Quantum behavior of the Duffing oscillator at the dissipative phase transition.

The non-deterministic behavior of the Duffing oscillator is classically attributed to the coexistence of two steady states in a double-well potential. However, this interpretation fails in the quantum-mechanical perspective which predicts a single unique steady state. Here, we measure the non-equilibrium dynamics of a superconducting Duffing oscillator and experimentally reconcile the classical and quantum descriptions as indicated by the Liouvillian spectral theory. We demonstrate that the two classically regarded steady states are in fact quantum metastable states. They have a remarkably long lifetime but must eventually relax into the single unique steady state allowed by quantum mechanics. By engineering their lifetime, we observe a first-order dissipative phase transition and reveal the two distinct phases by quantum state tomography. Our results reveal a smooth quantum state evolution behind a sudden dissipative phase transition and form an essential step towards understanding the intriguing phenomena in driven-dissipative systems.

Effects of dietary supplementation with histidine and ß-alanine on blood plasma metabolome of broiler chickens at different ages.

Histidine is an essential amino acid for broiler chickens and a precursor for the dipeptides carnosine and anserine, but little information is available about its metabolism in modern, fast-growing broilers. We used untargeted metabolomics to investigate the metabolic changes caused by the use of different standardized ileal digestible His:Lys ratios in broiler diets with and without ß-alanine supplementation. A total of 2204 broilers were randomly divided into 96 pens of 23 birds each. The pens were divided into 16 blocks, each containing one pen for all six feeding groups (total of 16 pens per group). These feeding groups were fed three different His:Lys ratios (0.44, 0.54, and 0.64, respectively) without and with a combination of 0.5% ß-alanine supplementation. Five randomly selected chickens of one single randomly selected pen per feeding group were slaughtered on day 35 or 54, blood was collected from the neck vessel, and plasma was used for untargeted metabolomic analysis. Here we show that up to 56.0% of all metabolites analyzed were altered by age, whereas only 1.8% of metabolites were affected by the His:Lys ratio in the diet, and 1.5% by ß-alanine supplementation. Two-factor analysis and metabolic pathway analysis showed no interaction between the His:Lys ratio and ß-alanine supplementation. The effect of the His:Lys ratio in the diet was limited to histidine metabolism with a greater change in formiminoglutamate concentration. Supplementation of ß-alanine showed changes in metabolites of several metabolic pathways; increased concentrations of 3-aminoisobutyrate showed the only direct relationship to ß-alanine metabolism. The supplementation of ß-alanine indicated few effects on histidine metabolism. These results suggest that the supplements used had limited effects or interactions on both His and ß-alanine metabolism. In contrast, the birds' age has the strongest influence on the metabolome.

Mechanical frequency control in inductively coupled electromechanical systems.

Nano-electromechanical systems implement the opto-mechanical interaction combining electromagnetic circuits and mechanical elements. We investigate an inductively coupled nano-electromechanical system, where a superconducting quantum interference device (SQUID) realizes the coupling. We show that the resonance frequency of the mechanically compliant string embedded into the SQUID loop can be controlled in two different ways: (1) the bias magnetic flux applied perpendicular to the SQUID loop, (2) the magnitude of the in-plane bias magnetic field contributing to the nano-electromechanical coupling. These findings are quantitatively explained by the inductive interaction contributing to the effective spring constant of the mechanical resonator. In addition, we observe a residual field dependent shift of the mechanical resonance frequency, which we attribute to the finite flux pinning of vortices trapped in the magnetic field biased nanostring.

Experimental quantum teleportation of propagating microwaves.

The field of quantum communication promises to provide efficient and unconditionally secure ways to exchange information, particularly, in the form of quantum states. Meanwhile, recent breakthroughs in quantum computation with superconducting circuits trigger a demand for quantum communication channels between spatially separated superconducting processors operating at microwave frequencies. In pursuit of this goal, we demonstrate the unconditional quantum teleportation of propagating coherent microwave states by exploiting two-mode squeezing and analog feedforward over a macroscopic distance of d = 0.42 m. We achieve a teleportation fidelity of F = 0.689 ± 0.004, exceeding the asymptotic no-cloning threshold. Thus, the quantum nature of the teleported states is preserved, opening the avenue toward unconditional security in microwave quantum communication.

High cooperativity in coupled microwave resonator ferrimagnetic insulator hybrids.

We report the observation of strong coupling between the exchange-coupled spins in a gallium-doped yttrium iron garnet and a superconducting coplanar microwave resonator made from Nb. The measured coupling rate of 450 MHz is proportional to the square root of the number of exchange-coupled spins and well exceeds the loss rate of 50 MHz of the spin system. This demonstrates that exchange-coupled systems are suitable for cavity quantum electrodynamics experiments, while allowing high integration densities due to their spin densities of the order of one Bohr magneton per atom. Our results furthermore show, that experiments with multiple exchange-coupled spin systems interacting via a single resonator are within reach.

Structural basis for a bispecific NADP+ and CoA binding site in an archaeal malonyl-coenzyme A reductase.

Autotrophic members of the Sulfolobales (crenarchaeota) use the 3-hydroxypropionate/4-hydroxybutyrate cycle to assimilate CO2 into cell material. The product of the initial acetyl-CoA carboxylation with CO2, malonyl-CoA, is further reduced to malonic semialdehyde by an NADPH-dependent malonyl-CoA reductase (MCR); the enzyme also catalyzes the reduction of succinyl-CoA to succinic semialdehyde onwards in the cycle. Here, we present the crystal structure of Sulfolobus tokodaii malonyl-CoA reductase in the substrate-free state and in complex with NADP(+) and CoA. Structural analysis revealed an unexpected reaction cycle in which NADP(+) and CoA successively occupy identical binding sites. Both coenzymes are pressed into an S-shaped, nearly superimposable structure imposed by a fixed and preformed binding site. The template-governed cofactor shaping implicates the same binding site for the 3'- and 2'-ribose phosphate group of CoA and NADP(+), respectively, but a different one for the common ADP part: the ß-phosphate of CoA aligns with the α-phosphate of NADP(+). Evolution from an NADP(+) to a bispecific NADP(+) and CoA binding site involves many amino acid exchanges within a complex process by which constraints of the CoA structure also influence NADP(+) binding. Based on the paralogous aspartate-ß-semialdehyde dehydrogenase structurally characterized with a covalent Cys-aspartyl adduct, a malonyl/succinyl group can be reliably modeled into MCR and discussed regarding its binding mode, the malonyl/succinyl specificity, and the catalyzed reaction. The modified polypeptide surrounding around the absent ammonium group in malonate/succinate compared with aspartate provides the structural basis for engineering a methylmalonyl-CoA reductase applied for biotechnical polyester building block synthesis.

Overexpression of alpha-ketoglutarate dehydrogenase in Yarrowia lipolytica and its effect on production of organic acids.

The yeast Yarrowia lipolytica is one of the most intensively studied "non-conventional" yeast species. Its ability to secrete various organic acids, like pyruvic (PA), citric, isocitric, and alpha-ketoglutaric (KGA) acid, in large amounts is of interest for biotechnological applications. We have studied the effect of the alpha-ketoglutarate dehydrogenase (KGDH) complex on the production process of KGA. Being well studied in Saccharomyces cerevisiae this enzyme complex consists of three subunits: alpha-ketoglutarate dehydrogenase, dihydrolipoyl transsuccinylase, and lipoamide dehydrogenase. Here we report the effect of overexpression of these subunits encoding genes and resulting increase of specific KGDH activity on organic acid production under several conditions of growth limitation and an excess of carbon source in Y. lipolytica. The constructed strain containing multiple copies of all three KGDH genes showed a reduced production of KGA and an elevated production of PA under conditions of KGA production. However, an increased activity of the KGDH complex had no influence on organic acid production under citric acid production conditions.

Methanol-based industrial biotechnology: current status and future perspectives of methylotrophic bacteria.

Methanol is one of the building blocks in the chemical industry and can be synthesized either from petrochemical or renewable resources, such as biogas. Bioprocess technology with methylotrophic bacteria is well established, as illustrated by large-scale single-cell protein production in the past. During recent years, the first genomes of methylotrophs have been sequenced and significant progress in elucidating their metabolism has been made. In addition, the tool set for genetic engineering of methylotrophic bacteria has expanded greatly and strategies to produce fine and bulk chemicals with methylotrophs have been described. This review highlights the potential of these bacteria for the development of economically competitive bioprocesses based on methanol as an alternative carbon source, bringing together biological, technical and economic considerations.

