Two new geldanamycin (GDM) analogues, (4S)-4,5-dihydro-4-hydroxygeldanamycin (1) and (4R)-4,5-dihydro-4-hydroxygeldanamycin (2), were identified from Streptomyces hygroscopicus 17997. Compounds 1 and 2 were not normal intermediates of GDM biosynthesis but shunt products of C-4,5 oxidation catalyzed by GdmP, a cytochrome P450 oxidase acting as a desaturase in GDM biosynthesis. Preliminary assays implied that, compared with GDM, 1 and 2 exhibited decreased cytotoxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/np3001738 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Positive regulation of a LuxR family protein, MilO, in mildiomycin biosynthesis.
Appl Environ Microbiol
December 2024
State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Mildiomycin is a representative peptidyl nucleoside antibiotic and was first isolated from , which has been used as an important biological agent to control powdery mildew in plants. Despite its importance, the biosynthetic pathways and regulatory mechanisms remain to be fully elucidated. In this study, we identified MilO as a positive pathway-specific regulator of mildiomycin biosynthesis in the heterologous host .
View Article and Find Full Text PDFA Case of Pulmonary Arteriovenous Shunt Diagnosed by Microbubble Test via a Swan-Ganz Catheter.
Cureus
December 2024
Department of Cardiology, Japanese Red Cross Maebashi Hospital, Maebashi, JPN.
When encountering severe hypoxemia that does not respond to oxygen supplementation, it is essential to consider underlying right-to-left shunting. Among various diagnostic approaches, the microbubble test via transthoracic echocardiography (TTE) is a simple, noninvasive method for detecting pulmonary arteriovenous shunts, particularly in hepatopulmonary syndrome (HPS). Although microbubbles are usually administered peripherally, using a Swan-Ganz (SG) catheter to inject microbubbles directly into the pulmonary artery may provide even more definitive diagnostic information.
View Article and Find Full Text PDFMetabolic Blockade-Based Genome Mining of SCSIO 07745: Discovery and Biosynthetic Pathway of Aminoquinolinone Alkaloids Bearing 6/6/5 Tricyclic and 6/6/6/5 Tetracyclic Scaffolds.
Org Lett
December 2024
Key Laboratory of Chemical Biology (Ministry of Education), Shandong Basic Science Research Center (Pharmacy), School of Pharmaceutical Sciences, Shandong University, Jinan, Shandong 250012, China.
Metabolic blockade-based genome mining of the marine sediment-derived SCSIO 07745 led to the discovery of 11 novel aminoquinolinone alkaloids, oxazoquinolinones A-J (-), characterized by an oxazolidone[3,2-α]quinoline-5,8-dione scaffold, and oxazoquinolinone K (), featuring an unprecedented fused 6/6/6/5 tetracyclic core ring system. Additionally, 5 new biosynthetic intermediates or shunt products (-) and a known metabolite sannanine () were identified. Their structures were elucidated by extensive spectroscopic analyses and a comparison of electronic circular dichroism and single-crystal X-ray diffraction.
View Article and Find Full Text PDFInsights and progress on the biosynthesis, metabolism, and physiological functions of gamma-aminobutyric acid (GABA): a review.
PeerJ
December 2024
Department of Medicine, Qingdao Binhai University, Qingdao, Shandong, China.
GABA (γ-aminobutyric acid) is a non-protein amino acid that occurs naturally in the human brain, animals, plants and microorganisms. It is primarily produced by the irreversible action of glutamic acid decarboxylase (GAD) on the α-decarboxylation of L-glutamic acid. As a major neurotransmitter in the brain, GABA plays a crucial role in behavior, cognition, and the body's stress response.
View Article and Find Full Text PDFMechanistic Insights Into Post-translational α-Keto-β-Amino Acid Formation by a Radical S-Adenosyl Methionine Peptide Splicease.
Angew Chem Int Ed Engl
December 2024
ETH Zurich: Eidgenossische Technische Hochschule Zurich, Institute of Microbiology, Vladimir-Prelog-Weg 1-5/10, HCI G433, 8008, Zürich, SWITZERLAND.
Radical S-adenosyl methionine enzymes catalyze a diverse repertoire of post-translational modifications in protein and peptide substrates. Among these, an exceptional and mechanistically obscure example is the installation of α-keto-β-amino acid residues by formal excision of a tyrosine-derived tyramine unit. The responsible spliceases are key maturases in a widespread family of natural products termed spliceotides that comprise potent protease inhibitors, with the installed β-residues being crucial for bioactivity.
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!