Rewiring Central Carbon Metabolism Ensures Increased Provision of Acetyl-CoA and NADPH Required for 3-OH-Propionic Acid Production

2020 ◽  
Vol 9 (12) ◽  
pp. 3236-3244
Author(s):  
Ning Qin ◽  
Lingyun Li ◽  
Xu Ji ◽  
Xiaowei Li ◽  
Yiming Zhang ◽  
...  
Keyword(s):  
Propionic Acid ◽  
Carbon Metabolism ◽  
Acid Production ◽  
Central Carbon Metabolism ◽  
Acetyl Coa ◽  
Central Carbon ◽  
Propionic Acid Production

scholarly journals Dynamic Metabolic Rewiring Enables Efficient Acetyl Coenzyme A Assimilation in Paracoccus denitrificans

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Katharina Kremer ◽  
Muriel C. F. van Teeseling ◽  
Lennart Schada von Borzyskowski ◽  
Iria Bernhardsgrütter ◽  
Rob J. M. van Spanning ◽  
...  
Keyword(s):  
Growth Rates ◽  
Carbon Metabolism ◽  
Paracoccus Denitrificans ◽  
High Growth ◽  
Central Carbon Metabolism ◽  
High Biomass ◽  
Acetyl Coa ◽  
Acetyl Coenzyme A ◽  
Content Type ◽  
Central Carbon

ABSTRACT During growth, microorganisms have to balance metabolic flux between energy and biosynthesis. One of the key intermediates in central carbon metabolism is acetyl coenzyme A (acetyl-CoA), which can be either oxidized in the citric acid cycle or assimilated into biomass through dedicated pathways. Two acetyl-CoA assimilation strategies in bacteria have been described so far, the ethylmalonyl-CoA pathway (EMCP) and the glyoxylate cycle (GC). Here, we show that Paracoccus denitrificans uses both strategies for acetyl-CoA assimilation during different growth stages, revealing an unexpected metabolic complexity in the organism’s central carbon metabolism. The EMCP is constitutively expressed on various substrates and leads to high biomass yields on substrates requiring acetyl-CoA assimilation, such as acetate, while the GC is specifically induced on these substrates, enabling high growth rates. Even though each acetyl-CoA assimilation strategy alone confers a distinct growth advantage, P. denitrificans recruits both to adapt to changing environmental conditions, such as a switch from succinate to acetate. Time-resolved single-cell experiments show that during this switch, expression of the EMCP and GC is highly coordinated, indicating fine-tuned genetic programming. The dynamic metabolic rewiring of acetyl-CoA assimilation is an evolutionary innovation by P. denitrificans that allows this organism to respond in a highly flexible manner to changes in the nature and availability of the carbon source to meet the physiological needs of the cell, representing a new phenomenon in central carbon metabolism. IMPORTANCE Central carbon metabolism provides organisms with energy and cellular building blocks during growth and is considered the invariable “operating system” of the cell. Here, we describe a new phenomenon in bacterial central carbon metabolism. In contrast to many other bacteria that employ only one pathway for the conversion of the central metabolite acetyl-CoA, Paracoccus denitrificans possesses two different acetyl-CoA assimilation pathways. These two pathways are dynamically recruited during different stages of growth, which allows P. denitrificans to achieve both high biomass yield and high growth rates under changing environmental conditions. Overall, this dynamic rewiring of central carbon metabolism in P. denitrificans represents a new strategy compared to those of other organisms employing only one acetyl-CoA assimilation pathway.

scholarly journals Biochemical unity revisited: microbial central carbon metabolism holds new discoveries, multi-tasking pathways, and redundancies with a reason

2020 ◽  
Vol 401 (12) ◽  
pp. 1429-1441
Author(s):  
Lennart Schada von Borzyskowski ◽  
Iria Bernhardsgrütter ◽  
Tobias J. Erb
Keyword(s):  
Carbon Metabolism ◽  
Metabolic Pathways ◽  
Central Carbon Metabolism ◽  
Genetic Redundancy ◽  
Acetyl Coa ◽  
Central Carbon ◽  
Long Time ◽  
Biochemical Research ◽  
Biochemical Diversity ◽  
Central Reaction

AbstractFor a long time, our understanding of metabolism has been dominated by the idea of biochemical unity, i.e., that the central reaction sequences in metabolism are universally conserved between all forms of life. However, biochemical research in the last decades has revealed a surprising diversity in the central carbon metabolism of different microorganisms. Here, we will embrace this biochemical diversity and explain how genetic redundancy and functional degeneracy cause the diversity observed in central metabolic pathways, such as glycolysis, autotrophic CO2 fixation, and acetyl-CoA assimilation. We conclude that this diversity is not the exception, but rather the standard in microbiology.

scholarly journals Insights into the Autotrophic CO2 Fixation Pathway of the Archaeon Ignicoccus hospitalis: Comprehensive Analysis of the Central Carbon Metabolism

2007 ◽  
Vol 189 (11) ◽  
pp. 4108-4119 ◽  
Author(s):  
Ulrike Jahn ◽  
Harald Huber ◽  
Wolfgang Eisenreich ◽  
Michael Hügler ◽  
Georg Fuchs
Keyword(s):  
Carbon Metabolism ◽  
Citrate Synthase ◽  
Central Carbon Metabolism ◽  
Comprehensive Analysis ◽  
Hyperthermophilic Archaea ◽  
Biosynthetic Pathways ◽  
Acetyl Coa ◽  
Autotrophic Co2 Fixation ◽  
Central Carbon ◽  
Ignicoccus Hospitalis

ABSTRACT Ignicoccus hospitalis is an autotrophic hyperthermophilic archaeon that serves as a host for another parasitic/symbiotic archaeon, Nanoarchaeum equitans. In this study, the biosynthetic pathways of I. hospitalis were investigated by in vitro enzymatic analyses, in vivo 13C-labeling experiments, and genomic analyses. Our results suggest the operation of a so far unknown pathway of autotrophic CO2 fixation that starts from acetyl-coenzyme A (CoA). The cyclic regeneration of acetyl-CoA, the primary CO2 acceptor molecule, has not been clarified yet. In essence, acetyl-CoA is converted into pyruvate via reductive carboxylation by pyruvate-ferredoxin oxidoreductase. Pyruvate-water dikinase converts pyruvate into phosphoenolpyruvate (PEP), which is carboxylated to oxaloacetate by PEP carboxylase. An incomplete citric acid cycle is operating: citrate is synthesized from oxaloacetate and acetyl-CoA by a (re)-specific citrate synthase, whereas a 2-oxoglutarate-oxidizing enzyme is lacking. Further investigations revealed that several special biosynthetic pathways that have recently been described for various archaea are operating. Isoleucine is synthesized via the uncommon citramalate pathway and lysine via the α-aminoadipate pathway. Gluconeogenesis is achieved via a reverse Embden-Meyerhof pathway using a novel type of fructose 1,6-bisphosphate aldolase. Pentosephosphates are formed from hexosephosphates via the suggested ribulose-monophosphate pathway, whereby formaldehyde is released from C-1 of hexose. The organism may not contain any sugar-metabolizing pathway. This comprehensive analysis of the central carbon metabolism of I. hospitalis revealed further evidence for the unexpected and unexplored diversity of metabolic pathways within the (hyperthermophilic) archaea.

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