Nanaomycin

Discovery, producing organism and structure (1-6)

While screening for antibiotics more active against Mycoplasma gallisepticum than against bacteria, nanaomycins A, B, C, D and E were isolated from a culture broth of the actinomycete strain OS-3966. Nanaomycin A was found to possess potent inhibitory activity against fungi. The total syntheses of nanaomycins have been reported by many groups. The first total synthesis of nanaomycins A and D was reported by Li et al (7).

Physical data (Nanaomycin A)

Orange needles. C₁₆H₁₄O₆; mol wt 302.08. Sol. in MeOH, EtOH, CHCl₃, EtOAc.

Biosynthesis (3,8–11)

Nanaomycins are biosynthesized from eight acetate units via “polyketide” and are converted to D→A→E→B by enzymatic and non-enzymatic systems.

Biological activity (2,4,13,14)

1) Antimicrobial activity of nanaomycin A (2,4).

2) Therapeutic effect of nanaomycin A against Trichophyton mentagrophytes infection in guinea pigs (12)

3) Mode of action (13,14)
The quinone antibiotics, nanaomycins, are reduced by the respiratory chain-linked NADH or flavin dehydrogenase of the organism. The reduced forms of nanaomycins are quickly autooxidized by molecular oxygen producing O₂^—. The ability to produce O₂^— is related to the antimicrobial activity of nanaomycins.

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Nanaomycin is commercially available as an antifungal agent for animals.

References

1. [74] S. Ōmura et al., J. Antibiot., 27, 363–365 (1974)
2. [96] H. Tanaka et al., J. Antibiot., 28, 860–867 (1975)
3. [97] H. Tanaka et al., J. Antibiot., 28, 868–875 (1975)
4. [100] H. Tanaka et al., J. Antibiot., 28, 925–930 (1975)
5. [109] S. Ōmura et al., J. Chem. Soc., Chem. Commun., 320–321 (1976)
6. [157] M. Kasai et al., J. Antibiot., 32, 442–445 (1979)
7. T. T. Li et al., J. Am. Chem. Soc., 100, 6263–6265 (1978)
8. [184] C. Kitao et al., J. Antibiot., 33, 711–716 (1980)
9. [211] S. Ōmura et al., J. Biochem., 90, 291–293 (1981)
10. [212] S. Ōmura et al., J. Biochem., 90, 355–362 (1981)
11. [251] H. Tanaka et al., J. Antibiot., 35, 1565–1570 (1982)
12. [197] K. Kitaura et al., Jpn. J. Antibiot., 33, 728–732 (1980)
13. [196] H. Marumo et al., J. Antibiot., 33, 885–890 (1980)
14. [247] M. Hayashi et al., J. Antibiot., 35, 1078–1085 (1982)