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.

A new enzyme involved in the control of the stereochemistry in the decalin formation during equisetin biosynthesis

“…pyrrolocin B and C, were produced in a heterologous expression host that carries prlS and prlC [16,17]. This observation is consistent with our findings and strongly supports the idea that Fsa2 is a new enzyme involved in the stereoselective formation of the decalin ring of 1.…”

“…These correlations also assigned the configurations of C-2 of 3, which were same as those of 1. The optical rotation ([a] 589 24 þ158 ) and the CD spectrum and C, showed a similar change in the measurement of optical rotation and CD spectra [16]. These observations suggested that the absolute configuration for the decalin moiety of 3 was 2S, 3S, 6R, 8R, 11R, and 5 0 S. Therefore, fsa2 is responsible for the stereocontrol at C-3 and C-6 positions among the stereocenters forged in the [4þ2] cycloaddition, i.e., it functions as an endo-selective Diels-Alderase in the decalin formation of 1 (Fig.…”

Hyalodendrins A and B, New Decalin-Type Tetramic Acid Larvicides from the Endophytic Fungus Hyalodendriella sp. Ponipodef12

“…It seems that the configuration at C-5 has strong correlation with the larvicidal activities, as the epimer of 1 (i.e., 2) was two times less active than that of 1. Decalin-type tetramic acid metabolites were found to display diverse activities, such as HIV-1 integrase inhibiting activity [19], antibacterial activity [18,[20][21][22], antimalarial activity [23] and anti-parasite activity against Trichomonas vaginalis [24]. Our research revealed these type of compounds also have larvicidal function.…”

Zosteropenillines: Polyketides from the Marine-Derived Fungus Penicillium thomii

“…Polyketides containing “decalin” moiety exhibit diverse biological properties such as anticancer, antimicrobial, neurotrophic, and growth-stimulating activity [23,24,25,26,27]. Twelve new polyketides, named zosteropenillines A–L ( 1 – 12 ), have been isolated from the extract of the marine-derived fungus Penicillium thomii .…”