FK-506, a novel immunosuppressant, has been isolated from the fermentation broth of Streptomyces tsukuhaensis No. 9993 as colorless prism and the molecular formula was determined as C44H69NOi2«H2O. The compoundsuppressed immuneresponses in vitro and in vivo with mice. This immunosuppressiveeffect was more potent than that of ciclosporin.Ciclosporin (CS), a fungal metabolite, is an effective immunosuppressant with low myelotoxicity0 and has been used successfully as the primary drug to suppress the rejection of transplants.2"0It is now well established that CS inhibits the production of T cell-derived soluble mediators such as interleukin 2 (IL-2), interleukin 3 (IL-3) and gamma-interferon (IFN-f) induced by antigens and lectins.5~8) The immunosuppressive agent which would attack specific target sites of cell are expected to provide a useful prototype o drugs for immunotherapy. Accordingly, we hav< tested a wide range of fermented broths fo specific inhibitory effects on IL-2 production. As a result, a strain of Streptomyces tsukuba ensis No. 9993 was found to produce the poten immunosuppressive agent, designated by th< code number of FK-506. Taxonomic study or this strain will be presented in a separate paper.9) In this paper, we describe the fermentation, isolation procedures and some chemical and biological properties of FK-506. As shown in Fig. 1, FK-506 is a neutral macrolide. Determination of the chemical structure of FK-506 will be published elsewhere.10) Materials and MethodsFermentati on A seed medium 100 ml containing glycerol 1 %, corn starch 1 %, glucose 0.5%, cotton seed meal 1 %, corn steep liquor 0.5% and calcium carbonate 0.2% at pH 6.5 was poured into a 500-ml Erlenmeyer flask and sterilized at 120°C for 30 minutes. A loopful of slant culture of S. tsukubaensis No.

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Many aspects of the nitrogen fixation process by photochemistry in the Titan atmosphere are not fully understood. The recent Cassini mission revealed organic aerosol formation in the upper atmosphere of Titan. It is not clear, however, how much and by what mechanism nitrogen is incorporated in Titan's organic aerosols. Using tunable synchrotron radiation at the Advanced Light Source, we demonstrate the first evidence of nitrogenated organic aerosol production by extreme ultraviolet-vacuum ultraviolet irradiation of a N 2 ∕CH 4 gas mixture. The ultrahigh-mass-resolution study with laser desorption ionization-Fourier transform-ion cyclotron resonance mass spectrometry of N 2 ∕CH 4 photolytic solid products at 60 and 82.5 nm indicates the predominance of highly nitrogenated compounds. The distinct nitrogen incorporations at the elemental abundances of H 2 C 2 N and HCN, respectively, are suggestive of important roles of H 2 C 2 N∕HCCN and HCN∕CN in their formation. The efficient formation of unsaturated hydrocarbons is observed in the gas phase without abundant nitrogenated neutrals at 60 nm, and this is confirmed by separately using 13 C and 15 N isotopically labeled initial gas mixtures. These observations strongly suggest a heterogeneous incorporation mechanism via short lived nitrogenated reactive species, such as HCCN radical, for nitrogenated organic aerosol formation, and imply that substantial amounts of nitrogen is fixed as organic macromolecular aerosols in Titan's atmosphere.