Inorganic phosphate is a trigger factor for Microbispora sp. ATCC-PTA-5024 growth and NAI-107 production

BACKGROUND: NAI-107, produced by the actinomycete Microbispora sp. ATCC-PTA-5024, is a promising lantibiotic active against Gram-positive bacteria and currently in late preclinical-phase. Lantibiotics (lanthionine-containing antibiotics) are ribosomally synthesized and post-translationally modified peptides (RiPPs), encoded by structural genes as precursor peptides. The biosynthesis of biologically active compounds is developmentally controlled and it depends upon a variety of environmental stimuli and conditions. Inorganic phosphate (Pi) usually negatively regulates biologically-active molecule production in Actinomycetes, while it has been reported to have a positive control on lantibiotic production in Firmicutes strains. So far, no information is available concerning the Pi effect on lantibiotic biosynthesis in Actinomycetes. RESULTS: After having developed a suitable defined medium, Pi-limiting conditions were established and confirmed by quantitative analysis of polyphosphate accumulation and of expression of selected Pho regulon genes, involved in the Pi-limitation stress response. Then, the effect of Pi on Microbispora growth and NAI-107 biosynthesis was investigated in a defined medium containing increasing Pi amounts. Altogether, our analyses revealed that phosphate is necessary for growth and positively influences both growth and NAI-107 production up to a concentration of 5 mM. Higher Pi concentrations were not found to further stimulate Microbispora growth and NAI-107 production. CONCLUSION: These results, on one hand, enlarge the knowledge on Microbispora physiology, and, on the other one, could be helpful to develop a robust and economically feasible production process of NAI-107 as a drug for human use. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12934-014-0133-0) contains supplementary material, which is available to authorized users

A Two-Component regulatory system with opposite effects on glycopeptide antibiotic biosynthesis and resistance

The glycopeptide A40926, produced by the actinomycete Nonomuraea gerenzanensis, is the precursor of dalbavancin, a second-generation glycopeptide antibiotic approved for clinical use in the USA and Europe in 2014 and 2015, respectively. The final product of the biosynthetic pathway is an O-acetylated form of A40926 (acA40926). Glycopeptide biosynthesis in N. gerenzanensis is dependent upon the dbv gene cluster that encodes, in addition to the two essential positive regulators Dbv3 and Dbv4, the putative members of a two-component signal transduction system, specifically the response regulator Dbv6 and the sensor kinase Dbv22. The aim of this work was to assign a role to these two genes. Our results demonstrate that deletion of dbv22 leads to an increased antibiotic production with a concomitant reduction in glycopeptide resistance. Deletion of dbv6 results in a similar phenotype, although the effects are not as strong as in the Δdbv22 mutant. Consistently, quantitative RT-PCR analysis showed that Dbv6 and Dbv22 negatively regulate the regulatory genes (dbv3 and dbv4), as well as some dbv biosynthetic genes (dbv23 and dbv24), whereas Dbv6 and Dbv22 positively regulate transcription of the single, cluster-associated resistance gene. Finally, we demonstrate that exogenously added acA40926 and its precursor A40926 can modulate transcription of dbv genes but with an opposite extent: A40926 strongly stimulates transcription of the Dbv6/Dbv22 target genes while acA40926 has a neutral or negative effect on transcription of those genes. We propose a model in which glycopeptide biosynthesis in N. gerenzanensis is modulated through a positive feedback by the biosynthetic precursor A40926 and a negative feedback by the final product acA40926. In addition to previously reported control systems, this sophisticated control loop might help the producing strain cope with the toxicity of its own product. This work, besides leading to improved glycopeptide producing strains, enlarges our knowledge on the regulation of glycopeptide biosynthesis in actinomycetes, setting N. gerenzanensis and its two-component system Dbv6-Dbv22 apart from other glycopeptide producers

A model to explain angular distributions of J/ψJ/\psi and ψ(2S)\psi(2S) decays into ΛΛ‾\Lambda\overline{\Lambda} and Σ0Σ‾0\Sigma^0\overline{\Sigma}^0

BESIII data show a particular angular distribution for the decay of the $J/\psi$ and $\psi(2S)$ mesons into the hyperons $\Lambda\overline{\Lambda}$ and $\Sigma^0\overline{\Sigma}^0$. More in details the angular distribution of the decay $\psi(2S) \to \Sigma^0\overline{\Sigma}^0$ exhibits an opposite trend with respect to that of the other three channels: $J/\psi \to \Lambda\overline{\Lambda}$, $J/\psi \to \Sigma^0\overline{\Sigma}^0$ and $\psi(2S) \to \Lambda\overline{\Lambda}$. We define a model to explain the origin of this phenomenon.Comment: 6 pages, 7 figures, to be published in Chinese Physics

