A 24-membered ring macrolide compound, macrolactin A has potential applications in pharmaceuticals for its anti-infectious and antiviral activity. In this study, macrolactin A was produced by a marine bacterium, which was identified as Bacillus subtilis by 16S ribosomal RNA (rRNA) sequence analysis. Electrospray ionization mass spectrometry (ESI/MS) and nuclear magnetic resonance (NMR) spectroscopy analyses were used to characterize this compound. To improve the production, response surface methodology (RSM) involving Box-Behnken design (BBD) was employed. Faeces bombycis, the main by-product in sericulture, was used as a nitrogen source in fermentation. The interactions between three significant factors, F. bombycis, soluble starch, and (NH4)2SO4 were investigated. A quadratic model was constructed to fit the production and the factors. Optimum medium composition was obtained by analysis of the model. When cultivated in the optimum medium, the production of macrolactin A was increased to 851 mg/L, 2.7 times as compared to the original. This study is also useful to find another way in utilizing F. bombycis.
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http://dx.doi.org/10.1631/jzus.B1200153 | DOI Listing |
Int J Biol Macromol
January 2025
Department of Chemistry, Lady Brabourne College, Kolkata 700017, India. Electronic address:
The lipocalin carrier protein, β-lactoglobulin (β-lg), stands out as a crucial protein in the food industry, known for its ability to effectively bind with hydrophobic small molecules. However, it was unclear how β-lg interacts with macrocyclic molecules. In this research, we focused on two key aspects.
View Article and Find Full Text PDFJ Pept Sci
December 2024
Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
Oligourea foldamers are known to fold into 2.5-helices, stabilized by three-centered hydrogen bonds, which makes them conformationally more rigid than peptides. Nevertheless, the folding propensity and conformational stability in solution depend on the length of the oligomer, as well as the temperature, solvent, and so forth.
View Article and Find Full Text PDFJ Med Chem
July 2024
Department of Chemistry and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee 37235, United States.
Cyclic oligomeric depsipeptides (COD) are a structural class within naturally occurring compounds with a wide range of biological activity. Verticilide is a COD (24-membered ring) that was identified by its inhibition of insect ryanodine receptor (RyR). We have since found that the enantiomer of verticilide (-verticilide, ) is a potent inhibitor of mammalian RyR2, a cardiac calcium channel, and therefore a potential antiarrhythmic agent.
View Article and Find Full Text PDFMol Pharmacol
February 2024
Vanderbilt Center for Arrhythmia Research and Therapeutics, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee (A.G., T.Q.D. K.K., D.J.B., P.A.R., B.C.K.); Vanderbilt Department of Chemistry and Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee (M.P.T., A.N.S., J.N.J.); Pharmaceutical Sciences Research Center, Lipscomb University College of Pharmacy, Nashville, Tennessee (W.S.A.); Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, Minnesota (J.A.S., R.L.C., R.T.R.); and School of Biomedical Sciences and Pharmacy, University of Newcastle and Hunter Medical Research Institute, Callaghan, NSW 2308, Australia (D.R.L.)
Intracellular Ca leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor (+)-verticilide (-1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product (-(-)-verticilide). Here, we examined its 18-membered ring-size oligomer (-verticilide B1; "-B1") in RyR2 single channel and [H]ryanodine binding assays, and in cardiomyocytes and mice, a gene-targeted model of SCD.
View Article and Find Full Text PDFUnlabelled: Ca leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor (+)-verticilide ( -1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product ( -(-)-verticilide). Here, we examined its 18-membered ring-size oligomer ( -verticilide B1; " -B1") in single RyR2 channel assays, [ H]ryanodine binding assays, and in cardiomyocytes and mice, a gene-targeted model of SCD.
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