Efficient and Selective Biosynthesis of a Precursor-Directed FK506 Analogue: Paving the Way for Click Chemistry

• Published in: Journal of natural products (Washington, D.C.) Vol. 88; no. 3; pp. 619 - 630
• Main Authors: Goranovič, Dušan, Jenko, Branko, Ramšak, Barbara, Podgoršek Berke, Ajda, Bedrač, Leon, Horvat, Jaka, Šala, Martin, Makuc, Damjan, Carriche, Guilhermina M., Silva, Luana, Lopez Krol, Aleksandra, Pšeničnik, Alen, Durán Alonso, María Beatriz, Avbelj, Martina, Stavber, Stojan, Plavec, Janez, Sparwasser, Tim, Müller, Rolf, Kosec, Gregor, Fujs, Štefan, Petković, Hrvoje
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society and American Society of Pharmacognosy 28.03.2025
• Subjects: biosynthesis; carbon; Click Chemistry; cytotoxicity; domain; Humans; immunosuppression; immunosuppressive agents; Immunosuppressive Agents - chemistry; Immunosuppressive Agents - pharmacology; moieties; Molecular Structure; nonribosomal peptides; Peptide Synthases - metabolism; polyketide synthases; Polyketide Synthases - metabolism; polyketides; Tacrolimus - analogs & derivatives; Tacrolimus - chemistry; Tacrolimus - metabolism

The medically important immunosuppressant FK506 is a structurally complex macrolactone biosynthesized by a combined polyketide synthase and a nonribosomal peptide synthetase enzyme complex. Its acyltransferase domain 4 (AT4) selects an unusual extender unit, resulting in an allyl moiety on carbon 21...