RT info:eu-repo/semantics/article
T1 Analysis of substrate specificity of cytochrome P450 monooxygenases involved in trichothecene toxin biosynthesis
A1 Cardoza, Rosa E.
A1 McCormick, Susan P.
A1 Martínez Reyes, Natalia
A1 Rodríguez Fernández, Joaquín
A1 Busman, Mark
A1 Proctor, Robert H
A1 Gutiérrez Martín, Santiago
A2 Microbiologia
K1 Biotecnología
K1 Cytochrome P450 monooxygenases
K1 Trichothecene biosynthesis
K1 Substrate specificity
K1 Gene deletion
K1 Gene expression
K1 Evolutionary relationships
K1 2414 Microbiología
AB [EN]Trichothecenes are a structurally diverse family of toxic secondary metabolites produced by certain species of multiple fungal genera. All trichothecene analogs share a core 12,13-epoxytrichothec-9-ene (EPT) structure but differ in presence, absence and types of substituents attached to various positions of EPT. Formation of some of the structural diversity begins early in the biosynthetic pathway such that some producing species have few trichothecene biosynthetic intermediates in common. Cytochrome P450 monooxygenases (P450s) play critical roles in formation of trichothecene structural diversity. Within some species, relaxed substrate specificities of P450s allow individual orthologs of the enzymes to modify multiple trichothecene biosynthetic intermediates. It is not clear, however, whether the relaxed specificity extends to biosynthetic intermediates that are not produced by the species in which the orthologs originate. To address this knowledge gap, we used a mutant complementation-heterologous expression analysis to assess whether orthologs of three trichothecene biosynthetic P450s (TRI11, TRI13 and TRI22) from Fusarium sporotrichioides, Trichoderma arundinaceum, and Paramyrothecium roridum can modify trichothecene biosynthetic intermediates that they do not encounter in the organism in which they originated. The results indicate that TRI13 and TRI22 could not modify the intermediates that they do not normally encounter, whereas TRI11 could modify an intermediate that it does not normally encounter. These findings indicate that substrate promiscuity varies among trichothecene biosynthetic P450s. One structural feature that likely impacts the ability of the P450s to use biosynthetic intermediates as substrates is the presence and absence of an oxygen atom attached to carbon atom 3 of EPT.
PB Springer
SN 0175-7598
LK https://hdl.handle.net/10612/17568
UL https://hdl.handle.net/10612/17568
NO Cardoza, R.E., McCormick, S.P., Martínez-Reyes, N. et al. Analysis of substrate specificity of cytochrome P450 monooxygenases involved in trichothecene toxin biosynthesis. Appl Microbiol Biotechnol 108, 1–21 (2024). https://doi.org/10.1007/s00253-023-12950-1
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 20-may-2024