Aclacinomycin A (ACM-A) is an anthracycline antitumor agent widely used in clinical practice. The current industrial production of ACM-A relies primarily on chemical synthesis and microbial fermentation. However, chemical synthesis involves multiple reactions which give rise to high production costs and environmental pollution. Microbial fermentation is a sustainable strategy, yet the current fermentation yield is too low to satisfy market demand. Hence, strain improvement is highly desirable, and tremendous endeavors have been made to decipher biosynthesis pathways and modify key enzymes. In this review, we comprehensively describe the reported biosynthesis pathways, key enzymes, and, especially, catalytic mechanisms. In addition, we come up with strategies to uncover unknown enzymes and improve the activities of rate-limiting enzymes. Overall, this review aims to provide valuable insights for complete biosynthesis of ACM-A.
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http://dx.doi.org/10.3390/molecules28062761 | DOI Listing |
J Fluoresc
January 2025
Department of Chemical Sciences, University of Johannesburg, Doornfontein, Johannesburg, South Africa.
Point of Care (POC) diagnosis provides an effective approach for controlling and managing Neglected Tropical Diseases (NTDs). Electrochemical biosensors are well-suited for molecular diagnostics due to their high sensitivity, cost-effectiveness, and ease of integration into POC devices. Schistosomiasis is a prominent NTD highly prevalent in Africa, Asia, and Latin America, with significant socioeconomic implications such as discrimination, reduced work capacity, or mortality, perpetuating the cycle of poverty in affected regions worldwide.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Faculty of Pharmaceutical Sciences, Shenzhen University of Advanced Technology, Shenzhen 518107, China.
The synthesis of chiral tetrahydroquinolines (THQs) has garnered significant interest from medicinal chemists due to their frequent presence as pharmacophores in bioactive compounds. While existing synthetic methods have primarily focused on THQs with single or multiple endocyclic chiral centers, the selective construction of THQs with both and cyclic chiral centers remains a significant challenge that requires further development. This study introduces a dynamic kinetic resolution (DKR)-based transfer hydrogenation of racemic 2-substituted quinolines, which yields structurally novel chiral THQs with consecutive and cyclic chiral centers in excellent yields and stereoselectivities (59 examples, with generally >20:1 dr and >90% ee, up to three consecutive stereocenters).
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry and Chemical Biology, TU Dortmund University and Drug Discovery Hub Dortmund (DDHD), Zentrum für Integrierte Wirkstoffforschung (ZIW), Otto-Hahn-Strasse 4a, Dortmund 44227, Germany.
Gastrointestinal stromal tumors (GIST), driven by KIT and PDGFRA mutations, are the most common mesenchymal tumors of the gastrointestinal tract. Although tyrosine kinase inhibitors (TKIs) have advanced treatment, resistance mutations and off-target toxicity limit their efficacy. This study develops covalent TKIs targeting drug-resistant GIST through structure-based design, synthesis, and biological evaluation.
View Article and Find Full Text PDFOrg Lett
January 2025
Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
A novel class of bis-8-aryl-isoquinoline () bis-alkylamine iron complexes, Fe()(OTf) and Fe()(OTf) ( = dipyrrolidinyl or = ,'-dimethylcyclohexyl-diamine), for asymmetric oxidation reactions is reported. The scalable divergent synthesis of 8-aryl-3-formylisoquinolines (), the key intermediates in preparing these ligands, enables precise structural and electronic tuning around the metal center. The enantioselective epoxidation and hydroxy carbonylation of conjugated alkenes, mediated by the Fe() catalyst with HO as the oxidant, demonstrates the potential of these redox Fe[N] catalysts in inducing face selection in oxygen transfer transformations.
View Article and Find Full Text PDFDalton Trans
January 2025
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China.
Treatment of amidinato-based magnesium ethyl compounds LMgEt [L = PrPNC(Bu)NAr; Ar = 2,6-PrCH (La) or 2,6-(PhCH)-4-Pr-(CH) (Lb)] with Ni(COD) (COD: 1,5-cyclooctadiene) afforded heterotrimetallic Mg-Ni-Mg complexes [(LMg)Ni(CH)] through β-H elimination. These complexes exhibit approximately linear Mg-Ni-Mg linkage with the central nickel arranged in a planar configuration; the Ni(CH) unit can be considered as nickela-bis-cyclopropane. Reaction of [(LMg)Ni(CH)] with tetrahydrofuran (THF) gave a coordination product [(LMg·THF)Ni(CH)], in which the central structure remained intact and THF coordinated to two magnesium atoms respectively.
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