Search NASA⌕ Search

SEARCH · Search NASA

Results for “PKS”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 145 records · Page 8

Accelerating polyketide synthase engineering for high TRY production of biofuels and bioproducts (Final Technical Report)

Polyketide synthase (PKS) enzymes have a modular, deterministic logic that holds the potential to act as a flexible chemical factory for the biological production of a huge diversity of valuable small molecule compounds. However, engineering a custom PKS to produce a specific desired product currently requires years of trial and error, for reasons that remain poorly understood. In this project, we have developed a rapid, high throughput, Design-Build-Test-Learn (DBTL) cycle for polyketide synthases (PKSs) and demonstrate its utility for production of materials precursors. The objectives are 1) to develop a rapid, high-throughput (HT) DBTL cycle for PKSs that will enable production of a large number of unnatural, organic molecules on demand at high titer, rate, and yield (TRY); 2) to demonstrate the utility of the PKS DBTL cycle to produce three molecules: one commodity chemical (caprolactam or valerolactam) and two novel materials precursors (caprolactam or valerolactam derivatives); and 3) to demonstrate the utility of the PKS DBTL cycle to increase the TRY of one molecule (caprolactam or valerolactam). In this project, we have successfully demonstrated our high throughput PKS DBTL pipeline, and have biologically produced valerolactam and several other novel nylon monomers.

60 APPLIED LIFE SCIENCES↗

Accelerating polyketide synthase engineering for high TRY production of biofuels and bioproducts (CRADA Final Report)

Polyketide synthase (PKS) enzymes have a modular, deterministic logic that holds the potential to act as a flexible chemical factory for the biological production of a huge diversity of valuable small molecule compounds. However, engineering a custom PKS to produce a specific desired product currently requires years of trial and error, for reasons that remain poorly understood. In this project, we have developed a rapid, high throughput, Design-Build-Test-Learn (DBTL) cycle for polyketide synthases (PKSs) and demonstrate its utility for production of materials precursors. The objectives are 1) to develop a rapid, high-throughput (HT) DBTL cycle for PKSs that will enable production of a large number of unnatural, organic molecules on demand at high titer, rate, and yield (TRY); 2) to demonstrate the utility of the PKS DBTL cycle to produce three molecules: one commodity chemical (caprolactam or valerolactam) and two novel materials precursors (caprolactam or valerolactam derivatives); and 3) to demonstrate the utility of the PKS DBTL cycle to increase the TRY of one molecule (caprolactam or valerolactam). In this project, we have successfully demonstrated our high throughput PKS DBTL pipeline, and have biologically produced valerolactam and several other novel nylon monomers.

09 BIOMASS FUELS↗

New very large array maps of highly core-dominated BL Lacs: Testing unified schemes

We present high dyanamic range (greater than 10 000:1) Very Large Array (VLA) maps of four highly c ore-dominated BL Lacertae Objects (PKS 0735+178, OJ 287, 1219+285, and PKS 1413+135), all of which had been reported previously as being unresolved at dynamic ranges approximately 1000-3000:1. Three of the four possess low surface brightness kpc-scale structure, with extended power levels and morphologies reasonable for FR 1 radio galaxies. One, however (PKS 1413+135), possesses no extended structure at dynamic range 9600:1. Only one of the sources exhibits aligned Very Large Array (VLA) and VLBI structures, suggesting bends on approximately 100-1000 pc size scales for the other two. As these four have extremely high core-to-extended flux ratios (f approximately 30-5000), they provide an extreme test of unified schemes. By deriving minimum constraints for the beaming angles and Lorentz factors which are required to produce the degrees of core dominance seen, we find that the three extended radio sources are consistent with being beamed FR 1 radio galaxies. PKS 1413+135 remains an anomalous BL Lac Object for several reasons.

