A potent tyrosine kinase inhibitor, lavendustin A [1], has been isolated from a butyl acetate extract of Streptomyces griseolavendus culture filtrate. It inhibits epidermal growth factor receptor-associated tyrosine kinase with an IC50 of 4.4 ng/ml, which is about 50 times more inhibitory than erbstatin. It does not inhibit protein kinase A or C. Its structure, determined by spectral data and total synthesis, is novel, having a tertiary amine in the center with substituted benzyl and phenyl groups. Lavendustin A competes with ATP and is noncompetitive with the peptide. Its structure-activity relationship is discussed.

Screening for inhibitors of the ubiquitin-proteasome pathway, considered to regulate important cellular events and linked to serious diseases as well, led to isolation of a new compound, panepophenanthrin, from the fermented broth of a mushroom strain, Panus rudis Fr. IFO 8994. This is the first inhibitor of the ubiquitin-activating enzyme, which is indispensable for the ubiquitin-proteasome pathway. The structure of panepophenanthrin was determined by NMR and X-ray crystallographic analyses as 1,3a,10-trihydroxy-10c-(3-hydroxy-3-methylbut-1-enyl)-5,5-dimethyl-1,2,3,3a,5,5a,8,9,10,10a,10b,10c-dodecahydro-4-oxa-2,3,8,9-diepoxyacephenanthrylen-7-one.

The absolute structure of a new antibiotic lactonamycin is described. The NMRstudies deduced one of four possible structures for the aglycon attached by a rhodinose through glycosidic bond. The stereochemistry of the sugar obtained by an acid hydrolysis was determined to be L-form by measuring optical rotation. The stereochemistry of the aglycon was determined by X-ray crystallographic analysis.Lactonamycin 1 has been isolated from a culture broth

Cultured broths were screened by measuring the inhibition of monoamine oxidase. Using serotonin as the substrate, two active agents were isolated from Actinomycetes and shown to be pimprinine and trans-cmnsjmc acid amide, and a compoundisolated from a mushroomwas identified to be harman. Using benzylamine as the substrate, an inhibitor was isolated from a Streptomyces and shown to be phenethylamine.

Since the multiple drug resistance of MRSAis still expanding, new anti-MRSA drugs with different structures and activities have to be sought. Amythiamicin A, B, C and D, new members of the cyclic thiazolyl peptide family, were isolated for their effectiveness against MRSA1^. Looking for possible molecular targets for future anti-MRSA drugs, we attempted to elucidate the mechanismof action of amythiamicins.Cyclic thiazolyl peptide antibiotics, such as thiostrepton, siomicin, thiopeptin, and sporangiomycin are all known