title: Antibacterial Paramagnetic Quinones from Actinoallomurus.
abstract: Four metabolites, designated paramagnetoquinone A, B, C, and D (1-4), were isolated from three strains belonging to the actinomycete genus Actinoallomurus. Compounds 1 and 2 showed potent antibacterial activity with MIC values lower than 0.015 μg/mL against Gram-positive pathogens, including antibiotic-resistant strains. Since compounds 1 and 2 were NMR-silent due to the presence of an oxygen radical, structure elucidation was achieved through a combination of derivatizations, oxidations, and analysis of13C-labeled compounds. The paramagnetoquinones share the same carbon scaffold as tetracenomycin but carry two quinones and a five-membered lactone fused to the aromatic system. Compounds 2 and 1 are identical except for an unprecedented replacement of a methoxy in 2 by a methylamino group in 1. Related compounds devoid of methyl group(s) and of antibacterial activity were isolated from a different Actinoallomurus strain. The likely pmq biosynthetic gene cluster was identified from strain ID145113. While the cluster encodes many of the expected enzymes involved in the formation of aromatic polyketides, it also encodes a dedicated ketoacid dehydrogenase complex and an unusual acyl carrier protein transacylase, suggesting that an unusual starter unit might prime the polyketide synthase.
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Marianna
authors.identifier: 0000-0001-8669-5875
authors.initials: M
authors.lastname: Iorio
authors.affiliation: KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: João
authors.initials: J
authors.lastname: Cruz
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Simone
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Alice
authors.initials: A
authors.lastname: Bernasconi
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Brunati
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Sosio
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.|KtedoGen Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Donadio
authors.affiliation: Naicons Srl , Viale Ortles 22/4, 20139 Milano, Italy.
authors.forename: Sonia I
authors.initials: SI
authors.lastname: Maffioli
mesh_terms: D000192:Actinomycetales / Q000737:chemistry* / Q000235:genetics; D000213:Acyl Carrier Protein / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010802:Phylogeny; D048630:Polyketide Synthases / Q000378:metabolism; D061065:Polyketides; D011809:Quinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D000213:Acyl Carrier Protein; D000900:Anti-Bacterial Agents; D061065:Polyketides; D011809:Quinones; C000621510:paramagnetoquinone A; D048630:Polyketide Synthases