biochem. 1997 Sep 1;248(2):385-93.)

Glyoxylate regeneration:
The two enzymes participating in conversion of ethylmalonyl-CoA into isobutyryl-CoA (a putative mutase and a putative decarboxylase) are yet to be identified, and the substrate for MeaA, a putative mutase, remains unknown, as do the other enzymes involved in the conversion of beta-hydroxyisobutyryl-CoA into propionyl-CoA
Mutant analysis shows that early steps of the GRC overlap with the pathway for poly-beta-hydroxbutyrate (PHB) biosynthesis, and the late steps overlap with late steps of the TCA cycle and the serine cycle . A total of 12 genes are known that are specific to this pathway (croR, crr, pccAB, ibd2, meaABCD, mcmAB, and epm), 3 that overlap with PHB biosynthesis (phaABR), 5 that overlap with the TCA cycle (sdhABCD, fumA), and 3 that overlap with the serine cycle (mtkAB, mcl). With the exception of the four genes that are part of cluster 22 and the sdh and the pha genes, the genes for the GRC are not linked to each other or to other known methylotrophy genes. Why such an elaborate pathway is employed by many serine cycle methylotrophs instead of the classic glyoxylate shunt remains unknown. However, it may in part reflect the need for low carbon flux through the initial steps of the TCA cycle during methylotrophic growth. The GRC is viewed here as a separate metabolic module, as opposed to a part of the serine cycle due to its role not only in C1, but also in C2 metabolism in M. extorquens AM1 and possibly in other bacteria. The presence of homologs for the GRC genes (Orthologs of meaA and crr), suggesting that this pathway might be found outside of serine cycle methylotrophs in other alpha-proteobacterial genomes points towards this pathway being widespread in non-methylotrophs, and at least in Streptomyces, the pathway has been shown to be involved in C2 metabolism.

TCA:
Many of the TCA cycle enzymes are involved in C1 assimilation. Besides malate dehydrogenase, a series of the TCA cycle reactions converting succinyl-CoA into malate form a part of the GRC. Genes encoding two enzyme systems capable of converting succinyl-CoA into succinate have been identified in the genome of M. extorquens AM1: for succinyl-CoA synthase (the genes scsA and scsB are linked to mdh) and keto acid succinyl-CoA transferase (kst). In addition, cell extracts contain a succinyl-CoA hydrolase activity, but the gene responsible for this activity is unknown (Chistoserdova and Lidstrom, unpublished). Null mutations in scsB and kst caused no effect on growth of M. extorquens AM1 on C1 or multicarbon compounds (Chistoserdova and Lidstrom, unpublished). This result points toward either succinyl-CoA hydrolase being the essential enzyme for this conversion or the three systems being degenerate for this function

For more information, please check out the description and the additional notes tabs, below

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