Perlman, Eric S.↗

Chemoinformatic-Guided Engineering of Polyketide Synthases

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge is re-engineering a partially reductive PKS module to produce a saturated β-carbon through a reductive loop (RL) exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, offers a viable strategy for RL exchanges. We first introduced a set of donor RLs of diverse genetic origin and chemical substrates into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with chemical structure similarity between the substrate of the donor RLs and recipient LipPKS1, reaching a titer of 165 mg/L of short-chain fatty acids produced by the host Streptomyces albus J1074. Finally, expanding this method to larger intermediates that require bimodular communication, we introduced RLs of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

A polyketide-based biosynthetic platform for diols, amino alcohols and hydroxy acids

Medium- and branched-chain diols and amino alcohols are important industrial solvents, polymer building blocks, cosmetics and pharmaceutical ingredients, yet biosynthetically challenging to produce. Here we present an approach that uses a modular polyketide synthase (PKS) platform for the efficient production of these compounds. This platform takes advantage of a versatile loading module from the rimocidin PKS and nicotinamide adenine dinucleotide phosphate-dependent terminal thioreductases. Reduction of the terminal aldehyde with alcohol dehydrogenases enables the production of diols, oxidation enables the production of hydroxy acids and specific transaminases allow the production of various amino alcohols. Furthermore, replacement of the malonyl-coenzyme A-specific acyltransferase in the extension module with methyl- or ethylmalonyl-coenzyme A-specific acyltransferase enables the production of branched-chain diols, amino alcohols and carboxylic acids in high titres. Use of our PKS platform in Streptomyces albus demonstrated the high tunability and efficiency of the platform.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

RetroTide v1.0

RetroTide is a retrobiosynthesis software tool, designed to guide the design of biological pathways to make valuable small molecules. It takes as input a desired small molecule chemical structure, and outputs a design for a polyketide synthase enzyme (PKS) that has the closest possible chemical structure, as accessible by PKS chemistry. It is developed as a Python software library, and internally performs a search of the PKS design space, while simulating the chemicals produced by each design.

Backman, Tyler↗

Targeting the Bet-Hedging Strategy with an Inhibitor of Bacterial Efflux Capacity Enhances Antibiotic Efficiency and Ameliorates Bacterial Persistence In Vitro

Persistence is a bet-hedging strategy in bacterial populations that increases antibiotic tolerance and leads to the establishment of latent infections. In this study, we demonstrated that a synthetic non-toxic taxane-based reversal agent (tRA), developed as an inhibitor of ABC transporter systems in mammalian cancer cells, enhanced antibiotic killing of persister populations from different pathogens, including Burkholderia, Pseudomonas, Francisella, and Yersinia. Acting as an inhibitor of bacterial efflux at 100 nM, tRA99020 enhanced antibiotic efficiency and suppressed the production of natural products of Burkholderia species polyketide synthase (PKS) function. We demonstrate that the metabolites produced by PKS in response to stress by different antibiotics act as inhibitors of mammalian histone deacetylase activity and stimulate cell death. Applying a single-molecule fluorescence in situ hybridization (smFISH) assay, we analyzed on a single-cell level the activation profiles of the persistence regulating pks gene in Burkholderia thailandensis treated with tRA99020 and antibiotics. We posit that a multi-pronged approach encompassing antibiotic therapies and inhibition of efflux systems and fatty acid catabolism will be required for efficient eradication of persistent bacterial populations.

59 BASIC BIOLOGICAL SCIENCES↗

Radio sources similar to BL Lac.

Two radio sources - i.e., PKS 0727-11 and PKS 1514-24 - were monitored as part of an extensive variable source program at 2 295 MHz. The results defining the variation in radio emission of the two sources are given graphically. Only PKS 0727-11 was found to vary, and to vary in an unusual way.

Nicolson, G. D.↗

Synchrotron sources. II - Pulsars and compact extragalactic objects.

Discussion of some limitations on synchrotron models for optical pulsars and compact extragalactic objects. Using the results of a previous paper, it is shown that several existing models for the pulsar NP 0532 are inconsistent with the measured time variations and polarization of the optical emission. The possibility that the low-frequency falloffs in some extragalactic objects (PKS 2134 + 004, OQ 208, and NGC 1068) could be due to emission from particles with small pitch angles, absorption by a thermal plasma, or synchrotron self-absorption is also considered. It is found that radiation by particles with small pitch angles could explain the radio emission from PKS 2134 + 004 and OQ 208, but this process is inconsistent with the observations of NGC 1068. The absorption interpretations cannot account for the turnover in the spectrum of PKS 2134 + 004.

Epstein, R. I.↗

Spectroscopy of two BL Lacertae objects

As part of a continuing program of observations of Bl Lac objects, the IUE cameras were used to look at PKS 0548-322 and PKS 2155-304. The spectra obtained are well described by power laws with alpha approximately 0.8 in each case. For each object, one set of simultaneous X-ray data was obtained using the solid state spectrometer (SSS) on the Einstein Observatory. These data show that the power law extends from ultraviolet frequencies into the X-ray regime, although it steepens slightly for PKS 2155-304. Both objects are variable in the ultraviolet and/or X-ray; in neither case does the small spectral variability appear to correlate with the intensity variability. The overall spectrum of these objects is interpreted in light of a synchrotron self-Compton model with relativistic beaming.

