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Comparative Study
. 2002 Jun;12(6):916-29.
doi: 10.1101/gr.228002.

Comparison of the Small Molecule Metabolic Enzymes of Escherichia Coli and Saccharomyces Cerevisiae

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Free PMC article
Comparative Study

Comparison of the Small Molecule Metabolic Enzymes of Escherichia Coli and Saccharomyces Cerevisiae

Oliver Jardine et al. Genome Res. .
Free PMC article

Abstract

The comparison of the small molecule metabolism pathways in Escherichia coli and Saccharomyces cerevisiae (yeast) shows that 271 enzymes are common to both organisms. These common enzymes involve 384 gene products in E. coli and 390 in yeast, which are between one half and two thirds of the gene products of small molecule metabolism in E. coli and yeast, respectively. The arrangement and family membership of the domains that form all or part of 374 E. coli sequences and 343 yeast sequences was determined. Of these, 70% consist entirely of homologous domains, and 20% have homologous domains linked to other domains that are unique to E. coli, yeast, or both. Over two thirds of the enzymes common to the two organisms have sequence identities between 30% and 50%. The remaining groups include 13 clear cases of nonorthologous displacement. Our calculations show that at most one half to two thirds of the gene products involved in small molecule metabolism are common to E. coli and yeast. We have shown that the common core of 271 enzymes has been largely conserved since the separation of prokaryotes and eukaryotes, including modifications for regulatory purposes, such as gene fusion and changes in the number of isozymes in one of the two organisms. Only one fifth of the common enzymes have nonhomologous domains between the two organisms. Around the common core very different extensions have been made to small molecule metabolism in the two organisms.

