Discovery of a Fungal Multicopper Oxidase That Catalyzes the Regioselective Coupling of a Tricyclic Naphthopyranone To Produce Atropisomers.

Atropisomeric dinapinones A1 and A2 (DPA1 and DPA2) were isolated from a culture of Talaromyces pinophilus FKI-3864. Monapinone coupling enzyme (MCE), which dimerizes naphthopyranone monapinone A (MPA), was purified from a cell-free extract of T. pinophilus FKI-3864.

Structure-Activity Analysis of Gram-positive Bacterium-producing Lasso Peptides with Anti-mycobacterial Activity.

Lariatin A, an 18-residue lasso peptide encoded by the five-gene cluster larABCDE, displays potent and selective anti-mycobacterial activity. The structural feature is an N-terminal macrolactam ring, through which the C-terminal passed to form the rigid lariat-protoknot structure. In the present study, we established a convergent expression system by the strategy in which larA mutant gene-carrying plasmids were transformed into larA-deficient Rhodococcus jostii, and generated 36 lariatin variants of the precursor protein LarA to investigate the biosynthesis and the structure-activity relationships.

Inhibition of bacterial undecaprenyl pyrophosphate synthase by small fungal molecules.

Viridicatumtoxin and spirohexaline, small fungal molecules with a tetracyclic scaffold and an additional spirobicyclic ring in common, were found to inhibit bacterial undecaprenyl pyrophosphate (UPP) synthase with IC values of 4 and 9 μm, respectively. These molecules showed weak inhibitory activity against catalytically related enzymes such as bacterial octaprenyl pyrophosphate synthase and yeast dehydrodolichyl pyrophosphate synthase, indicating that the compounds preferentially inhibit UPP synthase. They showed antimicrobial activity, particularly against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA).

Epi-trichosetin, a new undecaprenyl pyrophosphate synthase inhibitor, produced by Fusarium oxysporum FKI-4553.

A new compound, designated epi-trichosetin (1), was isolated along with the known compound trichosetin (2) from the culture broth of Fusarium oxysporum FKI-4553 by solvent extraction, silica gel column chromatography and reversed-phase HPLC. The structure of 1 was elucidated by comparing various spectral data with those of 2, revealing that 1 was a stereoisomer of 2. Compounds 1 and 2 inhibited the undecaprenyl pyrophosphate synthase activity of Staphylococcus aureus with IC50 values of 83 and 30 μM, respectively, and showed antimicrobial activity, particularly against Gram-positive bacteria, including methicillin-sensitive and -resistant S.

Anti-infectious agents against MRSA.

Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA) has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652) targeting MRSA cell wall biosynthesis have been discovered using unique screening methods.