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11 protocols using uracil

1

Functional Expression of Acyltransferases in Yeast

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Example 18

The constructs pYes2_CpDGAT1, pYes2_CpDGAT1Ala, and pYes2_CpDGAT1trunc were transformed into S. cerevisiae strain H1246 (W303; MATα are1-Δ::HIS3 are2-Δ::LEU2 dga1::KanMX4 lro1-Δ::TRP1 ADE2 met ura3) (Sandager et al., 2002, J. Biol. Chem., 277:6478-82) using PEG/lithium acetate method (Gietz et al., 1995, Yeast, 11:355-60). The yeast cells harboring the empty pYes2 vector were used as negative control. Transformants were selected by uracil prototrophy on yeast synthetic medium (YSM) containing 2% (w/v) glucose and lacking uracil (Invitrogen, Carlsbad, Calif. USA). For functional expression YSM containing 2% (w/v) raffinose was inoculated with the yeast transformants and grown at 28° C. for 24 h in a shaker at 350 rpm. For induction, YSM containing 2% (w/v) galactose was inoculated with raffinose-grown cultures to obtain an OD of 0.2 at 600 nm and grown at 28° C. for 48 h. For fatty acid feeding experiments cultures were grown for 2.5 hs in YSM containing 2% galactose followed by addition of 1% (w/v) Tergitol-40 and 250 μM of the appropriate fatty acid substrate. Cells were harvested by centrifugation, washed twice with 0.1% NaHCO3, freeze-dried and used for fatty acid, TAG analysis and microsome isolation.

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2

Functional Expression of CpDGAT1 in Yeast

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Example 18

The constructs pYes2_CpDGAT1, pYes2_CpDGAT1Ala, and pYes2_CpDGAT1trunc were transformed into S. cerevisiae strain H1246 (W303; MATα are1-Δ::HIS3 are2-Δ::LEU2 dga1::KanMX4 lro1-Δ::TRP1 ADE2 met ura3) (Sandager et al., 2002, J. Biol. Chem., 277:6478-82) using PEG/lithium acetate method (Gietz et al., 1995, Yeast, 11:355-60). The yeast cells harboring the empty pYes2 vector were used as negative control. Transformants were selected by uracil prototrophy on yeast synthetic medium (YSM) containing 2% (w/v) glucose and lacking uracil (Invitrogen, Carlsbad, Calif. USA). For functional expression YSM containing 2% (w/v) raffinose was inoculated with the yeast transformants and grown at 28° C. for 24 h in a shaker at 350 rpm. For induction, YSM containing 2% (w/v) galactose was inoculated with raffinose-grown cultures to obtain an OD of 0.2 at 600 nm and grown at 28° C. for 48 h. For fatty acid feeding experiments cultures were grown for 2.5 hs in YSM containing 2% galactose followed by addition of 1% (w/v) Tergitol-40 and 250 μM of the appropriate fatty acid substrate. Cells were harvested by centrifugation, washed twice with 0.1% NaHCO3, freeze-dried and used for fatty acid, TAG analysis and microsome isolation.

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3

Fungal Growth and Development Protocols

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The A. nidulans strains used in this study are listed in Table 1. Fungal strains were grown on solid or liquid minimal media with 1% glucose (MMG) [47 (link)]. For auxotroph mutants, uridine (Acros Organics, USA), uracil (Acros Organics), and pyridoxine (Sigma-Aldrich, USA) were supplemented in the media. Sexual media (SM) was used to induce sexual development [48 (link)]. To observe developmental phenotypes, the strains were point inoculated in solid MMG or SM and cultured at 37°C for 5-7 days. For sterigmatocystin extraction, the strains were cultured in liquid complete media (CM) at 30°C for 7 days. To collect fresh conidia, each strain was incubated in solid MMG at 37°C for 2 days. For amplification of the plasmid used to generate the complemented strains, Escherichia coli DH5α (Enzynomics, Korea) cells were grown in a Luria–Bertani medium (BD Difco, USA) with ampicillin (100 μg/ml) (Sigma-Aldrich).
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4

Synthesis and Characterization of Adenine-Rhodamine Conjugate

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Uracil (≥99% purity) and adenine (>99.5% purity) were purchased from Acros Organics (Geel, Belgium). Rhodamine 6G (R6G), polyethylene glycol (PEG, average molecular mass: 1900–2200 g/mol), dimethylformamide (DMF), potassium tert-butoxide (t-BuOK), triethylamine (TEA), deuterated chloroform (CDCl3), and deuterium oxide (D2O) were obtained from Sigma-Aldrich Chemical (Milwaukee, WI, USA) at the highest purity available. The HPLC-grade organic solvents were used as received from TEDIA (Fairfield, OH, USA). Phosphate-buffered saline (PBS), Dulbecco’s modified Eagle’s medium (DMEM), fetal bovine serum (FBS), penicillin-streptomycin, trypsin-EDTA, trypan blue, 4′,6-diamidino-2-phenylindole (DAPI), the Dead Cell Apoptosis Kit with Brilliant Violet-421™ Annexin V (BV421-Annexin V), and Ghost Dye™ Red 780 (GDR780) were purchased from Thermo Fisher Scientific (Waltham, MA, USA). All chemicals and reagents were employed as received. adenine-functionalized rhodamine derivative (A-R6G) and PEG diacrylate (PEGDA, number average molecular weight (Mn) = ~2000) were synthesized and characterized according to procedures that have been described previously [31 (link),32 (link),33 (link)].
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5

