Elemental Economy

Merchant, Sabeeha; Helmann, John D.

doi:10.1016/b978-0-12-398264-3.00002-4

Cited by 180 publications

(74 citation statements)

References 494 publications

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“…Indeed, many central bioenergetic and biogeochemical processes on Earth, including respiration, photosynthesis, and nitrogen fixation, are absolutely dependent on metal ion co-factors 1 . Here, we focus on those processes that allow bacteria to maintain metal homeostasis, in particular, of three most important metals for metabolism — zinc, iron and manganese.…”

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confidence: 99%

Metal homeostasis and resistance in bacteria

2017

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Metal ions are essential for many reactions, however, metal excess can be toxic. In bacteria, metal limitation activates pathways for import and mobilization of metals, whereas metal excess induces efflux and storage. In this Review, we highlight recent insights into metal homeostasis, including protein- and RNA-based sensors that interact directly with metals or metal-containing cofactors. The resulting transcriptional response to metal stress is deployed in a stepwise manner, and is reinforced by post-transcriptional regulatory systems. Metal limitation and intoxication by the host is an evolutionarily ancient strategy to limit bacterial growth. The details of the resulting growth restriction are beginning to be understood, and appear to be organism-specific.

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confidence: 99%

Metal homeostasis and resistance in bacteria

2017

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“…Zn is not redox active under normal physiological conditions, but serves as an electrophilic catalyst (Lewis acid) in numerous enzymes and as a scaffold for organizing protein domains 14 . Our studies have shown a Zn requirement for in vitro growth of Y. pestis .…”

Section: In Vitro and In Silico Analysis Of Transition Metal Transpormentioning

confidence: 99%

“…While copper is required for growth in a number of bacteria and serves as a cofactor in cellular processes; 14 excess Cu is toxic. Relatively few Cu import systems have been identified – with P-type ATPases in Pseudomonas aeruginosa and Listeria monocytogenes being two exceptions.…”

Section: In Vitro and In Silico Analysis Of Transition Metal Transpormentioning

confidence: 99%

The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis

2015

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Yersinia pestis, the causative agent of bubonic, septicemic and pneumonic plague, encodes a multitude of Fe transport systems. Some of these are defective due to frameshift or IS element insertions, while others are functional in vitro but have no established role in causing infections. Indeed only 3 Fe transporters (Ybt, Yfe and Feo) have been shown to be important in at least one form of plague. The yersiniabactin (Ybt) system is essential in the early dermal/lymphatic stages of bubonic plague, irrelevant in the septicemic stage, and critical in pneumonic plague. Two Mn transporters have been characterized (Yfe and MntH). These two systems play a role in bubonic plague but the double yfe mntH mutant is fully virulent in a mouse model of pneumonic plague. The same in vivo phenotype occurs with a mutant lacking two (Yfe and Feo) of four ferrous transporters. A role for the Ybt siderophore in Zn acquisition has been revealed. Ybt-dependent Zn acquisition uses a transport system completely independent of the Fe-Ybt uptake system. Together Ybt components and ZnuABC play a critical role in Zn acquisition in vivo. Single mutants in either system retain high virulence in a mouse model of septicemic plague while the double mutant is completely avirulent.

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“…This indicates that the RCM Bmas variant already shows slight growth inhibition, resulting in maximal biomass values of only 12 g liter Ϫ1 and deduced cellular nitrogen values of about 8%. Obviously, in both recombinant strains the ability to adapt to nitrogen limitation by PHB production and recycling of cellular components, e.g., by ribophagy (36), is substantially decreased.…”

Section: Discussionmentioning

confidence: 99%

Production of 2-Hydroxyisobutyric Acid from Methanol by Methylobacterium extorquens AM1 Expressing ( R )-3-Hydroxybutyryl Coenzyme A-Isomerizing Enzymes

Rohde

Tischer

Harms

et al. 2017

Appl Environ Microbiol

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The biotechnological production of the methyl methacrylate precursor 2-hydroxyisobutyric acid (2-HIBA) via bacterial poly-3-hydroxybutyrate (PHB) overflow metabolism requires suitable (R)-3-hydroxybutyryl coenzyme A (CoA)-specific coenzyme B 12 -dependent mutases (RCM). Here, we characterized a predicted mutase from Bacillus massiliosenegalensis JC6 as a mesophilic RCM closely related to the thermophilic enzyme previously identified in Kyrpidia tusciae DSM 2912 (M.-T. Weichler et al., Appl Environ Microbiol 81:4564 -4572, 2015, https://doi.org/10.1128/ AEM.00716-15). Using both RCM variants, 2-HIBA production from methanol was studied in fed-batch bioreactor experiments with recombinant Methylobacterium extorquens AM1. After complete nitrogen consumption, the concomitant formation of PHB and 2-HIBA was achieved, indicating that both sets of RCM genes were successfully expressed. However, although identical vector systems and incubation conditions were chosen, the metabolic activity of the variant bearing the RCM genes from strain DSM 2912 was severely inhibited, likely due to the negative effects caused by heterologous expression. In contrast, the biomass yield of the variant expressing the JC6 genes was close to the wild-type performance, and 2-HIBA titers of 2.1 g liter Ϫ1 could be demonstrated. In this case, up to 24% of the substrate channeled into overflow metabolism was converted to the mutase product, and maximal combined 2-HIBA plus PHB yields from methanol of 0.11 g g Ϫ1 were achieved. Reverse transcription-quantitative PCR analysis revealed that metabolic genes, such as methanol dehydrogenase and acetoacetyl-CoA reductase genes, are strongly downregulated after exponential growth, which currently prevents a prolonged overflow phase, thus preventing higher product yields with strain AM1.IMPORTANCE In this study, we genetically modified a methylotrophic bacterium in order to channel intermediates of its overflow metabolism to the C 4 carboxylic acid 2-hydroxyisobutyric acid, a precursor of acrylic glass. This has implications for biotechnology, as it shows that reduced C 1 substrates, such as methanol and formic acid, can be alternative feedstocks for producing today's commodities. We found that product titers and yields depend more on host physiology than on the activity of the introduced heterologous function modifying the overflow metabolism. In addition, we show that the fitness of recombinant strains substantially varies when they express orthologous genes from different origins. Further studies are needed to extend the overflow production phase in methylotrophic microorganisms for the implementation of biotechnological processes.KEYWORDS acyl-CoA mutase, bulk chemicals, fed-batch bioreactor, overflow metabolism, polyhydroxybutyrate

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Elemental Economy

Cited by 180 publications

References 494 publications

Metal homeostasis and resistance in bacteria

Metal homeostasis and resistance in bacteria

The role of transition metal transporters for iron, zinc, manganese, and copper in the pathogenesis of Yersinia pestis

Production of 2-Hydroxyisobutyric Acid from Methanol by Methylobacterium extorquens AM1 Expressing ( R )-3-Hydroxybutyryl Coenzyme A-Isomerizing Enzymes

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