Figures

Figure 1
Figure 1
A selection of enzymes from the KEGG Glycine, serine and threonine metabolism pathway in Escherichia coli and yeast. The domain architectures of selected enzymes from this pathway are shown as cartoons along polypeptide chains represented as black lines. Domains are assigned from structure or sequence domain databases, or identified by simple pairwise sequence similarity; these latter domains are described as belonging to ‘sequence families’. Domains can be inserted into other domains such as the Glyceraldehyde-3-phosphate dehydrogenase domain into the NAD(P)-binding Rossmann fold domains in thrA and metL. These two gene products contain the domains and catalyze the reactions of both the yeast hom3 and hom6, and are thus likely to have evolved by gene fusion. Other enzymes are identical in domain architecture, such as asd and hom2. The last enzymes on the diagram, for which there are three isozymes in E. coli and two in yeast, catalyze the same reaction, but do not have any shared domains. A nonorthologous displacement has occurred among these enzymes.
Figure 2
Figure 2
Family sizes in Escherichia coli and Saccharomyces cerevisiae common enzymes. The family sizes in number of domains is shown for E. coli on the X axis and yeast on the Y axis. Families on these axes are unique to one of the organisms, whereas most families with more than one domain are within two- to three-fold size in the two organisms.
Figure 3
Figure 3
Sequence identities between yeast and Escherichia coli common enzymes. The sequence identity for the best match with an expectation value of 0.01 or less among the gene products of yeast and E. coli common enzymes is shown. Two thirds of the matches are between 30% and 50% sequence identity.
Figure 4
Figure 4
Examples of internal duplication and domain shuffling. (a) The yeast lactoylglutathione lyase (glyoxalase I) consists of two domains of the Glyoxalase/Bleomycin resistance protein/Dihydroxybiphenyl dioxygenase family, whereas the Escherichia coli enzyme consists of one domain and is active as a homodimer. (b) The yeast glutathione synthetase contains an additional N-terminal copy of the Glutathione ATP-binding domain-like family. It is known that the E. coli enzyme is a homotetramer.
Figure 5
Figure 5
(a) This figure corresponds to the second entry in Table 8, formate dehydrogenase in Glyoxylate and dicarboxylate metabolism. This enzyme is involved in the metabolism of formate under anaerobic conditions. The reaction catalyzed is: NAD + formate → NADH + H+ + CO2. The yeast chains YPL275W and YPL276W originate from genes that are adjacent on the same yeast chromosome and make up a putative enzyme complex. The E.coli chains are known to be subunits of the formate dehydrogenase complex. (b) This figure corresponds to the fifth entry in Table 6: Ornithine decarboxylase in Arginine and proline metabolism. The reaction for this enzyme is: L-ornithine CO2 + putrescine. The Escherichia coli genes speF and speC are isozymes and so share the same structure, but differ in their regulation. SpeF is the degradative form and speC is biosynthetic. (c) This figure corresponds to entry 3 in Table 7. The enzymes shown here are from the Phenylalanine, tyrosine and tryptophan biosynthesis pathway. The Escherichia coli chain, pheA, has the functions of chorismate mutase-P and prephenate dehydratase. These functions are matched by the yeast chains aro7 (chorismate mutase) and pha2 (prephenate dehydratase). The yeast chains are not known to physically interact although they are positioned consecutively in the pathway. The discrepancy in the size (a difference of 165 residues) of the chorismate mutase domain between pheA and aro7 is interesting, suggesting it either became truncated during the fusion of the yeast chains, or possibly was expanded after the fission of the E. coli protein. The other domains involved have remained very similar in size. (d) This figure corresponds to entry 18 in Table 7. The enzymes in this example are all from folate biosynthesis. The yeast chain fol1 has the functions of dihydroneopterin aldolase, dihydro-6-hydroxymethylpterin pyrophosphokinase and dihydropteroate synthetase. YgiG is a putative kinase, folK is known as 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase, and folP is 7,8-dihydropteroate synthase. Given the structural similarity between ygiG and the first two domains of fol1 it seems likely that these two are functionally equivalent, making ygiG dihydroneopterin aldolase. The E. coli enzymes are consecutive in the pathway.
Figure 5
Figure 5
(a) This figure corresponds to the second entry in Table 8, formate dehydrogenase in Glyoxylate and dicarboxylate metabolism. This enzyme is involved in the metabolism of formate under anaerobic conditions. The reaction catalyzed is: NAD + formate → NADH + H+ + CO2. The yeast chains YPL275W and YPL276W originate from genes that are adjacent on the same yeast chromosome and make up a putative enzyme complex. The E.coli chains are known to be subunits of the formate dehydrogenase complex. (b) This figure corresponds to the fifth entry in Table 6: Ornithine decarboxylase in Arginine and proline metabolism. The reaction for this enzyme is: L-ornithine CO2 + putrescine. The Escherichia coli genes speF and speC are isozymes and so share the same structure, but differ in their regulation. SpeF is the degradative form and speC is biosynthetic. (c) This figure corresponds to entry 3 in Table 7. The enzymes shown here are from the Phenylalanine, tyrosine and tryptophan biosynthesis pathway. The Escherichia coli chain, pheA, has the functions of chorismate mutase-P and prephenate dehydratase. These functions are matched by the yeast chains aro7 (chorismate mutase) and pha2 (prephenate dehydratase). The yeast chains are not known to physically interact although they are positioned consecutively in the pathway. The discrepancy in the size (a difference of 165 residues) of the chorismate mutase domain between pheA and aro7 is interesting, suggesting it either became truncated during the fusion of the yeast chains, or possibly was expanded after the fission of the E. coli protein. The other domains involved have remained very similar in size. (d) This figure corresponds to entry 18 in Table 7. The enzymes in this example are all from folate biosynthesis. The yeast chain fol1 has the functions of dihydroneopterin aldolase, dihydro-6-hydroxymethylpterin pyrophosphokinase and dihydropteroate synthetase. YgiG is a putative kinase, folK is known as 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase, and folP is 7,8-dihydropteroate synthase. Given the structural similarity between ygiG and the first two domains of fol1 it seems likely that these two are functionally equivalent, making ygiG dihydroneopterin aldolase. The E. coli enzymes are consecutive in the pathway.
Figure 5
Figure 5
(a) This figure corresponds to the second entry in Table 8, formate dehydrogenase in Glyoxylate and dicarboxylate metabolism. This enzyme is involved in the metabolism of formate under anaerobic conditions. The reaction catalyzed is: NAD + formate → NADH + H+ + CO2. The yeast chains YPL275W and YPL276W originate from genes that are adjacent on the same yeast chromosome and make up a putative enzyme complex. The E.coli chains are known to be subunits of the formate dehydrogenase complex. (b) This figure corresponds to the fifth entry in Table 6: Ornithine decarboxylase in Arginine and proline metabolism. The reaction for this enzyme is: L-ornithine CO2 + putrescine. The Escherichia coli genes speF and speC are isozymes and so share the same structure, but differ in their regulation. SpeF is the degradative form and speC is biosynthetic. (c) This figure corresponds to entry 3 in Table 7. The enzymes shown here are from the Phenylalanine, tyrosine and tryptophan biosynthesis pathway. The Escherichia coli chain, pheA, has the functions of chorismate mutase-P and prephenate dehydratase. These functions are matched by the yeast chains aro7 (chorismate mutase) and pha2 (prephenate dehydratase). The yeast chains are not known to physically interact although they are positioned consecutively in the pathway. The discrepancy in the size (a difference of 165 residues) of the chorismate mutase domain between pheA and aro7 is interesting, suggesting it either became truncated during the fusion of the yeast chains, or possibly was expanded after the fission of the E. coli protein. The other domains involved have remained very similar in size. (d) This figure corresponds to entry 18 in Table 7. The enzymes in this example are all from folate biosynthesis. The yeast chain fol1 has the functions of dihydroneopterin aldolase, dihydro-6-hydroxymethylpterin pyrophosphokinase and dihydropteroate synthetase. YgiG is a putative kinase, folK is known as 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase, and folP is 7,8-dihydropteroate synthase. Given the structural similarity between ygiG and the first two domains of fol1 it seems likely that these two are functionally equivalent, making ygiG dihydroneopterin aldolase. The E. coli enzymes are consecutive in the pathway.
Figure 5
Figure 5
(a) This figure corresponds to the second entry in Table 8, formate dehydrogenase in Glyoxylate and dicarboxylate metabolism. This enzyme is involved in the metabolism of formate under anaerobic conditions. The reaction catalyzed is: NAD + formate → NADH + H+ + CO2. The yeast chains YPL275W and YPL276W originate from genes that are adjacent on the same yeast chromosome and make up a putative enzyme complex. The E.coli chains are known to be subunits of the formate dehydrogenase complex. (b) This figure corresponds to the fifth entry in Table 6: Ornithine decarboxylase in Arginine and proline metabolism. The reaction for this enzyme is: L-ornithine CO2 + putrescine. The Escherichia coli genes speF and speC are isozymes and so share the same structure, but differ in their regulation. SpeF is the degradative form and speC is biosynthetic. (c) This figure corresponds to entry 3 in Table 7. The enzymes shown here are from the Phenylalanine, tyrosine and tryptophan biosynthesis pathway. The Escherichia coli chain, pheA, has the functions of chorismate mutase-P and prephenate dehydratase. These functions are matched by the yeast chains aro7 (chorismate mutase) and pha2 (prephenate dehydratase). The yeast chains are not known to physically interact although they are positioned consecutively in the pathway. The discrepancy in the size (a difference of 165 residues) of the chorismate mutase domain between pheA and aro7 is interesting, suggesting it either became truncated during the fusion of the yeast chains, or possibly was expanded after the fission of the E. coli protein. The other domains involved have remained very similar in size. (d) This figure corresponds to entry 18 in Table 7. The enzymes in this example are all from folate biosynthesis. The yeast chain fol1 has the functions of dihydroneopterin aldolase, dihydro-6-hydroxymethylpterin pyrophosphokinase and dihydropteroate synthetase. YgiG is a putative kinase, folK is known as 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase, and folP is 7,8-dihydropteroate synthase. Given the structural similarity between ygiG and the first two domains of fol1 it seems likely that these two are functionally equivalent, making ygiG dihydroneopterin aldolase. The E. coli enzymes are consecutive in the pathway.

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