| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
In this research, the biosynthesis of NCS-chr core (DEDY) part was basically investigated. The analysis of composition of fatty acids derived from NCS producing F-41 strain was conducted. Iso-CィイD216:1ィエD2(ΔィイD19ィエD1) (10%-20% of total fatty acid fraction), a rare fatty acid, was detected by GC-MS, whereas the analysis of fatty acids composition derived from NCS unproducing F-41 strain iso-CィイD216:1ィエD2(ΔィイD19ィエD1) was negligible. In addition, total fatty acids fraction binding NA was isolated. But, it was impossible to purify this fatty acid fraction binding with NA to single compounds because this fraction was very labile as well as parent compound, NCS-chr.
The antitumor antibiotic neocarzinostatin composes of a protein and a non-protein chromophore (NCS-chr) at a molar ratio 1:1. This very labile NCS-chr is responsible for the biological activities of the parent compound. The chemical structure of this chromophore was elucidated as a bicyclo [7, 3, 0] dodecadienediyne (DEDY) system
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having 2-hydroxy-7-methxy-5-methyl-1-naphthalenecarboxylic acid (NA), N-methylfucosamine (MF), ethylene carbonate (EC) and high strained epoxide (SE).
The biosynthetic pathway of NCS-chr was reported on the basis of the incorporation of the ィイD113ィエD1C labeled acetate precursors by Hensens. The acetate incorporation results suggested that the NA was derived from a hexaketide and DEDY ring system from a oleate or creptenyate.
Above observations, it is suggested that the key compound of the biosynthetic pathway of NCS-chr was very labile unsaturated fatty acid having a NA moiety. And it can be presumed that after this unsaturated fatty acid coupled with MF, and then both SE and EC moieties might introduce to this fatty acid by epoxidation and carbonation, respectively.
In addition, squalene, dehydrosqualene, tetrahydrosualene, diploptene was isolated and bactriohopanes were detected in organic solvent extract of F-41 strain. But, the role of these squalenes and hopanoids concerning NCS-chr biosynthesis is now unclear Less
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