Chemical diversity from the Tibetan Plateau fungi Penicillium kongii and P. brasilianum

Abstract

Two new secondary metabolites, kongiilines A and B (1, 7), and two asperphenamate derivatives, asperphenamates B and C (5–6), together with 16 known compounds (2–4, 8–20), were isolated from Tibetan Plateau fungi Penicillium kongii and Penicillium brasilianum. This is the first report on asperphenamates B and C as naturally occurring compounds, and that aspterric acid is isolated from P. brasilianum for the first time. Their structures were elucidated by different spectroscopic techniques including high-resolution electrospray ionisation mass spectrum, 1D nuclear magnetic resonance (NMR), and 2D NMR as well as electronic circular dichroism. Compounds 4, 5, and 10 exhibited cytotoxicity activities against human colon carcinoma HCT116 cell line with IC50 values of 88.16, 77.68, and 36.92 μM, respectively. Fungi from Tibetan Plateau represent important and rich resources for the investigation of new chemicals.

Mass Spectrometry Guided Discovery and Design of Novel Asperphenamate Analogs From Penicillium astrolabium Reveals an Extraordinary NRPS Flexibility

“…Moreover, asperphenidine F1, was the only active candidate against the pancreas cell line, suggesting the nicotinic acid analogs being more active than the benzoic acid analogs. Although our cytotoxicity results for asperphenamates F and Y, as well as asperphenidine F1 are comparable to the previously published data, none of them show improved bioactivity compared to synthetic asperphenamate derivatives ( Li et al, 2012 ; Yuan et al, 2012 , 2018 , 2019 , 2020 ; Liu et al, 2016 , 2018 ).…”

“…1 H and 13 C NMR data shown in Table 1, with full assignment table and spectra available in supplementary material (Supplementary Tables 2-4 and Supplementary Figures 1-5). Data for asperphenamate (1) and the tyrosine analog (4) fit with previously published data (Catalán et al, 2003;Liu et al, 2018). 1 H and 13 C NMR shifts of N-benzoylphenylalaninol and the N-benzoyl part of non-reduced AA moiety was in agreement within all four compounds, further supported by COSY and HMBC correlations for tryptophan (12) and leucine (13) analogs (Figure 5 and Supplementary Tables 3-4).…”

“…Although asperphenamate is mainly known for its antitumour activity and immense synthetic chemists interest in asperphenamate backbone modification ( Li et al, 2012 ; Yuan et al, 2012 , 2018 , 2019 , 2020 ; Liu et al, 2016 ), recent studies have also shown asperphenamate to be a potential neuroinflamatory inhibitor ( Zhou et al, 2017 ), and to possess anti-HIV ( Bunteang et al, 2018 ) and antidiabetic ( Del Valle et al, 2016 ) properties. In recent years, a handful of new natural analogs have been isolated, namely Asperphenamates B ( 4 ) and C ( 5 ) ( Liu et al, 2018 ), and 4-OMe-asperphenamate ( Zheng et al, 2013 ; Ratnaweera et al, 2016 ) ( 6 ) from filamentous fungi. Other analogs containing partial structural similarities include: patriscabratine ( 7 ), a N-benzoylphenylalanine phenylalanynol acetate ester, aurantiamide ( 8 ) and aurantiamide acetate ( 9 ) ( Zhou et al, 2017 ), N-benzoylphenylalanine phenylalanynol and phenylalanynol acetate amides, all isolated from plant material; cordyceamides A ( 10 ) and B ( 11 ) ( Jia et al, 2009 ), a N-benzoyl-L-tyrosinyl-L-phenylalaninol and N-benzoyl-L-tyrosinyl-L- p -hydroxyphenylalaninol acetates, from an insect pathogen fungus ( Figure 1 ); along with a number of tentatively identified related metabolites ( Kildgaard et al, 2014 ; Sica et al, 2016 ).…”

Highlighting the Biotechnological Potential of Deep Oceanic Crust Fungi through the Prism of Their Antimicrobial Activity

“…Asperphenidine is an analogue constituted by phenylalanine and nicotinic acid ( Figure 5 ). Recently, some new natural asperphenamate analogues have been isolated from several fungi, such as 4-OMe-asperphenamate [ 48 , 52 ] and asperphenamates B and C [ 53 ]. Moreover, 22 new asperphenamate analogues were isolated from Penicillium astrolabium and assigned by HRMS/MS.…”

Mining the Metabolome and the Agricultural and Pharmaceutical Potential of Sea Foam-Derived Fungi

“…A total of 18 annotated compound classes included some known mycotoxins of Penicillium spp., such as the meroterpenoid mycophenolic acid [13] and the cyclic tetrapeptide fungisporin [14] ( Figure 3A). Others included the meroterpenoids andrastin A [15] and prestaunoid A1 [16], polyketides italicic acid [17], xanthoepocin [18], rubratoxin B [19] and canadensolide [20], indole alkaloids brevianamide A [21], communesin G [22] and fumiquinazoline A [23], diketopiperazine roquefortine C [24], phenylalanine derivative asperphenamate [25], tropolone viticolin C [26], pentacyclic alkaloid citrinadin A [27] Another MF shared by all three Penicillium strains was the fungisporin cluster ( Figure 3A). The cyclic tetrapeptide fungisporin (only identified in Penicillium isolate 62.72 F1A) was also annotated based on the molecular formula prediction from HRMS m/z [M + H] + 493.2815 (C28H37N4O4, 0.6 ppm error) and MS/MS similarity to that published in the literature [14].…”