Isoepoxydon, a new metabolite of the patulin pathway in Penicillium urticae.
A patulin-negative mutant (J1) of Penicillium urticae (N.R.R.L. 2159A) was known to accumulate about 100mg per litre quantities of the 5,6-epoxygentisyl quinone, (-)-phyllostine and another metabolite (UIII). Both were derived from acetate and hence were polyketides. Purified UIII (m.p. 53 degrees C, [alpha](32) (D)+206 degrees , lambda(methanol) (max.) 240nm; epsilon 3806 litre.mol(-1).cm(-1)) was characterized as a partially reduced derivative of (-)-phyllostine and was found to be a diastereoisomer of the known phytotoxin, (+)-epoxydon. Hence its designation as (+)-iso- or epi-epoxydon. From (1)H n.m.r. and c.d. data the stereochemistry of the epoxide ring in (+)-isoepoxydon was determined to be identical with that in (+)-epoxydon (i.e. R,R) but the configuration of the secondary alcohol at C-4 was S rather than R as in (+)-epoxydon. Isoepoxydon (compound UIII) is therefore (4S,5R,6R)-5,6-epoxy-4-hydroxy-2-hydroxymethylcyclohex-2-en-1-one. The boat conformation in which the C-4 hydroxy group is axial is preferred. In the range of 1mm to 5mm, the antibiotic activity of (+)-isoepoxydon against Bacillus subtilis sp. was 56% of that obtained with patulin. Over a period of 1 to 3h, [(14)C]isoepoxydon was efficiently converted into patulin by a shake culture of the parent strain of P. urticae. The precursor relationship of isoepoxydon to patulin was confirmed by feeding unlabelled isoepoxydon (1mm) to a washed-cell suspension of a mutant (J2) in which, over a period of 3 to 5h, a better than 60% conversion into patulin was attained. The enzymic relationship between isoepoxydon and phyllostine and their positions in the late portion of the patulin biosynthetic pathway are discussed.
D000107:Acetylation; D000900:Anti-Bacterial Agents; D055598:Chemical Phenomena; D002621:Chemistry; D003511:Cyclohexanols / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D004852:Epoxy Compounds / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D004988:Ethers, Cyclic / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009154:Mutation; D010365:Patulin / Q000096:biosynthesis*; D010407:Penicillium / Q000235:genetics / Q000378:metabolism*; D011714:Pyrans / Q000096:biosynthesis*; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D003511:Cyclohexanols; D004852:Epoxy Compounds; D004988:Ethers, Cyclic; D011714:Pyrans; C022243:isoepoxydon; D010365:Patulin