Novel fungal diphenyl ether biosynthetic gene clusters encode a promiscuous oxidase for elevated antibacterial activities.

Diphenyl ethers (DPEs) are produced by filamentous fungi using polyketide synthases (PKSs) directly, or via Cu oxidase-catalyzed oxidative rearrangements of benzophenone intermediates. Here, we use heterologous expression to reveal a third route towards DPEs in Preussia isomera that relies on an oxidative multienzyme cascade to convert a PKS-generated, ester-linked didepside to depsidones and further to DPEs, and apply comparative genomics to identify conserved biosynthetic gene clusters for this pathway in multiple fungi. The distribution of DPE products is modulated by the expression chassis upon pathway reconstitution. Among the post-PKS enzymes, the DpeH tyrosinase shows considerable substrate promiscuity towards synthetic DPE analogues. By creating hybrid enzymes with a DpeH orthologue from Aspergillus nidulans, we identify the C-terminal region of DpeH to alter substrate recognition. Our work highlights an evolutionarily conserved way to produce DPEs, and provides enzymatic tools to generate DPE analogues with broad spectrum antibiotic activity against multidrug-resistant human pathogens.

Emerindanols A and B: Two Bipolyhydroindenol Sesterterpenes with 5/6-6/5 Coupled Ring System Discovered by Genome Mining.

Genome mining of Emericella sp. XL-029 achieved a new type E sesterterpene synthase, EmES, which affored a novel bipolyhydroindenol sesterterpene, emerindanol A. Heterologous coexpression with the upstream P450 oxidase revealed C-4 hydroxylated product, emerindanol B. Notably, emerindanols A and B represented the first sesterterpenes featuring a unique 5/6-6/5 coupled ring system. EmES was postulated to initiate through C1-IV-V pathway and convert the fused ring intermediate into the final coupled ring product through a spiro skeleton.

Chae-type cytochalasans from coculture of Aspergillus flavipes and Chaetomium globosum.

Cocultivation of the high cytochalasan-producing fungi Aspergillus flavipes and Chaetomium globosum resulted in the isolation of 11 undescribed Chae-type cytochalasans. Their structures were determined by spectroscopic data and NMR data calculations. Asperchaetoglobin A (1) was the first Chae-type cytochalasan possessing an unprecedented nitrogen bridge between C-17 and C-20 to generate a surprising 5/6/12/5 multiple ring system; asperchaetoglobins B and C (2 and 3) displayed higher oxidation with an additional epoxide at the thirteen-member ring; asperchaetoglobin D (4) was the second Chae-type cytochalasin featuring a 5/6/12 tricyclic ring system. The cytotoxic activities against five human cancer cell lines and antibacterial activities against Staphylococcus aureus and Colon bacillus of selected compounds were evaluated in vitro.

Two new quinazoline alkaloids produced by Aspergillus versicolor and their antimicrobial activities.

Two new quinazoline alkaloids versicomides G-H (1 and 2), together with seven known compounds, were isolated from Aspergillus versicolor HYQZ-215 obtained from the sediment of Qarhan Salt Lake. Their structures were elucidated by NMR, HRESIMS, and quantum chemical ECD calculations data. The antimicrobial activities of these compounds were evaluated against seven agricultural pathogenic fungi and eight clinically drug-resistant bacteria.

Thiazolo[5,4-b]pyridine Alkaloid and Seven ar-Bisabol Sesquiterpenes Produced by the Endophytic Fungus Penicillium janthinellum.

We investigated the secondary metabolites present in Penicillium janthinellum MPT-25, an endophytic fungus isolated from Taxus wallichiana var. chinensis (Pilger) Florin. Chemical characterization of the solid cultured extract resulted in the isolation of 11 compounds, including eight previously undescribed metabolites: a thiazolo[5,4-b]pyridine alkaloid, janthinedine A (1), and seven ar-bisabol sesquiterpenes, janthinepenes A-G (2-8). Their structures were elucidated by a combination of extensive spectroscopic methods, including single-crystal X-ray diffraction and ECD spectra. The antimicrobial activities of these compounds were evaluated against seven agricultural pathogenic fungi and eight clinically drug-resistant bacteria.

New chromone analog and pyrrole alkaloid produced by Penicillium sclerotiorum and their antibacterial activity.

A new chromone analog (1) and a new pyrrole alkaloid (2), together with four known compounds, were isolated from the endophytic fungus Penicillium sclerotiorum MPT-250 obtained from the stems of Taxus wallichiana var. chinensis (Pilger) Florin. The structural elucidation of these metabolites was performed by high-resolution mass spectrometry and NMR spectroscopy. Compounds 1 and 5 exhibited significant antibacterial activity against carbapenems-resistant Pseudomonas aeruginosa and multidrug-resistant Enterococcus faecium with an minimum inhibitory concentration (MIC) value of 3.13 µg/ml respectively.

Synthesis of Multicolor Carbon Dots Based on Solvent Control and Its Application in the Detection of Crystal Violet.

The adjustment of the emitting wavelength of carbon dots (CDs) is usually realized by changing the raw materials, reaction temperature, or time. This paper reported the effective synthesis of multicolor photoluminescent CDs only by changing the solvent in a one-step solvothermal method, with 1,2,4,5-tetraaminobenzene as both the novel carbon source and nitrogen source. The emission wavelengths of the as-prepared CDs ranged from 527 to 605 nm, with quantum yields (QYs) reaching 10.0% to 47.6%, and it was successfully employed as fluorescence ink. The prepared red-emitting CDs (R-CDs, λem = 605 nm) and yellow-emitting CDs (Y-CDs, λem = 543 nm) were compared through multiple characterization methods, and their luminescence mechanism was studied. It was discovered that the large particle size, the existence of graphite Ns, and oxygen-containing functional groups are beneficial to the formation of long wavelength-emitting CDs. Y-CDs responded to crystal violet, and its fluorescence could be quenched. This phenomenon was thus employed to develop a detection method for crystal violet with a linear range from 0.1 to 11 µM and a detection limit of 20 nM.