Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively. Cryo-electron microscopy analysis of AuraA and its two ternary complex structures reveal two distinct modes for receptor binding, demonstrating a tolerance for altered orientations of highly similar receptors. The mutation experiments further demonstrate the promiscuity of AuraA towards imidazole-C-dimethylallylation. In this work, we also characterize a case of AuraA mutant-catalyzed dimethylallylation of imidazole moiety, offering available structural insights into the utilization and engineering of dimethylallyl tryptophan synthase family prenyltransferases.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696170 | PMC |
| http://dx.doi.org/10.1038/s41467-024-55537-8 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization and structural analysis of a versatile aromatic prenyltransferase for imidazole-containing diketopiperazines.
Nat Commun
January 2025
Key Laboratory of Marine Drugs Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, P R China.
Prenylation modifications of natural products play essential roles in chemical diversity and bioactivities, but imidazole modification prenyltransferases are not well investigated. Here, we discover a dimethylallyl tryptophan synthase family prenyltransferase, AuraA, that catalyzes the rare dimethylallylation on the imidazole moiety in the biosynthesis of aurantiamine. Biochemical assays validate that AuraA could accept both cyclo-(L-Val-L-His) and cyclo-(L-Val-DH-His) as substrates, while the prenylation modes are completely different, yielding C2-regular and C5-reverse products, respectively.
View Article and Find Full Text PDFFerroptosis: when metabolism meets cell death.
Physiol Rev
December 2024
Institute of Metabolism and Cell Death, Molecular Targets and Therapeutics Center, Helmholtz Zentrum München, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany.
We present here a comprehensive update on recent advancements in the field of ferroptosis, with a particular emphasis on its metabolic underpinnings and physiological impacts. After briefly introducing landmark studies that have helped to shape the concept of ferroptosis as a distinct form of cell death, we critically evaluate the key metabolic determinants involved in its regulation. These include the metabolism of essential trace elements such as selenium and iron; amino acids such as cyst(e)ine, methionine, glutamine/glutamate and tryptophan; and carbohydrates, covering glycolysis, the citric acid cycle, the electron transport chain and the pentose phosphate pathway.
View Article and Find Full Text PDFGeranylation of Cyclic Dipeptides and Naphthols by the Fungal Prenyltransferase CdpC3PT_F253G.
Chembiochem
November 2024
Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People's Republic of China.
Prenyl modification often improves the biological activities of compounds. Prenyltransferases have attracted attention as environmentally friendly biocatalysts for catalyzing prenyl modification of compounds. Compared to dimethylallyl modifications, research on geranyl modifications is relatively limited.
View Article and Find Full Text PDFPrenylation of aromatic amino acids and plant phenolics by an aromatic prenyltransferase from Rasamsonia emersonii.
Appl Microbiol Biotechnol
July 2024
Laboratory of Food Chemistry, Wageningen University, Bornse Weilanden 9, 6708 WG, Wageningen, The Netherlands.
Dimethylallyl tryptophan synthases (DMATSs) are aromatic prenyltransferases that catalyze the transfer of a prenyl moiety from a donor to an aromatic acceptor during the biosynthesis of microbial secondary metabolites. Due to their broad substrate scope, DMATSs are anticipated as biotechnological tools for producing bioactive prenylated aromatic compounds. Our study explored the substrate scope and product profile of a recombinant RePT, a novel DMATS from the thermophilic fungus Rasamsonia emersonii.
View Article and Find Full Text PDFTryptophan-Centric Bioinformatics Identifies New Lasso Peptide Modifications.
Biochemistry
April 2024
Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) defined by a macrolactam linkage between the N-terminus and the side chain of an internal aspartic acid or glutamic acid residue. Instead of adopting a branched-cyclic conformation, lasso peptides are "threaded", with the C-terminal tail passing through the macrocycle to present a kinetically trapped rotaxane conformation. The availability of enhanced bioinformatics methods has led to a significant increase in the number of secondary modifications found on lasso peptides.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!