Easter Island, rapamycin from

Rapamycin is a macrocyclic lactone produced by Streptomyces hygroscopious. This bacterium was originally cultured from a soil sample collected on Easter Island (known locally as Rapa Nui hence the name rapamycin). Parenthetically, rapamycin shares an interesting mode of action with two other antifungal and immunosuppressive compounds, FK506and cyclosporin A. Inside cells, rapamycin first binds to FKBP12, a small protein receptor known as an immunophilin. FKBP12 is not an essential protein but is an important cofactor required for rapamycin to bind and inhibit TOR. 

Rapamycin (sirolimus) is another macrolide antibiotic that possesses potent immunosuppressant activity. Rapamycin has a chemical structure partially similar to that of tacrolimus (Fig. 2). It was first isolated from Streptomyces hygro-scopicus strains found in soil obtained on Rapa Nui (Easter Island), hence the name rapamycin [19, 20]. This compound was initially investigated as an antifungal agent and later found to have immunosuppressive activity [21]. Rapamycin also binds to FKBP, but its immunosuppressive mechanisms are distinct from those of tacrolimus and cyclosporin in that it does not act via the calcineurin pathway [22, 23]. The immunosuppressive effects of rapamycin result from its inhibition of T-cell [23, 24] and B-cell [25] proliferation. The key effect on those cells results from the blocking of the signals of several cytokines (IL-2 and IL-4), leading to interruption of the cell cycle from the G, to the S phase. Unlike tacrolimus, the complex of rapamycin and FKBP-12 does not inhibit the dephosphorylase... 

The rapamycin-producing streptomycete strain AY B-994 isolated from Easter Island (Rapa Nui) soil was first grown on yeast-starch agar (12). The organism was identified as... 

As noted in the Chapter 5 Lagniappe, more than half of all new drug candidates come either directly or indirectly from natural products. All four natural products shown in the introduction to this chapter, for instance, are used as drugs morphine from the opium poppy, prostaglandin Ej from sheep prostate glands, erythromycin A from a Strepto-myces erythreus bacterium cultured from a Philippine soil sample, and benzylpenicillin from Penicillium nota-tum. Still other examples include rapamycin (Figure 25.15), an immunosuppressant isolated from a Strepto-myceshygroscopicus bacterium first found in a soil sample from Easter Island (Rapa Nui), and paclitaxel (Taxol),... 

Rapamycin, an immunosuppressant natural product used during organ transplants, was originally isolated from a soil sample found on Easter Island, or Rapa Nui, an island 2200 miles offthe coast of Chile known for its giant Moai statues. 

---