Acremopeptin, a new peptaibol from Acremonium sp. PF1450

The inhibitor of apoptosis protein (IAP) plays important roles in cancer cells, apoptosis control, tumorgenesis and chemotherapy resistance.¹ The expression and function of IAP are deregulated in many human cancers because of genetic aberrations, an increase in their protein expression or the loss of endogenous inhibitors such as second mitochondria-derived activator of caspase (SMAC).² In cell cytoplasm, survivin, a member of IAP family, plays a role as a suppressor of apoptosis, together with X-chromosome-linked IAP (XIAP). Furthermore, survivin controls cell division by its association with Aurora B and inner centromere protein (INCENP). Because apoptosis induced by suppression of IAP can lead to antitumor effects, an IAP such as survivin is considered as a promising molecular target for cancer chemotherapy. YM155, a survivin suppressant, suppresses survivin expression through direct binding to its promoter,³ and induces regression of established human hormone-refractory prostate tumor xenografts.⁴ An SMAC-mimicking IAP antagonist, AT-406 binds to XIAP, c-IAP1 and c-IAP2, and prevents the association of these proteins with caspases and SMAC.⁵ An XIAP antisense oligonucleotide, AEG35156, efficiently decreases XIAP mRNA and XIAP protein amounts.⁶ In addition, their combination with other cytotoxic agents, small molecule signal transduction inhibitors, proteasome inhibitors and death receptor ligands potentiated their effects.²

Acremonium sp. PF1450 was isolated from a soil sample collected from Ishigaki Island in Okinawa prefecture, Japan. The strain was inoculated to 500-ml Erlenmeyer flasks each containing 100 ml of a medium comprising of 2% soluble starch, 1% glucose, 0.5% polypeptone (Nihon Seiyaku), 0.6% wheat germ, 0.3% yeast extract (Nihon Seiyaku), 0.2% soybean meal (Ajinomoto), 0.2% CaCO₃, with a pH of 7.0 before sterilization for seed culture. A loop of the slant culture of Acremonium sp. PF1450 was inoculated into 20 ml of the seed medium and was cultured on a rotary shaker at 25 °C for 3 days. Two ml of the seed cultured broth was transferred to 100 ml of the same medium and was cultured on a rotary shaker at 25 °C for 4 days.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD