title: Isolation of pyrrolocins A-C: cis- and trans-decalin tetramic acid antibiotics from an endophytic fungal-derived pathway.
abstract: Three new decalin-type tetramic acid analogues, pyrrolocins A (1), B (2), and C (3), were defined as products of a metabolic pathway from a fern endophyte, NRRL 50135, from Papua New Guinea. NRRL 50135 initially produced 1 but ceased its production before chemical or biological evaluation could be completed. Upon transfer of the biosynthetic pathway to a model host, 1-3 were produced. All three compounds are structurally related to equisetin-type compounds, with 1 and 3 having a trans-decalin ring system, while 2 has a cis-fused decalin. All were active against Mycobacterium tuberculosis, with the trans-decalin analogues 1 and 3 exhibiting lower MICs than the cis-decalin analogue 2. Here we report the isolation, structure elucidation, and antimycobacterial activities of 1-3 from the recombinant expression as well as the isolation of 1 from the wild-type fungus NRRL 50135.
authors.affiliation: Department of Pharmacology and Toxicology, ‡Department of Medicinal Chemistry, and ΔCenter for High Performance Computing, University of Utah , Salt Lake City, Utah United States.
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Jadulco
authors.forename: Michael
authors.initials: M
authors.lastname: Koch
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kakule
authors.forename: Eric W
authors.initials: EW
authors.lastname: Schmidt
authors.forename: Anita
authors.initials: A
authors.lastname: Orendt
authors.forename: Haiyin
authors.initials: H
authors.lastname: He
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Janso
authors.forename: Guy T
authors.initials: GT
authors.lastname: Carter
authors.forename: Erica C
authors.initials: EC
authors.lastname: Larson
authors.forename: Christopher
authors.initials: C
authors.lastname: Pond
authors.forename: Teatulohi K
authors.initials: TK
authors.lastname: Matainaho
authors.forename: Louis R
authors.initials: LR
authors.lastname: Barrows
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D060026:Endophytes / Q000737:chemistry*; D029624:Ferns / Q000382:microbiology*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D009281:Naphthalenes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D010219:Papua New Guinea; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013237:Stereoisomerism; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013764:Tetrahydronaphthalenes / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D009281:Naphthalenes; D011760:Pyrrolidinones; D013764:Tetrahydronaphthalenes; C000599241:pyrrolocin A; C000599243:pyrrolocin B; C000599242:pyrrolocin C; C009435:tetramic acid; C024509:equisetin; C007229:decalin