Evaluating Homologues and Hold-up Markers

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The injected series of homologues (n-alkyl benzenes, n-alkyl phenones, and n-alkyl ketones) and the hold-up volume markers candidates (acetone, urea, dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), formamide, thiourea, uracil, potassium bromide, and lithium nitrate) were purchased from Acros Organics (Geel, Belgium), Alfa Aesar (Ward Hill, MA, USA), Baker, Carlo Erba (Emmendingen, Germany), Fluka (Buchs, Switzerland), Merck, Prolabo (Sion, Switzerland), and Sigma-Aldrich (St. Louis, MO, USA), all of high purity grade (≥97%). Stock solutions of the injected analytes were prepared in methanol at a concentration of 5 mg mL−1 except for inorganic salts, which were dissolved in water. n-Alkyl ketones were injected at stock solution concentration because of their low UV-Vis absorbance, but the rest of the analytes were diluted to 0.5 mg mL−1 before injection.
Water was obtained from a Milli-Q plus system from Millipore (Billerica, MA, USA) with a resistivity of 18.2 MΩ cm. Acetonitrile and methanol were HPLC gradient grade and from Labkem (Dublin, Ireland) and Chem-Lab (Zedelgem, Belgium).
Ammonium acetate (Sigma-Aldrich, >98%) was used in the evaluation of the effect of salt concentration in Acetonitrile/water mobile phases, in a range between 5 and 20 mM.
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6

Defined Minimal Medium for Yeast

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Defined minimal medium contained 6.7 g/L of yeast nitrogen base without amino acids (catalog no. Y0626; Sigma-Aldrich, MO, USA), 20 g/L of glucose, 380 mg/L leucine (catalog no. 172130250; Acros Organics, CA, USA), 76 mg/L uracil (catalog no. 157301000; Acros Organics, CA, USA), and various concentrations of [EMIM][OAc] (>95% purity) (IoLiTec, AL, USA). Synthetic complete medium without leucine and uracil (SC-Leu-Ura) was prepared with 6.7 g/L of yeast nitrogen base without amino acids; 1.46 g/L of yeast synthetic dropout medium supplement without uracil, leucine, and tryptophan (catalog no. Y1771; Sigma-Aldrich, MO, USA); 76 mg/L tryptophan (catalog no. 172110250; Acros Organics, CA, USA), 20 g/L glucose, and various concentrations of [EMIM][OAc]. SC without leucine (SC-Leu) was prepared by adding 76 mg/L uracil to SC-Leu-Ura medium.
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7

Culturing Aspergillus flavus Strains

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Table 1 shows a list of strains used in this study. To culture A. flavus strains, glucose minimal medium with 0.1% yeast extract (MMYE) was used [50 (link)]. A. flavus NRRL 3357.5 (pyrG- auxotrophic mutant strain) was used for transformation and was grown on MMYE with supplements (5 mM uridine (Acros organics, NJ, USA) and 10 mM uracil (Acros organics, NJ, USA)) [51 (link)].
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8

Defined Minimal Media for Yeast Culture

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Growth medium. Defined minimal media contained 6.7 g/L of yeast nitrogen base without amino acids (cat# Y0626, Sigma-Aldrich, MO, USA), 20 g/L of glucose, 380 mg/L leucine (cat# 172130250, Acros Organics, CA, USA), 76 mg/L uracil (cat# 157301000, Acros Organics, CA,
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9

HPLC-Grade Solvents for NaPSS Analysis

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HPLC-grade solvents: ACN was purchased from EMD Millipore Chemicals (Billerica, MA, USA), unstabilized THF and MeOH from Sigma-Aldrich (St. Louis, MO, USA). Deionized (DI) water was “in-house” from Barnstead Nanopure Diamond, D11911. Sodium sulfate was purchased from Sigma-Aldrich (St. Louis, MO, USA) and uracil (Acros Organics) from Thermo Fisher Scientific (Pittsburgh, PA, USA). NaPSS standards were purchased from Phenomenex (Torrance, CA, USA). Molar mass dispersities of all NaPSS standards were ≤1.20, and molar mass values given here correspond to the peakaverage molar mass (average molar mass at peak apex, Mp); both values were supplied by the vendor.
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10

Potato Dextrose Agar Supplementation

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39 g Potato Dextrose Agar (PDA, Sigma–Aldrich, #70139-500 G), 5 g uridine,2 g uracil, and 1 mg/mL 5-fluoroorotic acid (ThermoFisher, #R0812).
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