Azinomycin B Explained

Azinomycin B is a natural product that contains densely assembled functionalities with potent antitumor activity.^[1] It is isolated from Streptomyces sahachiroi^[2] which is reisolated from S. griseofuscus along with its analog azinomycin A.^[3] Azinomycin B can bind within the major groove of DNA and forms covalent interstrand crosslinks (ISCs) with the purine bases.^{[4] [5] [6] [7]} The DNA alkylation and crosslinking by azinomycin B suggests its potent antitumor activity.^[8]

Biosynthesis

The biosynthesis of azinomycin B includes a type 1 polyketide synthase and several nonribosomal peptide synthetases.^[9]

Notes and References

1. Zhao, Qunfei, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, and Wen Liu. "Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis." Chemistry & Biology 15.7 (2008): 693-705. Web.
2. Hata, T., Koga, F., Sano, Y., Kanamori, K., Matsumae, A., Sunagawa, R., Hoshi, T., Shima, T., Ito, S., and Tomizawa, S. (1954). Carzinophilin, a new tumor inhibitory substance produced by Streptomyces. I. J. Antibiot. 7A, 107–112.
3. Yokoi, K., Nagaoka, K., and Nakashima, T. (1986). Azinomycins A and B, new antitumor antibiotics. II. Chemical structures. Chem. Pharm. Bull. (Tokyo) 34, 4554–4561.
4. Armstrong, R.W., Salvati, M.E., and Nguyen, M. (1992). Novel interstrand cross-links induced by the antitumor antibiotic carzinophillin/azinomycin B. J. Am. Chem. Soc. 114, 3144–3145.
5. Hartley, J.A., Hazrati, A., Kelland, L.R., Khanim, R., Shipman, M., Suzenet, F., and Walker, L.F. (2000). A synthetic azinomycin analogue with demonstrated DNA cross-linking activity: Insights into the mechanism of action of this class of antitumor agent. Angew. Chem. Int. Ed. Engl. 39, 3467–3470.
6. Coleman, R.S., Perez, R.J., Burk, C.H., and Navarro, A. (2002). Studies on the mechanism of action of azinomycin B: definition of regioselectivity and sequence selectivity of DNA cross-link formation and clarification of the role of the naphthoate. J. Am. Chem. Soc. 124, 13008–13017.
7. LePla, R.C., Landreau, C.A.S., Shipman, M., and Jones, G.D. (2005). On the origin of the DNA sequence selectivity of the azinomycins. Org. Biomol. Chem. 3, 1174–1175.
8. Kelly, G.T., Liu, C., Smith, R., III, Coleman, R.S., and Watanabe, C.M.H. (2006). Cellular effects induced by the antitumor agent azinomycin B. Chem. Biol. 13, 485–492.
9. Zhao, Qunfei, Qingli He, Wei Ding, Mancheng Tang, Qianjin Kang, Yi Yu, Wei Deng, Qi Zhang, Jie Fang, Gongli Tang, and Wen Liu. "Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis." Chemistry & Biology 15.7 (2008): 693-705. Web.