RT info:eu-repo/semantics/article
T1 Transcriptional studies on a Streptomyces clavuligerus oppA2 deletion mutant: N-Acetylglycyl-Clavaminic acid is an intermediate of clavulanic acid biosynthesis
A1 Álvarez Álvarez, Rubén
A1 Rodríguez García, Antonio
A1 Martínez Burgo, Yolanda
A1 Martín Martín, Juan Francisco
A1 Liras Padín, Paloma
A2 Microbiologia
K1 Biotecnología
K1 Streptomyces clavuligerus
K1 Oligopeptide-binding protein OppA2
K1 oppA2-null mutant
K1 Antibotics biosynthesis regulation
K1 Clavulanic acid gene cluster
K1 Transcriptomics
K1 2414.01 Antibióticos
K1 2415.01 Biología Molecular de Microorganismos
AB [EN] The oppA2 gene encodes an oligopeptide-binding protein similar to the periplasmic substrate-binding proteins of the ABC transport systems. However, oppA2 is an orphan gene, not included in an ABC operon. This gene is located in the clavulanic acid (CA) gene cluster of Streptomyces clavuligerus and is essential for CA production. A transcriptomic study of the oppA2-null mutant S. clavuligerus ΔoppA2::aac showed changes in the expression levels of 233 genes from those in the parental strain. These include genes for ABC transport systems, secreted proteins, peptidases, and proteases. Expression of the clavulanic acid, clavam, and cephamycin C biosynthesis gene clusters was not significantly affected in the oppA2 deletion mutant. The genes for holomycin biosynthesis were upregulated 2-fold on average, and the level of upregulation increased to 43-fold in a double mutant lacking oppA2 and the pSCL4 plasmid. Strains in which oppA2 was mutated secreted into the culture the compound N-acetylglycyl-clavaminic acid (AGCA), a putative intermediate of CA biosynthesis. A culture broth containing AGCA, or AGCA purified by liquid chromatography-mass spectrometry (LC-MS), was added to the cultures of various non-CA-producing mutants. Mutants blocked in the early steps of the pathway restored CA production, whereas mutants altered in late steps did not, establishing that AGCA is a late intermediate of the biosynthetic pathway, which is released from the cells when the oligopeptide-binding protein OppA2 is not available
PB American Society for Microbiology (ASM)
SN 0099-2240
LK https://hdl.handle.net/10612/18073
UL https://hdl.handle.net/10612/18073
NO Álvarez-Álvarez, R., Rodríguez-García, A., Martínez-Burgo, Y., Martín, J. F., & Liras, P. (2018). Transcriptional studies on a Streptomyces clavuligerus oppA2 deletion mutant: N-acetylglycyl-clavaminic acid is an intermediate of clavulanic acid biosynthesis. Applied and environmental microbiology, 84(22), e01701-18. https://doi.org/10.1128/AEM.01701-18
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 15-jun-2024