Discovery, Biosynthesis, and Heterologous Production of Streptoseomycin, an Anti-Microaerophilic Bacteria Macrodilactone.

Streptoseomycin (1), which is a rare macrodilactone with potent activities against microaerophilic bacteria, featuring a pentacyclic 5/14/10/6/6 ring system together with an ether bridge, was characterized by a combination of spectroscopic method and X-ray analysis from a marine Streptomyces seoulensis. Sequencing and characterization of a ∼76-kb biosynthetic gene cluster led to the proposition of the biosynthetic pathway of 1. Heterologous expression of the gene cluster using a BAC vector in Streptomyces chartreusis 1018 led to the successful production of 1.

New Antibacterial Phenone Derivatives Asperphenone A-C from Mangrove-Derived Fungus Aspergillus sp. YHZ-1.

Marine fungi are a promising source of novel bioactive natural products with diverse structure. In our search for new bioactive natural products from marine fungi, three new phenone derivatives, asperphenone A-C (1-3), have been isolated from the ethyl acetate extract of the fermentation broth of the mangrove-derived fungus, Aspergillus sp. YHZ-1. The chemical structures of these natural products were elucidated on the basis of mass spectrometry, one- and two-dimensional NMR spectroscopic analysis and asperphenone A and B were confirmed by single-crystal X-ray crystallography. Compounds 1 and 2 exhibited weak antibacterial activity against four Gram-positive bacteria, Staphylococcus aureus CMCC(B) 26003, Streptococcus pyogenes ATCC19615, Bacillus subtilis CICC 10283 and Micrococcus luteus, with the MIC values higher than 32.0 µM.

Novel chaetospirolactone and orsellide F from an endophytic fungus Chaetomium sp.

Chaetospirolactone (1), a novel spiro-lactone bearing a rare 1-oxaspiro [4.4] non-7-ene-2,6-dione skeleton, and orsellide F (2), together with six known compounds (3-8), were isolated from an endophytic fungus Chaetomium sp. NF00754. Their structures were determined by interpretation of spectroscopic data. The absolute configurations of 1 and 2 were established by analysis of single X-ray crystallographic data and CD spectra. Compounds 3, 4, and 6 showed moderate acetylcholinesterase inhibitory activity with IC50 values of 7.34, 5.19, and 7.67 µM, respectively.

Rifamorpholines A-E, potential antibiotics from locust-associated actinobacteria Amycolatopsis sp. Hca4.

Cultivation of locust associated rare actinobacteria, Amycolatopsis sp. HCa4, has provided five unusual macrolactams rifamorpholines A-E. Their structures were determined by interpretation of spectroscopic and crystallographic data. Rifamorpholines A-E possess an unprecedented 5/6/6/6 ring chromophore, representing a new subclass of rifamycin antibiotics. The biosynthetic pathway for compounds 1-5 involves a key 1,6-cyclization for the formation of the morpholine ring. Compounds 2 and 4 showed potent activities against methicillin-resistant Staphylococcus aureus (MRSA) with MICs of 4.0 and 8.0 µM, respectively.

Visible-light-promoted synthesis of phenanthridines via an intermolecular isocyanide insertion reaction.

An isocyanide insertion reaction promoted by the combination of an amide and a photoredox is now presented. By using visible light, 6-amidophenanthridine derivatives can be prepared in good chemical yields under mild and eco-friendly reaction conditions. The reaction was shown to proceed through an electron transfer sequence by mechanistic experiments, and thus enabled the efficient production of 24 compounds, each with one new intramolecular aromatic ring obtained. The synthesized compounds were tested to embody good antitumor, antimicrobial and neuraminidase inhibitory activities.

Herpecaudin from Herpetospermum caudigerum, a Xanthine Oxidase Inhibitor with a Novel Isoprenoid Scaffold.

Herpecaudin (3), a xanthine oxidase inhibitor with an unprecedented scaffold, was discovered from Herpetospermum caudigerum seeds. The structure was determined by spectroscopic and X-ray single crystallographic methods. A possible biogenetic pathway leading to herpecaudin is proposed, starting from congeners 23,24-dihydrocucurbitacin E (1) and endecaphyllacin B (2), and involving retro-aldol cleavage as a key step. All three compounds proved to be active and represent new scaffolds of non-purine analogue xanthine oxidase inhibitors.

Curindolizine, an Anti-Inflammatory Agent Assembled via Michael Addition of Pyrrole Alkaloids Inside Fungal Cells.

Curvularia sp. IFB-Z10, a white croaker-associated fungus, generates a skeletally unprecedented indolizine alkaloid named curindolizine (1), which displays an anti-inflammatory action in lipopolyssacharide (LPS)-induced RAW 264.7 macrophages with an IC50 value of 5.31 ± 0.21 µM. The enzymatic transformation test demonstrated that the unique curindolizine architecture was most likely produced by the regiospecific in-cell Michael addition reaction between pyrrole alkaloids, curvulamine, and 3,5-dimethylindolizin-8(5H)-one.

Muta-mycosynthesis of naphthalene analogs.

A mutasynthetic strategy is introduced for the mycosynthesis of naphthalene-based molecules (mutadalesols A-F) with directed substitution patterns and new frameworks by generating and using the ΔpksTL mutant strain of Daldinia eschscholzii. (±)-Mutadalesol A and its (+)-enantiomer are cytotoxic, and its (-)-enantiomer inhibits Toll-like receptor 5 (TLR5). The in-culture reactability of fungal oligoketide intermediates with 5-aminonaphthalen-1-ol (ANL) is demonstrated, shedding light on bioorthogonal accesses to unnatural molecule libraries valuable in drug discovery pipelines.