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. 2018 Jul 27:6:314.
doi: 10.3389/fchem.2018.00314. eCollection 2018.

Brasilianoids A-F, New Meroterpenoids From the Sponge-Associated Fungus Penicillium brasilianum

Affiliations

Brasilianoids A-F, New Meroterpenoids From the Sponge-Associated Fungus Penicillium brasilianum

Jianping Zhang et al. Front Chem. .

Abstract

3,5-Dimethylorsellinic acid (DMOA) derived meroterpenoids comprise an unique class of natural products with diverse scaffolds and with a broad spectrum of bioactivities. Bioinformatics analysis of the gene clusters in association with the qRT-PCR detection of the amplification of two key genes led to speculate that the sponge associated fungus Penicillium brasilianum WZXY-m122-9 is a potential producer of meroterpenoids. Chromatographic separation of the EtOAc extract of this fungal strain on a large-scale fermentation resulted in the isolation of six new DMOA-related meroterpenoids with trivial names of brasilianoids A-F (1-6), together with preaustinoid D and preaustinoid A2. The structures were determined by extensive analyses of spectroscopic data, including the X-ray diffraction and the ECD data for configurational assignment. Brasilianoids A and F showed an unprecedented skeleton with a γ-lactone in ring A, while brasilianoids B-C featured a 7/6/6/5/5 pentacyclic ring system finding in nature for the first time. The biosynthetic relationship among the isolated compounds was postulated. Compound 1 significantly stimulated the expression of filaggrin and caspase-14 in HaCaT cells in dose-dependent manner, while compounds 2 and 3 showed moderate inhibition against NO production in LPS-induced RAW 264.7 macrophages.

Keywords: Penicillium brasilianum; brasilianoids A–F; inhibition of NO production; sponge-associated fungus; stimulation of filaggrin and caspase-14.

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Figures

Figure 1
Figure 1
Comparison of the gene clusters between P. brasilianum WZXY-m122-9 and P. brasilianum MG11. (A) Comparison of the genes in cluster A of P. brasilianum WZXY-m122-9 with the aus's genes (cluster A) from P. brasilianum MG11. The homologous genes between the gene clusters were linked with lines. (B) Comparison of the genes in cluster B of P. brasilianum WZXY-m122-9 with the aus's genes (cluster B) from P. brasilianum MG11. The homologous genes between the gene clusters were linked with lines. PM-122-9-5653 and others mean the genes in P. brasilianum WZXY-m122-9.
Figure 2
Figure 2
Structures of 1–8.
Figure 3
Figure 3
Key NOE correlations of 1–3 and 6. Arrow line means the NOE correlation from one proton to the other proton.
Figure 4
Figure 4
Experimental and calculated ECD of 1, 6, and 7.
Figure 5
Figure 5
X-ray crystallographic structures of 2-5.
Figure 6
Figure 6
Upregulation of caspase 14 and filaggrin in HaCaT cells induced by 1 1% DMSO for the dissolution of compounds is used as the control. The vertical axis represents the expression of caspase-14 (A) and filaggrin (B) in HaCaT cells, and the horizontal axis means the doses of compound 1. Statistical significances were considered at the *P < 0.05 and **P < 0.01 levels.
Scheme 1
Scheme 1
Proposal of putative biosynthetic pathways for the compounds.

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