Cascade reactions during coronafacic acid biosynthesis: elongation, cyclization, and functionalization during Cfa7-catalyzed condensation.
Herein, the biogenesis of the hydrindane ring system within coronafacic acid (CFA) has been investigated. These studies reveal that in addition to the canonical polyketide chain elongation and functionalization encoded by type I polyketide synthase (PKSs), cascade reactions can take place during assembly line-like biosynthesis. Indeed, upon Cfa7-catalyzed Claisen condensation between enzyme-bound malonate and an N-acetylcysteamine (SNAC) thioester, latent reactivity within the elongated enzyme-bound intermediate is unveiled. This reactivity translates into an intramolecular cyclization, which can proceed in a facile manner as observed by the enzyme-independent cyclization of a linear beta-ketothioester intermediate.
Strieter
Eric R
ER
Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Koglin
Alexander
A
Aron
Zachary D
ZD
Walsh
Christopher T
CT
D002384:Catalysis; D003500:Cyclization; D003543:Cysteamine / Q000031:analogs & derivatives / Q000378:metabolism; D007192:Indenes / Q000378:metabolism*; D008314:Malonates / Q000378:metabolism; D048630:Polyketide Synthases / Q000378:metabolism; D016958:Pseudomonas putida / Q000201:enzymology / Q000378:metabolism
D007192:Indenes; D008314:Malonates; D003543:Cysteamine; C084266:coronafacic acid; D048630:Polyketide Synthases; C030290:malonic acid