Organic Letters
Letter
The structures of azoxymycins A and C indicate that they
contain two sets of identical subunits which are linked by an
azoxy bond. Moreover, the structure of azoxymycin B implies
that it contains two azoxy bond-linked different subunits. Their
biosynthetic pathway suggests that azoxymycins A and C are
synthesized from two identical precursors, and azoxymycin B is
synthesized from two different precursors. While the structure
of azoxymycin C is deduced without NMR spectra, the perfect
match for the azoxymycins’ biosynthetic pathway and structures
suggests that the deduced structure of azoxymycin C is correct.
Furthermore, the National Center for Biotechnology
Information (NCBI) genome database search revealed that
azoxymycin biosynthesis gene clusters are spread among several
other Streptomyces species, such as Streptomyces lydicus (99%
(2) Zhang, J.; Shreeve, J. n. M. J. Am. Chem. Soc. 2014, 136, 4437.
(
3) Wang, Y.; Li, S.; Li, Y.; Zhang, R.; Wang, D.; Pang, S. J. Mater.
Chem. A 2014, 2, 20806.
4) Folcia, C. L.; Alonso, I.; Ortega, J.; Etxebarria, J.; Pintre, I.; Ros,
M. B. Chem. Mater. 2006, 18, 4617.
5) Chilaya, G.; Chanishvili, A.; Petriashvili, G.; Barberi, R.;
(
(
Bartolino, R.; Cipparrone, G.; Mazzulla, A.; Shibaev, P. V. Adv.
Mater. 2007, 19, 565.
(6) Mykytiuk, T.; Ilchishin, I.; Yaroshchuk, O.; Kravchuk, R.; Li, Y.;
Li, Q. Opt. Lett. 2014, 39, 6490.
(7) Iamsaard, S.; Aßhoff, S. J.; Matt, B.; Kudernac, T.; Cornelissen, J.
J.; Fletcher, S. P.; Katsonis, N. Nat. Chem. 2014, 6, 229.
(
8) Yamada, M.; Kondo, M.; Mamiya, J. I.; Yu, Y. L.; Kinoshita, M.;
Barrett, C. J.; Ikeda, T. Angew. Chem., Int. Ed. 2008, 47, 4986.
9) Khoo, I.-C. Liquid crystals: physical properties and nonlinear optical
phenomena; John Wiley & Sons: 2007; Vol. 64.
10) Ye, Y.; Aulinger, K.; Arnold, N.; Spahl, W.; Steglich, W.
Tetrahedron Lett. 1997, 38, 8013.
11) Garg, R. P.; Ma, Y.; Hoyt, J. C.; Parry, R. J. Mol. Microbiol. 2002,
(
24
identity) and Streptomyces aureus (88% identity). Their gene
cluster arrangement was almost the same as that of the
azoxymycin biosynthesis cluster in S. chattanoogensis L10
(
(
(
Figure 4D and Table S2). Interestingly, S. lydicus and S.
4
6, 505.
25,26
aureus both show yellow color,
which might be caused by
(12) Omura, S.; Otoguro, K.; Imamura, N.; Kuga, H.; Takahashi, Y.;
the azoxymycin-like compounds synthesized by these clusters.
The existence of the azoxymycin biosynthesis gene cluster in
other Streptomyces species implies that these aromatic azoxy
natural products might have some kind of bioactivity similar to
that of these Streptomyces.
To summarize, three novel aromatic azoxy natural products,
azoxymycins A, B, and C, were isolated and identified from S.
chattanoogensis L10. All three azoxymycins showed light
inducible properties. Their biosynthetic pathway was charac-
terized and strongly supported by gene deletion experiments.
The discovery and biosynthesis of azoxymycins suggest that
these promising azoxy liquid crystalline compounds could be
biologically synthesized in replacement of traditional chemical
methods.
Masuma, R.; Tanaka, Y.; Tanaka, H.; Su, X.; You, E. J. Antibiot. 1987,
40, 623.
(
13) Ding, L.; Ndejouong, B. L. T.; Maier, A.; Fiebig, H. H.;
Hertweck, C. J. Nat. Prod. 2012, 75, 1729.
14) Takahashi, Y.; Nakayama, M.; Watanabe, I.; Deushi, T.;
Ishiwata, H.; Shiratsuchi, M.; Otani, G. J. Antibiot. 1989, 42, 1541.
15) Nakayama, M.; Takahashi, Y.; Itoh, H.; Kamiya, K.; Shiratsuchi,
M.; Otani, G. J. Antibiot. 1989, 42, 1535.
16) Kunitake, H.; Hiramatsu, T.; Kinashi, H.; Arakawa, K.
(
(
(
ChemBioChem 2015, 16, 2237.
(17) Garg, R. P.; Qian, X. L.; Alemany, L. B.; Moran, S.; Parry, R. J.
Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 6543.
(18) Basch, H.; Hoz, T. Mol. Phys. 1997, 91, 789.
(
19) Badovinac, I. J.; Orlic, N.; Gellini, C.; Moroni, L.; Salvi, P. R. J.
Mol. Struct. 2009, 924−926, 62.
20) Aronzon, D.; Levy, E. P.; Collings, P. J.; Chanishvili, A.; Chilaya,
G.; Petriashvili, G. Liq. Cryst. 2007, 34, 707.
21) Rui, Z.; Petrickova, K.; Skanta, F.; Pospisil, S.; Yang, Y.; Chen,
C. Y.; Tsai, S. F.; Floss, H. G.; Petricek, M.; Yu, T. W. J. Biol. Chem.
010, 285, 24915.
22) Gust, B.; Challis, G. L.; Fowler, K.; Kieser, T.; Chater, K. F. Proc.
Natl. Acad. Sci. U. S. A. 2003, 100, 1541.
23) Potterat, O.; Zahner, H.; Metzger, J. W.; Freund, S. Helv. Chim.
(
ASSOCIATED CONTENT
Supporting Information
■
(
*
S
2
(
(
Experiment details, biological assays, NMR, MS, HPLC,
UV/vis spectra of compounds described in the text
Acta 1994, 77, 569.
(24) Han, X.; Li, M.; Ding, Z.; Zhao, J.; Ji, K.; Wen, M.; Lu. J.
Bacteriol. 2012, 194, 5472.
(
(
25) Takeuchi, M.; Inukai, M.; Enokita, R.; Iwado, S.; Takahashi, S.;
Arai, M. J. Antibiot. 1980, 33, 1213.
26) Ando, K.; Oishi, H.; Hirano, S.; Okutomi, T.; Suzuki, K.;
Okazaki, H.; Sawada, M.; Sagawa, T. J. Antibiot. 1971, 24, 347.
AUTHOR INFORMATION
■
(
*
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by Zhejiang Provincial Natural
Science Foundation of China (No. LZ12C01001), the National
Natural Science Foundation of China (Nos. 31520103901 and
3
(
1200600), the National Basic Research Program of China
No. 2012CB721005), and National High Technology
Research & Development Program of China (No.
2012AA02A706).
REFERENCES
1) Jagtap, N.; Ramaswamy, V. Appl. Clay Sci. 2006, 33, 89.
■
(
D
Org. Lett. XXXX, XXX, XXX−XXX