This paper presents evidence that the two peptide antibiotics tyrocidine and linear gramicidin, produced by Bacillus brevis ATCC 8185, are required for the induction of sporulation in the producer organism. When tyrocidine synthesis was specifically blocked with 2-amino-3-hydroxy-3-phenylpropanoic acid [Mach, B., Reich, E., and Tatum, E. L. (1963) Proc. Natl Acad. Sci. USA, 50, 175-181], sporulation and gramicidin synthesis were inhibited, but both processes could be restored by the addition of tyrocidine. Certain other amino acids such as L-tyrosine inhibited both sporulation and peptide antibiotic synthesis in nitrogen-limited cultures. When either tyrocidine or linear gramicidin was added together with L-tyrosine, neither sporulation nor peptide antibiotic synthesis was restored. On the other hand, the addition of both tyrocidine and linear gramicidin effectively reversed the inhibition of sporulation by L-tyrosine. These experiments demonstrate that sporulation of B. brevis depends on either the endogenous synthesis or the addition of both tyrocidine and linear gramicidin. The fact that endogenous as well as exogenous peptides could effect sporulation argues against the involvement of artifacts, such as the depletion of intracellular nucleotide pools caused by the surfactant properties of added peptide antibiotics.
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http://dx.doi.org/10.1111/j.1432-1033.1982.tb07064.x | DOI Listing |
Biomol NMR Assign
December 2024
Department of Molecular Biophysics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Natural macrocyclic peptides produced by microorganisms serve as valuable resources for therapeutic compounds, including antibiotics, anticancer agents, and immune suppressive agents. Nonribosomal peptide synthetases (NRPSs) are responsible for the biosynthesis of macrocyclic peptides. NRPSs are large multimodular enzymes, and each module recognizes and incorporates one specific amino acid into the polypeptide product.
View Article and Find Full Text PDFJ Pept Sci
January 2024
Department of Medicinal Chemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
Natural macrocyclic peptides derived from microorganisms are medicinal resources that are important for the development of new therapeutic agents. Most of these molecules are biosynthesized by a nonribosomal peptide synthetase (NRPS). The thioesterase (TE) domain in NRPS is responsible for the macrocyclization of mature linear peptide thioesters in a final biosynthetic step.
View Article and Find Full Text PDFChemistry
September 2021
Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, 08028, Barcelona, Spain.
The introduction of a novel tetra-ortho-chloroazobenzene amino acid (CEBA) has enabled photoswitching of the antimicrobial activity of tyrocidine A analogues by using exclusively visible light, granting spatiotemporal control under benign conditions. Compounds bearing this photoswitchable amino acid become active upon irradiation with red light, but quickly turn-off upon exposure to other visible light wavelengths. Critically, sunlight quickly triggers isomerisation of the red light-activated compounds into their original trans form, offering an ideal platform for self-deactivation upon release into the environment.
View Article and Find Full Text PDFBiochimie
December 2020
BIOPEP(TM) Peptide Group, Department of Biochemistry, Stellenbosch University, Private Bag X1, Matieland, 7600, South Africa. Electronic address:
The tyrocidines and analogues are cationic cyclodecapeptides [cyclo (D-Phe-L-Pro-L-(Phe/Trp)-D-(Phe/Trp)-L-Asn-L-Gln-L-(Tyr/Phe/Trp)-L-Val-L-(Orn/Lys)-L-Leu], produced together with the neutral linear pentadecapeptide gramicidins, in the antibiotic tyrothricin complex by Brevibacillus parabrevis. Despite discovery 80 years ago, it was still uncertain whether these peptides are secreted or sequestered intracellularly. We resolved this by utilising high resolution electrospray mass spectrometry to confirm the predominantly intracellular sequestration of the peptides in the tyrothricin complex.
View Article and Find Full Text PDFSci Rep
March 2019
Institute of Biology II, University of Freiburg, 79104, Freiburg, Germany.
Non-ribosomal peptide synthetases (NRPSs) are large, modular enzymes that produce bioactive peptides of tremendous structural and chemical diversity, due to the incorporation, alongside the canonical 20 amino acids, of non-proteinogenic amino acids, fatty acids, sugars and heterocyclic rings. For linear NRPSs, the size and composition of the peptide product is dictated by the number, order and specificity of the individual modules, each made of several domains. Given the size and complexity of NRPSs, most in vitro studies have focused on individual domains, di-domains or single modules extracted from the full-length proteins.
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