DISTO data on Kpp

The data from the DISTO Collaboration on the exclusive pp -> p K+ Lambda production acquired at T_p = 2.85 GeV have been re-analysed in order to search for a deeply bound K- pp (= X) state, to be formed in the binary process pp -> K+ X. The preliminary spectra of the DeltaM_{K+} missing-mass and of the M_{p Lambda} invariant-mass show, for large transverse-momenta of protons and kaons, a distinct broad peak with a mass M_X = 2265 +- 2 MeV/c^2 and a width Gamma_X = 118 +- 8 MeV/c^2.Comment: 8 pages, 4 figures. Talk presented at the "10th International Conference on Hypernuclear and Strange Particle Physics" (HYP-X), Tokai, Ibaraki, Japan, September 14th-18th, 2009. To appear in the proceeding

Validation of fault seal mechanisms in the Timor sea : an outcrop and subsurface perspective

When risking faulted structures, across-fault juxtaposition and or membrane seal are key issues. Generally, this work is done on a “best-guess” model. The application of SGR methods in reservoir / seal systems that have moderate Vshale values artificially increases predicted column heights. In a risking processes these large columns are discounted through other geologic risk factors. Faults in Miri, Sarawak, have been systematically mapped in outcrop in great detail to measure the strike variability of fault rocks. This work greatly helps to understand the limitation of membrane seal algorithms. To illustrate the implications to subsurface risking, a validation will be presented in which observed hydrocarbon water contacts are compared with probabilistic models for both juxtaposition and SGR. A comprehensive review of a set of fields in The Timor Sea shows that probabilistic juxtaposition models more accurately predict hydrocarbon water contacts than calibrated SGR single “best” technical models

Indication of a deeply bound compact K-pp state formed in the pp -> p Lambda K+ reaction at 2.85 GeV

We have analyzed data of the DISTO experiment on the exclusive pp -> p Lambda K+ reaction at 2.85 GeV to search for a strongly bound compact K-pp (= X) state to be formed in the pp -> K+ + X reaction. The observed spectra of the K+ missing-mass and the p Lambda invariant-mass with high transverse momenta of p and K+ revealed a broad distinct peak with a mass M_X = 2265 +- 2 (stat) +- 5 (syst) MeV/c2 and a width Gamma_X = 118 +- 8 (stat) +- 10 (syst) MeV.Comment: 4 pages, 4 figure

A genomic, transcriptomic and proteomic look at the GE2270 producer Planobispora rosea, an uncommon actinomycete

We report the genome sequence of Planobispora rosea ATCC 53733, a mycelium-forming soil-dweller belonging to one of the lesser studied genera of Actinobacteria and producing the thiopeptide GE2270. The P. rosea genome presents considerable convergence in gene organization and function with other members in the family Streptosporangiaceae, with a significant number (44%) of shared orthologs. Patterns of gene expression in P. rosea cultures during exponential and stationary phase have been analyzed using whole transcriptome shotgun sequencing and by proteome analysis. Among the differentially abundant proteins, those involved in protein metabolism are particularly represented, including the GE2270-insensitive EF-Tu. Two proteins from the pbt cluster, directing GE2270 biosynthesis, slightly increase their abundance values over time. While GE2270 production starts during the exponential phase, most pbt genes, as analyzed by qRT-PCR, are down-regulated. The exception is represented by pbtA, encoding the precursor peptide of the ribosomally synthesized GE2270, whose expression reached the highest level at the entry into stationary phase. Copyright

A Cylindrical GEM Inner Tracker for the BESIII experiment at IHEP

The Beijing Electron Spectrometer III (BESIII) is a multipurpose detector that collects data provided by the collision in the Beijing Electron Positron Collider II (BEPCII), hosted at the Institute of High Energy Physics of Beijing. Since the beginning of its operation, BESIII has collected the world largest sample of J/{\psi} and {\psi}(2s). Due to the increase of the luminosity up to its nominal value of 10^33 cm-2 s-1 and aging effect, the MDC decreases its efficiency in the first layers up to 35% with respect to the value in 2014. Since BESIII has to take data up to 2022 with the chance to continue up to 2027, the Italian collaboration proposed to replace the inner part of the MDC with three independent layers of Cylindrical triple-GEM (CGEM). The CGEM-IT project will deploy several new features and innovation with respect the other current GEM based detector: the {\mu}TPC and analog readout, with time and charge measurements will allow to reach the 130 {\mu}m spatial resolution in 1 T magnetic field requested by the BESIII collaboration. In this proceeding, an update of the status of the project will be presented, with a particular focus on the results with planar and cylindrical prototypes with test beams data. These results are beyond the state of the art for GEM technology in magnetic field

Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange