title: Reveromycins revealed: new polyketide spiroketals from Australian marine-derived and terrestrial Streptomyces spp. A case of natural products vs. artifacts.
abstract: Chemical analysis of fermentation products from two Australian Streptomyces isolates yielded all four known and twelve new examples of the rare reveromycin class of polyketide spiroketals, including hemi-succinates, hemi-fumarates and hemi-furanoates. Reveromycins were identified with the aid of HPLC-DAD-MS and HPLC-DAD-SPE-NMR methodology, and structures were assigned by detailed spectroscopic analysis. The structural and mechanistic requirements for an unprecedented hemi-succinate : ketal-succinyl equilibrium were defined and provided a basis for proposing that reveromycin 4'-methyl esters and 5,6-spiroketals were artifacts. A plausible reveromycin polyketide biosynthesis is proposed, requiring a 2-methylsuccinyl-CoA starter unit, with flexible incorporation of a C(6-8) polyketide chain extension and diacid esterification units. Structure activity relationship investigations by co-metabolites were used to assess the anticancer, antibacterial and antifungal properties of reveromycins.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Leith
authors.initials: L
authors.lastname: Fremlin
authors.forename: Michelle
authors.initials: M
authors.lastname: Farrugia
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Piggott
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Khalil
authors.forename: Ernest
authors.initials: E
authors.lastname: Lacey
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Capon
mesh_terms: D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D013302:Streptomyces / Q000737:chemistry*
chemical_list: D001688:Biological Products; D005663:Furans; D011714:Pyrans; D013141:Spiro Compounds; C520774:spiroketal