Understanding Microbial Metabolism

Downs, Diana M.

doi:10.1146/annurev.micro.60.080805.142308

Cited by 49 publications

(45 citation statements)

References 153 publications

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“…This article is cast in the spirit of the recent essay of Downs (22), which pursues the thesis that an integration of experimentally based information with bioinformatics information helps us to appreciate a metabolic network as something that is more than simply the sum of its atomistic parts. The cohesion group approach has been used to analyze Ask within the larger context of the ASK network.…”

Section: Perspectivementioning

confidence: 99%

Cohesion Group Approach for Evolutionary Analysis of Aspartokinase, an Enzyme That Feeds a Branched Network of Many Biochemical Pathways

Bonner

Xie

et al. 2009

Microbiol Mol Biol Rev

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SUMMARY Aspartokinase (Ask) exists within a variable network that supports the synthesis of 9 amino acids and a number of other important metabolites. Lysine, isoleucine, aromatic amino acids, and dipicolinate may arise from the ASK network or from alternative pathways. Ask proteins were subjected to cohesion group analysis, a methodology that sorts a given protein assemblage into groups in which evolutionary continuity is assured. Two subhomology divisions, ASKα and ASKβ, have been recognized. The ASKα subhomology division is the most ancient, being widely distributed throughout the Archaea and Eukarya and in some Bacteria. Within an indel region of about 75 amino acids near the N terminus, ASKβ sequences differ from ASKα sequences by the possession of a proposed ancient deletion. ASKβ sequences are present in most Bacteria and usually exhibit an in-frame internal translational start site that can generate a small Ask subunit that is identical to the C-terminal portion of the larger subunit of a heterodimeric unit. Particularly novel are ask genes embedded in gene contexts that imply specialization for ectoine (osmotic agent) or aromatic amino acids. The cohesion group approach is well suited for the easy recognition of relatively recent lateral gene transfer (LGT) events, and many examples of these are described. Given the current density of genome representation for Proteobacteria, it is possible to reconstruct more ancient landmark LGT events. Thus, a plausible scenario in which the three well-studied and iconic Ask homologs of Escherichia coli are not within the vertical genealogy of Gammaproteobacteria, but rather originated via LGT from a Bacteroidetes donor, is supported.

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Section: Perspectivementioning

confidence: 99%

Cohesion Group Approach for Evolutionary Analysis of Aspartokinase, an Enzyme That Feeds a Branched Network of Many Biochemical Pathways

Bonner

Xie

et al. 2009

Microbiol Mol Biol Rev

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“…Murarka, J. M. Clomburg and R. Gonzalez of fluxes we used flux balance analysis (Edwards & Palsson, 2000), a technique widely applied to the study of microbial metabolism (Downs, 2006;Romeo & Snoep, 2005;Nielsen, 2003), and referred to here as in silico MFA. To this end, simulations were conducted in different scenarios by selectively relaxing or enforcing redox (R) and ATP (A) constraints (see Table 2 and Supplementary Information for details).…”

Section: Resultsmentioning

confidence: 99%

Metabolic flux analysis of wild-type Escherichia coli and mutants deficient in pyruvate-dissimilating enzymes during the fermentative metabolism of glucuronate

2010

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The fermentative metabolism of D-glucuronic acid (glucuronate) in Escherichia coli was investigated with emphasis on the dissimilation of pyruvate via pyruvate formate-lyase (PFL) and pyruvate dehydrogenase (PDH). In silico and in vivo metabolic flux analysis (MFA) revealed that PFL and PDH share the dissimilation of pyruvate in wild-type MG1655. Surprisingly, it was found that PDH supports fermentative growth on glucuronate in the absence of PFL. The PDHdeficient strain (Pdh") exhibited a slower transition into the exponential phase and a decrease in specific rates of growth and glucuronate utilization. Moreover, a significant redistribution of metabolic fluxes was found in PDH-and PFL-deficient strains. Since no role had been proposed for PDH in the fermentative metabolism of E. coli, the metabolic differences between MG1655 and Pdh" were further investigated. An increase in the oxidative pentose phosphate pathway (ox-PPP) flux was observed in response to PDH deficiency. A comparison of the ox-PPP and PDH pathways led to the hypothesis that the role of PDH is the supply of reducing equivalents. The finding that a PDH deficiency lowers the NADH : NAD + ratio supported the proposed role of PDH. Moreover, the NADH : NAD + ratio in a strain deficient in both PDH and the ox-PPP (Pdh"Zwf") was even lower than that observed for Pdh". Strain Pdh"Zwf" also exhibited a slower transition into the exponential phase and a lower growth rate than Pdh". Finally, a transhydrogenase-deficient strain grew more slowly than wild-type but did not show the slower transition into the exponential phase characteristic of Pdh" mutants. It is proposed that PDH fulfils two metabolic functions. First, by creating the appropriate internal redox state (i.e. appropriate NADH : NAD + ratio), PDH ensures the functioning of the glucuronate utilization pathway. Secondly, the NADH generated by PDH can be converted to NADPH by the action of transhydrogenases, thus serving as biosynthetic reducing power in the synthesis of building blocks and macromolecules.

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“…In metabolic evolution, carbon dioxide respiration with hydrogen (methanogenesis and acetogenesis) was probably the first type of catabolism (Downs 2006;Falkowski et al 2008), together with several forms of respiration. However, the latter would have been limited by the availability of substrates and/or electron acceptors.…”

Section: The Energetic Basis Of Lifementioning

confidence: 99%