Journal of the American Chemical Society
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(10) Knappe, T. A.; Manzenrieder, F.; Mas-Moruno, C.; Linne, U.;
Sasse, F.; Kessler, H.; Xie, X.; Marahiel, M. A. Angew. Chem. Int. Ed.
2011, 50, 8714.
1
2
3
4
5
6
7
8
(11) Tianero, M. D.; Donia, M. S.; Young, T. S.; Schultz, P. G.;
Schmidt, E. W. J. Am. Chem. Soc. 2012, 134, 418.
(12) Houssen, W. E.; Bent, A. F.; McEwan, A. R.; Pieiller, N.;
Tabudravu, J.; Koehnke, J.; Mann, G.; Adaba, R. I.; Thomas, L.;
Hawas, U. W.; Liu, H.; Schwarz-Linek, U.; Smith, M. C.; Naismith,
J. H.; Jaspars, M. Angew. Chem. Int. Ed. 2014, 53, 14171.
(13) van Heel, A. J.; Mu, D.; Montalban-Lopez, M.; Hendriks, D.;
Kuipers, O. P. ACS Synth. Biol. 2013, 2, 397.
9
(14) Deane, C. D.; Mitchell, D. A. J. Ind. Microbiol. Biotechnol. 2014,
41, 315.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 4. Zones of growth inhibition by nukacin ISK-1 and
analogues against L. lactis HP. A total of 10 μL of solution at
the concentrations listed was applied to each spot.
(15) Molloy, E. M.; Ross, R. P.; Hill, C. Biochem. Soc. Trans. 2012,
40, 1492.
(16) Bierbaum, G.; Sahl, H. G. Curr. Pharm. Biotechnol. 2009, 10, 2.
(17) Nagao, J.; Harada, Y.; Shioya, K.; