Proposing Genes for Gap Reactions in Metabolic Pathways

A metabolic model is a map of the biochemical reactions that take place in an organism. These reactions are catalyzed by enzymes, which are encoded by genes in the organism’s genome. However, there are reactions that are known to exist and needed to complete the metabolic model, but are not associated with any genes. These are called “gap reactions”. Our goal is to find the genes that encode the enzymes that catalyze these gap reactions. We have researched two approaches: a knowledge-driven approach that focuses on finding a small set of good candidates, and a data-driven approach that focuses on scoring all candidates to rank their plausibility. Identifying the genes that are associated with gap reactions produces better predictive models and directs laboratory experimentation

HD 20329b: An ultra-short-period planet around a solar-type star found by TESS

We used TESS light curves and HARPS-N spectrograph radial velocity measurements to establish the physical properties of the transiting exoplanet candidate found around the star HD 20329 (TOI-4524). We performed a joint fit of the light curves and radial velocity time series to measure the mass, radius, and orbital parameters of the candidate. We confirm and characterize HD 20329b, an ultra-short-period (USP) planet transiting a solar-type star. The host star (HD 20329, $V = 8.74$ mag, $J = 7.5$ mag) is characterized by its G5 spectral type with $\mathrm{M}_\star= 0.90 \pm 0.05$ M$_\odot$, $\mathrm{R}_\star = 1.13 \pm 0.02$ R$_\odot$, and $\mathrm{T}_{\mathrm{eff}} = 5596 \pm 50$ K; it is located at a distance $d= 63.68 \pm 0.29$ pc. By jointly fitting the available TESS transit light curves and follow-up radial velocity measurements, we find an orbital period of $0.9261 \pm (0.5\times 10^{-4})$ days, a planetary radius of $1.72 \pm 0.07$ $\mathrm{R}_\oplus$, and a mass of $7.42 \pm 1.09$ $\mathrm{M}_\oplus$, implying a mean density of $\rho_\mathrm{p} = 8.06 \pm 1.53$ g cm$^{-3}$. HD 20329b joins the $\sim$30 currently known USP planets with radius and Doppler mass measurements.Comment: Accepted for publication in A&A, 26 page

A low-eccentricity migration pathway for a 13-h-period Earth analogue in a four-planet system

It is commonly accepted that exoplanets with orbital periods shorter than one day, also known as ultra-short-period (USP) planets, formed further out within their natal protoplanetary disks before migrating to their current-day orbits via dynamical interactions. One of the most accepted theories suggests a violent scenario involving high-eccentricity migration followed by tidal circularization. Here we present the discovery of a four-planet system orbiting the bright (V = 10.5) K6 dwarf star TOI-500. The innermost planet is a transiting, Earth-sized USP planet with an orbital period of ~13 hours, a mass of 1.42 ± 0.18 M⊕, a radius of 1.166−0.058+0.061R⊕ and a mean density of 4.89−0.88+1.03gcm−3. Via Doppler spectroscopy, we discovered that the system hosts 3 outer planets on nearly circular orbits with periods of 6.6, 26.2 and 61.3 days and minimum masses of 5.03 ± 0.41 M⊕, 33.12 ± 0.88 M⊕ and 15.05−1.11+1.12M⊕, respectively. The presence of both a USP planet and a low-mass object on a 6.6-day orbit indicates that the architecture of this system can be explained via a scenario in which the planets started on low-eccentricity orbits then moved inwards through a quasi-static secular migration. Our numerical simulations show that this migration channel can bring TOI-500 b to its current location in 2 Gyr, starting from an initial orbit of 0.02 au. TOI-500 is the first four-planet system known to host a USP Earth analogue whose current architecture can be explained via a non-violent migration scenario

TOI-2196 b : Rare planet in the hot Neptune desert transiting a G-type star

Funding: C.M.P., M.F., I.G., and J.K. gratefully acknowledge the support of the Swedish National Space Agency (DNR 65/19, 174/18, 177/19, 2020-00104). L.M.S and D.G. gratefully acknowledge financial support from the CRT foundation under Grant No. 2018.2323 “Gaseous or rocky? Unveiling the nature of small worlds”. P.K. acknowledges support from grant LTT-20015. E.G. acknowledge the support of the Thüringer Ministerium für Wirtschaft, Wissenschaft und Digitale Gesellschaft. J.S.J. gratefully acknowledges support by FONDECYT grant 1201371 and from the ANID BASAL projects ACE210002 and FB210003. H.J.D. acknowledges support from the Spanish Research Agency of the Ministry of Science and Innovation (AEI-MICINN) under grant PID2019-107061GBC66, DOI: 10.13039/501100011033. D.D. acknowledges support from the TESS Guest Investigator Program grants 80NSSC21K0108 and 80NSSC22K0185. M.E. acknowledges the support of the DFG priority program SPP 1992 "Exploring the Diversity of Extrasolar Planets" (HA 3279/12-1). K.W.F.L. was supported by Deutsche Forschungsgemeinschaft grants RA714/14-1 within the DFG Schwerpunkt SPP 1992, Exploring the Diversity of Extrasolar Planets. N.N. acknowledges support from JSPS KAKENHI Grant Number JP18H05439, JST CREST Grant Number JPMJCR1761. M.S.I.P. is funded by NSF.The hot Neptune desert is a region hosting a small number of short-period Neptunes in the radius-instellation diagram. Highly irradiated planets are usually either small (R ≲ 2 R⊕) and rocky or they are gas giants with radii of ≳1 RJ. Here, we report on the intermediate-sized planet TOI-2196 b (TIC 372172128.01) on a 1.2 day orbit around a G-type star (V = 12.0, [Fe/H] = 0.14 dex) discovered by the Transiting Exoplanet Survey Satellite in sector 27. We collected 41 radial velocity measurements with the HARPS spectrograph to confirm the planetary nature of the transit signal and to determine the mass. The radius of TOI-2196 b is 3.51 ± 0.15 R⊕, which, combined with the mass of 26.0 ± 1.3 M⊕, results in a bulk density of 3.31−0.43+0.51 g cm−3. Hence, the radius implies that this planet is a sub-Neptune, although the density is twice than that of Neptune. A significant trend in the HARPS radial velocity measurements points to the presence of a distant companion with a lower limit on the period and mass of 220 days and 0.65 MJ, respectively, assuming zero eccentricity. The short period of planet b implies a high equilibrium temperature of 1860 ± 20 K, for zero albedo and isotropic emission. This places the planet in the hot Neptune desert, joining a group of very few planets in this parameter space discovered in recent years. These planets suggest that the hot Neptune desert may be divided in two parts for planets with equilibrium temperatures of ≳1800 K: a hot sub-Neptune desert devoid of planets with radii of ≈ 1.8−3 R⊕ and a sub-Jovian desert for radii of ≈5−12 R⊕. More planets in this parameter space are needed to further investigate this finding. Planetary interior structure models of TOI-2196 b are consistent with a H/He atmosphere mass fraction between 0.4% and 3%, with a mean value of 0.7% on top of a rocky interior. We estimated the amount of mass this planet might have lost at a young age and we find that while the mass loss could have been significant, the planet had not changed in terms of character: it was born as a small volatile-rich planet and it remains one at present.Publisher PDFPeer reviewe

HD 20329b: An ultra-short-period planet around a solar-type star found by TESS

We used TESS light curves and HARPS-N spectrograph radial velocity measurements to establish the physical properties of the transiting exoplanet candidate found around the star HD 20329 (TOI-4524). We performed a joint fit of the light curves and radial velocity time series to measure the mass, radius, and orbital parameters of the candidate. We confirm and characterize HD 20329b, an ultra-short-period (USP) planet transiting a solar-type star. The host star (HD 20329, V = 8.74 mag, J = 7.5 mag) is characterized by its G5 spectral type with M_star= 0.90 ± 0.05 M_sun, R_star = 1.13 ± 0.02 R_sun, and T_eff = 5596 ± 50 K; it is located at a distance d= 63.68 ± 0.29 pc. By jointly fitting the available TESS transit light curves and follow-up radial velocity measurements, we find an orbital period of 0.9261 ± (0.5× 10^-4) days, a planetary radius of 1.72 ± 0.07 R_earth, and a mass of 7.42 ± 1.09 M_earth, implying a mean density of rho_planet = 8.06 ± 1.53 g cm^-3. HD 20329b joins the ~30 currently known USP planets with radius and Doppler mass measurements

3-O-(3′,3′-Dimethysuccinyl) Betulinic Acid Inhibits Maturation of the Human Immunodeficiency Virus Type 1 Gag Precursor Assembled In Vitro

3-O-(3′,3′-Dimethysuccinyl) betulinic acid (PA-457) has been shown to potently inhibit human immunodeficiency virus (HIV) replication in culture. In contrast to inhibitors that act upon the viral proteinase, PA-457 appears to block only the final maturational cleavage of p25CA-p2 to p24CA. However, attempts to replicate this effect in vitro using recombinant Gag have failed, leading to the hypothesis that activity is dependent upon the assembly state of Gag. Using a synthesis/assembly system for chimeric HIV type 1 Gag proteins, we have replicated the activity of PA-457 in vitro. The processing of assembled chimeric Gag can be inhibited by the addition of drug with only the final cleavage of p25CA-p2 to p24CA blocked. Consistent with our hypothesis and with previous findings, inhibition appears specific to Gag assembled into an immature capsid-like structure, since synthetic Gag that remains unassembled is properly processed in the presence of the compound. To further analyze the authenticity of the assay, PA-457 was tested in parallel with its inactive parental compound, betulinic acid. Betulinic acid had no effect upon p25 processing in this system. Analysis of a PA-457-resistant mutant, A1V, in this system pointed to more rapid cleavage as a possible mechanism for resistance. However, characterization of additional mutations at the cleavage site and in p2 suggests that resistance does not strictly correlate with the rate of cleavage. With the establishment of an in vitro assay for the detection of PA-457 activity, a more detailed characterization of its mechanism of action will be possible

Isolation of 32 Mycobacteriophages and Genomic Analysis of the Novel Mycobacteriophage, Roscoe

Thirty-two new mycobacteriophages were isolated from soil samples collected on or nearby Hope College in Holland, Michigan. All were capable of infecting Mycobacterium smegmatis and produced a variety of plaque morphologies based on size, shape, and clarity, consistent with the isolation of an assortment of different phages. Both lytic and temperate phages appear represented in this collection. Thirty-two purified phage stocks were used to prepare genomic DNA samples for restriction digest analysis. A comparison of those 32 digest results revealed few similarities among the group, further supporting our interpretation that most of the new phage isolates were distinct. One mycobacteriophage, Roscoe, was chosen for complete genome sequencing using the Ion Torrent Personal Genome Machine platform and comparative genomic analysis. The predominant plaque produced by Roscoe was 2-4 mm in diameter and displayed a clear center surrounded by a wide turbid comet-tailed ring after 24 hours of growth at 37°C. Comparison of the restriction digest pattern for Roscoe with more than 200 known mycobacteriophage genomes did not yield an exact match, suggesting Roscoe was a novel mycobacteriophage. Genome sequence data for Roscoe supported that prediction but also revealed a relationship to a large group of mycobacteriophages in Cluster B1. The genome of Roscoe is 68 Kb, 66.5% GC, and contains 103 genes in agreement with the genome characteristics of closely related phage. A detailed analysis of the complete genome sequence and comparison with sequenced members of this small and unique group of mycobacteriophages is the subject of the second semester of this yearlong course and is presented

Isolation of 35 Mycobacteriophages and Genomic Analysis of the Novel Mycobacteriophage, Glass

Thirty-five new mycobacteriophages were isolated from soil samples collected on or nearby Hope College in Holland, Michigan. All were capable of infecting Mycobacterium smegmatis and produced a variety of plaque morphologies based on size, shape, and clarity, consistent with the isolation of an assortment of different phages. Both lytic and temperate phages appear represented in this collection. Purified phage stocks were used to prepare genomic DNA samples for restriction digest analysis. A comparison of those 35 digest results revealed few similarities among the group, further supporting our interpretation that most of the new phage isolates were distinct. One mycobacteriophage, Glass, was chosen for complete genome sequencing using the Illumina MiSeq platform and comparative genomic analysis. The predominant plaque produced by Glass at 32°C was turbid and 0.5-1.0mm in diameter, while plaque produced at 42°C was clear and 1.0-1.5mm in diameter. Genome sequence data for Glass revealed a relationship to a group of 12 mycobacteriophages in Cluster B2. The genome of Glass is 67.5 Kb, 69.0% GC, and contains 91 genes in agreement with the genome characteristics of closely related phage. A detailed analysis of the complete genome sequence and comparison with sequenced members of this small and unique group of mycobacteriophages is the subject of the second semester of this yearlong course and is presented