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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Anti-Bacterial Agents / chemistry
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Anti-Bacterial Agents / isolation & purification*
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Anti-Bacterial Agents / pharmacology*
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Bacillus subtilis / drug effects
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Endophytes / chemistry*
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Ferns / microbiology*
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Microbial Sensitivity Tests
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Models, Molecular
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Molecular Structure
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Mycobacterium tuberculosis / drug effects
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Naphthalenes / chemistry
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Nuclear Magnetic Resonance, Biomolecular
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Papua New Guinea
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Pyrrolidinones / chemistry
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Pyrrolidinones / isolation & purification*
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Pyrrolidinones / pharmacology*
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Staphylococcus aureus / drug effects
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Stereoisomerism
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Streptococcus pneumoniae / drug effects
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Tetrahydronaphthalenes / chemistry
Substances
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Anti-Bacterial Agents
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Naphthalenes
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Pyrrolidinones
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Tetrahydronaphthalenes
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pyrrolocin A
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pyrrolocin B
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pyrrolocin C
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tetramic acid
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equisetin
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decalin