A study into the anti-microbial properties of an amino functionalised polymer using multi-parameter flow cytometry.

Fluorescent staining techniques were used to study the anti-microbial properties of aqueous suspensions of a novel, water insoluble amino functionalised polymer on three micro-organisms Pseudomonas fluorescens, Staphylococcus epidermidis and Saccharomyses cerevisiae. The mechanism of action was similar for each organism in that, after various contact times with the polymer, a progressive change in individual cell physiological state was measured using multi-parameter flow cytometry. The microbiocidal activity of this polymer may be similar to that of substances referred to as polycationic, amphipathic compounds (peptides, peptide derivatives and other polyamines).

Metabolic phenotype of phosphoglucose isomerase mutants of Corynebacterium glutamicum.

A series of experiments reported in the literature using fluxomics as an efficient functional genomics tool revealed that the L-lysine production of the Corynebacterium glutamicum strain MH20-22B correlates with the extent of intracellular NADPH supply. Some alternative metabolic engineering strategies to increase intracellular NADPH supply in the C. glutamicum strain DSM5715 were considered and finally the redirection of carbon flux through the pentose phosphate pathway with two NADPH generating enzymatic reactions was favored. Elsewhere, the construction of a phosphoglucose isomerase (Pgi) null mutant of the C. glutamicum strain DSM5715 has been described by utilizing genetic engineering as well as some aspects of its metabolic phenotype. Most interestingly, it was shown that not only could the L-lysine formation be increased by 1.7-fold but the by-product concentration for the null mutant strain was also able to be drastically reduced. In this publication we discuss this metabolic phenotype in detail and present additional data on by-product formation as well as yield considerations. Results from isotope based metabolic flux analysis in combination with considerations on NADPH metabolism clearly exclude the existence of Pgi isoenzymes in C. glutamicum strain DSM5715. The genome region containing the pgi gene was analyzed. It cannot be excluded that polar effects might have been caused by the disruption of the pgi gene and might have contributed to the observed metabolic phenotype of C. glutamicum Pgi mutants. We illustrate growth characteristics of a Pgi mutant of an industrial L-lysine production strain. A reduced growth rate and a biphasic growth behavior was observed. The importance of NADPH reoxidation for well balanced growth in Pgi mutants is discussed. Another phosphoglucose isomerase mutant of C. glutamicum has been described in literature with which an increase in L-lysine yield from 42 to 52% was observed. This finding highlights the general potential of metabolic flux redirection towards the pentose phosphate pathway, which could be used for metabolic engineering of the biotechnological synthesis of (1) aromatic amino acids and (2) chemicals whose synthesis depends on intracellular NADPH supply.

Biotechnological manufacture of lysine.

L-Lysine has been manufactured using Corynebacterium glutamicum for more than 40 years. Nowadays production exceeds 600,000 tons per year. Based on conventionally bred strains, further improvement of lysine productivity has been achieved by genetic engineering. Pyruvate carboxylase, aspartate kinase, dihydrodipicolinate synthase, homoserine dehydrogenase and the specific lysine exporter were shown to be key enzymes for lysine production and were characterized in detail. Their combined engineering led to a striking increase in lysine formation. Pathway modeling with data emerging from 13C-isotope experiments revealed a coordinated flux through pentose phosphate cycle and tricarboxylic acid cycle and intensive futile cycling between C3 compounds of glycolysis and C4 compounds of tricarboxylic acid cycle. Process economics have been optimized by developing repeated fed-batch techniques and technical continuous fermentations. In addition, on-line metabolic pathway analysis or flow cytometry may help to improve the fermentation performance. Finally, the availability of the Corynebacterium glutamicum genome sequence has a major impact on the improvement of the biotechnological manufacture of lysine. In this context, all genes of the carbon flow from sugar uptake to lysine secretion have been identified and are accessible to manipulation. The whole sequence information gives access to post genome technologies such as transcriptome analysis, investigation of the proteome and the active metabolic network. These multi-parallel working technologies will accelerate the generation of knowledge. For the first time there is a chance of understanding the overall picture of the physiological state of lysine overproduction in a technical environment.