Urry, C. M.↗

Evidence for accretion disks in highly polarized quasars

The results of a search for thermal components in 11 highly polarized quasars (HPQs) using UVBRI polarimetry and photometry are reported. The 2000-2500 A luminosities of the thermal components are calculated and the estimated luminosities of the broad-line region (BLR) are given in the same wavelength for comparison. The observed optical continua are modeled as a combination of polarized synchrotron emission, unpolarized emission from the BLR, and an unpolarized flat spectral component that may be optically thick thermal emission from an accretion disk. Evidence for thermal emission components is found in three HPQs: PKS 0420-014, B2 1156+295, and 3C 454.3, with marginal evidence in another two, PKS 1510-089 and PKS 2345-167.

Smith, Paul S.↗

The complex X-ray spectra of two high redshift quasars observed with ASCA

We report preliminary results of Advanced Satellite for Cosmology and Astrophysics (ASCA) observations of two high-redshift quasars (zeta approximately 3) PKS 0438-436 and PKS 2126-158. We find spectral flattening towards low energies in both sources, first found with Roentgen Satellite (ROSAT) and interpreted as being due to excess X-ray absorption. However, the ROSAT data lacked the bandpass and sensitivity to unambiguously support this interpretation. We find that for PKS 2126-158, absorption in intervening low-redshift material along the line-of-sight provides a statistically better description of the data than absorption in material intrinsic to the quasar. The redshift of the putative absorber is required to be less than a few tenths. Given the redshift constraints and the fact that absorption is not common in lower redshift quasars, this result is not easily explained by a simple model. Either the absorber may be complex or else the intrinsic X-ray spectrum may be complex, or both. Compton-reflection dominated models are ruled out but a broken power-law model provides good fits to the data without requiring excess absorption. The break energy is at approximately 6-8 keV in the quasar frame and the energy index of the soft component is required to be extremely flat. This may mean that the X-ray emission in these objects is dominated by synchrotron losses as in BL Lac objects.

Serlemitsos, Peter↗

The HI Environment of Nearby Lyman-alpha Absorbers

We present the results of a VLA and WSRT search for H I emission from the vicinity of seven nearby clouds, which were observed in Ly-alpha absorption with HST toward Mrk 335, Mrk 501, and PKS 2155-304. Around the absorbers, we searched a volume of 4O' x 40' x 1000 km/s; for one of the absorbers we probed a velocity range of only 600 km/s. The H I mass sensitivity (5 sigma) very close to the lines of sight varies from 5 x 10(exp 6) solar mass at best to 5 x 10(exp 8) solar mass at worst. We detected H I emission in the vicinity of four out of seven absorbers. The closest galaxy we find to the absorbers is a small dwarf galaxy at a projected distance of 68 h(exp -1) kpc from the sight line toward Mrk 335. This optically uncataloged galaxy has the same velocity (V = 1970 km/s) as one of the absorbers, is fainter than the SMC, and has an H I mass of only 4 x 10(exp 7) solar mass. We found a somewhat more luminous galaxy at exactly the velocity (V = 5100 km/s) of one of the absorbers toward PKS 2155-304 at a projected distance of 230 h(exp -1) kpc from the sight line. Two other, stronger absorbers toward PKS 2155-304 at V approx. 17,000 km/s appear to be associated with a loose group of three bright spiral galaxies, at projected distances of 300 to 600 h(exp -1) kpc. These results support the conclusions emerging from optical searches that most nearby Ly-alpha forest clouds trace the large-scale structures outlined by the optically luminous galaxies, although this is still based on small-number statistics. We do not find any evidence from the H I distribution or kinematics that there is a physical association between an absorber and its closest galaxy. While the absorbing clouds are at the systemic velocity of the galaxies, the H I extent of the galaxies is fairly typical, and at least an order of magnitude smaller than the projected distance to the sight line at which the absorbers are seen. On the other hand, we also do not find evidence against such a connection. In total, we detected H I emission from five galaxies, of which two were previously uncataloged and one did not have a known redshift. No H I emission was detected from the vicinity of the two absorbers, which are located in a void and a region of very low galaxy density; but the limits are somewhat less stringent than for the other sight lines. These results are similar to what has been found in optically unbiased H I surveys. Thus, presence of Ly-alpha absorbers does not significantly alter the H I detection rate in their environment.

VanGorkom, J. H.↗

Guest Investigator Studies with the Compton Gamma Ray Observatory

The cumulative all-sky survey by the Compton Gamma Ray Observatory (CGRO), composed of data acquired during the first three years of the mission, included a number of regions of very limited exposure. The most glaring deficiency in coverage was toward the region of the South Galactic Pole (SGP), which received significantly less exposure than other directions- by a factor of at least 2 to 3. Furthermore, nearly all of the SGP exposure was accumulated during the first year of the mission. Since blazars are known to be time-variable, and of unknown duty cycle, a pointing of the CCRO in that direction was considered highly desirable, and long overdue. In addition, data gathered from a pointing toward the SGP and its comparison with comprehensive data available for the North Galactic Pole would be extremely valuable to investigators studying the extragalactic diffuse emission. The reasons outlined above prompted our initiation of a Cycle 4 campaign to systematically search with EGRET and COMPTEL for gamma-ray emission from sources near the South Galactic Pole. The Cycle 4 SGP campaign consisted of tnvo 14-day observations separated in in time by approximately 10 months. The temporal separation of the observations was requested to allow a test for possible variations in the detected sources. Our primary targets were 38 FSRQs which lie within 30 degrees of the SGP, and which satisfy the basic criteria for candidate gamma-ray AGNs,flat-spectrum radio sources, many of which exhibit blazar-type properties). These targets were selected from the standard references, and from the available on-line databases (e.g., the NASA Extragalactic Database, NED), as the most promising AGN targets in the vicinity of the SGP. A 30 radius from the SGP was chosen as the boundary of our survey, since the selected targets would then fall within the most sensitive portion of the fields of view of EGRET and COMPTEL (i.e., within a 30 zenith angle), for a CGRO pointing directed exactly at the SGP. Our South Galactic Pole Survey yielded a number of exciting results. The EGRET data were analyzed using the maximum likelihood techniques to estimate the intensity, spectrum, and position of gamma-ray sources in the field of view. Our analysis revealed four sources at energies greater than 100 MeV with likelihood ratios corresponding to greater than 30 detections (Vestrand et al. 1996). One of the sources is associated with the well known gamma-ray blazar PKS 0208-512, but the other three were previously unknown. Among the new detections was PKS 2155-304 which is often considered a prototype of the x-ray selected BL Lacs. PKS 2155-304, which was also detected at hard x-ray energies by CGRO/OSSE, is one of the brightest BL Lac objects in the sky at optical through x-ray energies and has a history of rapid, strong multiwavelength variability. As such, it has been the subject of intensive, contemporaneous, multiwavelength monitoring covering radio frequencies to x-ray energies.

Vestrand, W. T.↗

Continued RXTE Observations of Three Blazars

This project continued (during Cycle 3 of the RXTE mission) weekly observations of the quasars PKS 1510-089 and 3C 454.3 and the BL Lac object OJ 287. The data were analyzed by the PI and his graduate student. In the middle of Cycle 3, the PI changed the mode of observation of 3C 454.3, based on a report from another astronomer that observations with the Rosat satellite had found a strong confusing X-ray source about 45 arcmin away. The RXTE observations, in which the flux was measured while pointing directly at 3C 454.3 and then 15' from 3C 454.3, in the direction away from the confusing source. The flux decreased considerably, and so it appears that nearly all the X-ray flux measured by RXTE comes from the confusing source rather than the quasar. OJ 287 was detected only at one epoch of the Cycle 3 observations. This corresponded to a particularly quiet period for this source, when its flux at other wavebands was also low. From the single epoch of detection, no conclusions can be drawn concerning the general nature of the X-ray emission from this object. In contrast to the other two sources, the results of the observations of PKS 1510-089, when combined with data from cycles 3 and 4, are very interesting. The RXTE (2.4-20 keV) abd 14.5 GHz University of Michigan Radio Astronomy Observatory (UMRAO) light curves through the end of RXTE Cycle 4 are shown for PKS 1510-089. Visual inspection reveals an obvious correlation between the X-ray and 14.5 GHz light curves. While this is as expected in the SSC model in a source with simultaneous mm-wave (the photons thought to be scattered to X-ray energies) and cm-wave variations, the X-ray spectrum is flat ("energy" spectral index alpha = 0.2-0.5, where F (sub v) proportional to v (sup - alpha)) compared with the mm-wave synchrotron spectrum (alpha approximately equal to 0.8). The PI is currently engaged in theoretical work to determine whether this is possible for an SSC model.

Marscher, Alan P.↗

The New BeppoSAX Observation of the Brightest X-Ray Quasar at Redshift

This grant was to support the reduction and analysis of our approved SAX observation of the high redshift (z=3.2) blazar PKS 2126-158. This is the brightest quasar at z greater than 3 and has been intensively studied in X-ray, since the first Einstein detection. In 1994 Elvis et al., discovered a strong low energy cutoff in this object, which could imply either quasar frame photoelectric absorption by a column of 0.8-2.7 x 1e22 cm-2 cold gas, or a lower column of cold gas at z=0. Subsequent ASCA observations of this object, could not definitely address this issue, nor could establish whether the curvature of the low energy portion of the spectrum was due to pure photoelectric absorption (considerably exceeding the Galactic value along the line of sight) or to an intrinsic continuum curvature. We proposed to observe PKS 2126-158 with BeppoSAX, to try to solve this puzzle (thanks to the broadband of BeppoSAX: 0.1-250 keV). PKS 2126 was observed by BeppoSAX on May 1999, with a MECS exposure of 100 ks. We have reduced and analyzed the BeppoSAX data, and compared them with a Chandra ACIS observation of the same object, taken only 6 months apart (Nov. 1999). We have recently finished to write a paper on the BeppoSAX data only, that concentrate on the properties of the X-ray absorber, which is highly requested by our SAX data, independently on the continuum model adopted. The paper (P.I.F. Fiore) will be submitted to APJ in the next few days. A second paper on the combined BeppoSAX and Chandra data, and based on the broad band spectral energy distribution of this quasar, is currently in preparation. Our main results, on the X-ray absorber, are: (a) the presence of an X-ray absorber is confirmed, indipendently on the continuum adopted (simple power law, or curved continuum); (b) if the absorber is not significantly ionized, then the BeppoSAX data do prefer a low redshift absorber; (c) if the gas is ionized, then it can be located in the quasar environment, but its metal abundances must be lower than 0.2 times solar (because of the absence of a strong FeK absorption edges that would follow at approx. 2 keV, where the MECS response is the highest).

Nicastro, Fabrizio↗

Does the Blazar Gamma-ray Spectrum Harden with Increasing Flux? - Analysis of Nine Years of EGRET Data

The Energetic Gamma Ray Experiment Telescope (EGRET) on the Compton Gamma Ray Observatory (CGRO) discovered gamma-ray emission from more than 67 blazars during its nine-year lifetime. We conducted an exhaustive search of the EGRET archives and selected all the blazars that were observed multiple times and were bright enough to enable a spectral analysis using standard powerlaw models. The sample consists of 18 flat-spectrum radio quasars (FSRQs), 6 low-frequency-peaked BL Lacs (LBLs) and 2 high-frequency-peaked BL Lacs (HBLs). We do not detect any clear pattern in'the variation of spectral index with flux. Some of the blazars do not show any statistical evidence for spectral variability. The spectrum hardens with increasing flux in a few cases. There is also evidence for a flux-hardness anticorrelation at lo\v fluxes in five blazars. The well observed blazars (3C 279,3C 273, PKS 0528-i-134, PKS 1622-297, PKS 0208- 512) do not show any overall trend in the long-term spectral dependence on flux, but the sample shows a mixture of hard and soft states. We observed spectral hysteresis at weekly timescales in all the three FSRQs for which data from flares lasting for 3 approx. 4 weeks were available. All three sources show a counterclockwise rotation despite the widely different flux profiles. Hysteresis in the spectral index vs. flux space has never been observed in FSRQs in gamma-rays at weekly timescales. itre analyze the observed spectral behavior in the context of various inverse-Compton mechanisms believed to be responsible for emission in the EGRET energy range. Our analysis uses the EGRET skymaps that were regenerated to include the changes in performance during the mission.

Nandikotkur, Giridhar↗

Producing adipic acid and related compounds using hybrid polyketide synthases

The present invention provides for a polyketide synthase (PKS) capable of synthesizing a carboxylic acid, said PKS comprising a synthetic or hybrid module. The present invention also provides for a host cell comprising the PKS and when cultured produces the carboxylic acid. In some embodiments, the carboxylic acid is adipic acid.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