A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function

Jerlström-Hultqvist, Jon; Warsi, Omar; Söderholm, Annika; Knopp, Michael; Eckhard, Ulrich; Vorontsov, Egor; Selmer, M.; Andersson, Dan I.

doi:10.1038/s41559-018-0568-5

Cited by 21 publications

(26 citation statements)

References 47 publications

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“…Depletion of S‐adenosylmethionine (SAM) by a bacteriophage SAM hydrolase caused induction of methionine biosynthesis. The upregulated MetB (cystathionine γ‐synthase) rescued an isoleucine‐dependent auxotroph by promiscuously catalyzing the reaction of IlvA (threonine dehydratase) .…”

Section: Horizontal Gene Transfer Work In Tandem With Underground Mementioning

confidence: 99%

How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation

2020

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Promiscuity is the coincidental ability of an enzyme to catalyze its native reaction and additional reactions that are not biological functions in the same active site. Promiscuity plays a central role in enzyme evolution and is thus a useful property for protein and metabolic engineering. This review examines enzyme evolution holistically, beginning with evaluating biochemical support for four enzyme evolution models. As expected, there is strong biochemical support for the subfunctionalization and innovation–amplification–divergence models, in which promiscuity is a central feature. In many cases, however, enzyme evolution is more complex than the models indicate, suggesting much is yet to be learned about selective pressures on enzyme function. A complete understanding of enzyme evolution must also explain the ability of metabolic networks to integrate new enzyme activities. Hidden within metabolic networks are underground metabolic pathways constructed from promiscuous activities. We discuss efforts to determine the diversity and pervasiveness of underground metabolism. Remarkably, several studies have discovered that some metabolic defects can be repaired via multiple underground routes. In prokaryotes, metabolic innovation is driven by connecting enzymes acquired by horizontal gene transfer (HGT) into the metabolic network. Thus, we end the review by discussing how the combination of promiscuity and HGT contribute to evolution of metabolism in prokaryotes. Future studies investigating the contribution of promiscuity to enzyme and metabolic evolution will need to integrate deeper probes into the influence of evolution on protein biophysics, enzymology, and metabolism with more complex and realistic evolutionary models. Enzymes lactate dehydrogenase (EC 1.1.1.27), malate dehydrogenase (EC 1.1.1.37), OSBS (EC 4.2.1.113), HisA (EC 5.3.1.16), TrpF, PriA (EC 5.3.1.24), R‐mandelonitrile lyase (EC 4.1.2.10), Maleylacetate reductase (EC 1.3.1.32).

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Section: Horizontal Gene Transfer Work In Tandem With Underground Mementioning

confidence: 99%

How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation

2020

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“…As an example, the Escherichia coli IlvA mutant cannot grow without supplementing Ile, but two recent reports have identified small synthetic proteins that allow to overcome this phenotype. The first report concerns a synthetic four‐helix bundle protein, whereas the second example identified an unrelated phage protein that equally allows rescue of the IlvA phenotype . Detailed transcriptomics and metabolomics studies identified the latter phage protein as a S ‐adenosylmethionine (SAM) hydrolase.…”

Section: Introductionmentioning

confidence: 78%

Increasing field strength versus advanced isotope labeling for NMR‐based fluxomics

Dinclaux

Cahoreau

Millard

et al. 2020

Magnetic Reson in Chemistry

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Nuclear magnetic resonance (NMR)‐based fluxomics seeks to measure the incorporation of isotope labels in selected metabolites to follow kinetically the synthesis of the latter. It can however equally be used to understand the biosynthetic origin of the same metabolites. We investigate here different NMR approaches to optimize such experiments in terms of resolution and time requirement. Using the isoleucine biosynthesis as an example, we explore the use of different field strengths ranging from 500 MHz to 1.1 GHz. Because of the different field dependence of chemical shift and heteronuclear J couplings, the spectra change at different field strengths. We equally explore the approach to silence the leucine/valine methyl signals through the use of a suitable deuterated precursor, thereby allowing selective observation of the Ile 13C labeling pattern. Combining both approaches, we arrive at an efficient procedure for the NMR‐based exploration of Ile biosynthesis.

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“…Half of the genomes that have been sequenced from bacterial isolates contain prophages ( 1 – 3 ). Most lysogens display changes in phenotypes, such as protection against other phage infections and additional metabolic functions ( 4 – 6 ). Despite lysogeny’s profound impacts on the structure and functioning of microbial communities, its environmental drivers remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Quantification of Lysogeny Caused by Phage Coinfections in Microbial Communities from Biophysical Principles

Luque

Silveira

2020

mSystems

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Temperate phages can associate with their bacterial host to form a lysogen, often modifying the phenotype of the host. Lysogens are dominant in the microbially dense environment of the mammalian gut. This observation contrasts with the long-standing hypothesis of lysogeny being favored at low microbial densities, such as in oligotrophic marine environments. Here, we hypothesized that phage coinfections—a well-understood molecular mechanism of lysogenization—increase at high microbial abundances. To test this hypothesis, we developed a biophysical model of coinfection for marine and gut microbiomes. The model stochastically sampled ranges of phage and bacterial concentrations, adsorption rates, lysogenic commitment times, and community diversity from each environment. In 90% of the sampled marine communities, less than 10% of the bacteria were predicted to be lysogenized via coinfection. In contrast, 25% of the sampled gut communities displayed more than 25% of lysogenization. The probability of lysogenization in the gut was a consequence of the higher densities and higher adsorption rates. These results suggest that, on average, coinfections can form two trillion lysogens in the human gut every day. In marine microbiomes, which were characterized by lower densities and phage adsorption rates, lysogeny via coinfection was still possible for communities with long lysogenic commitment times. Our study indicates that different physical factors causing coinfections can reconcile the traditional view of lysogeny at poor host growth (long commitment times) and the recent Piggyback-the-Winner framework proposing that lysogeny is favored in rich environments (high densities and adsorption rates). IMPORTANCE The association of temperate phages and bacterial hosts during lysogeny manipulates microbial dynamics from the oceans to the human gut. Lysogeny is well studied in laboratory models, but its environmental drivers remain unclear. Here, we quantified the probability of lysogenization caused by phage coinfections, a well-known trigger of lysogeny, in marine and gut microbial environments. Coinfections were quantified by developing a biophysical model that incorporated the traits of viral and bacterial communities. Lysogenization via coinfection was more frequent in highly productive environments like the gut, due to higher microbial densities and higher phage adsorption rates. At low cell densities, lysogenization occurred in bacteria with long duplication times. These results bridge the molecular understanding of lysogeny with the ecology of complex microbial communities.

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A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function

Cited by 21 publications

References 47 publications

How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation

How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation

Increasing field strength versus advanced isotope labeling for NMR‐based fluxomics

Quantification of Lysogeny Caused by Phage Coinfections in Microbial Communities from Biophysical Principles

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