A variety of growth factors and cytokines control proliferation and differentiation and cell survival in various types of cells by regulating gene expression. Transforming growth factor-β (TGF-β), first discovered as a trophic factor for several different cell lines,1} is nowwell known to act as a growth inhibitor against various kinds of mammalian cells2). The mode of action of TGF-β is not fully understood but it is known to induce expression of a variety of genes such as a tumor suppression gene p21, plasminogen activator inhibitor-1 (PAI-1), to suppress tumor progression. Transfection with a TGF-β type II receptor gene into SW48 colon cancer cells, which lack functional cell surface TGF-β type II receptors, restores the susceptibility to growth inhibition by TGF-β and reverses the in vitro and in vivo malignant phenotype3). In addition, the restoration of TGF-β signaling in LNCaP human prostate cancer cells suppresses tumorigenicity with inducing apoptosis4). Thus, substances which mimic the gene expression-enhancing activity of TGF-β are expected to be useful chemotherapeutic agents for cancer treatment. In order to detect the gene expression ability of TGF-β, we constructed an assay system utilizing the expression of a reporter gene. MvlLu mink lung epithelial cells express TGF-β receptors abundantly and respond to TGF-β resulting in the expression of plasminogen activator inhibitor-1 (PAI-1)5). The cells were transfected with aplasmid bearing the firefly luciferase reporter gene inserted downstream of PAI-1 promoter6). Thus microbial samples with TGF-β-like activity can be detected by the production of luciferase which is measured with a luminometer. During the course of our screening using this system, we isolated histone deacetylase inhibitors such as trichostatin A7)8) and diheteropeptin9). Further investigation has resulted in the isolation of a new metabolite with gene expressionenhancing activity, phoenistatin (1, Fig. 1). We report herein the production, isolation and structure determination ofl.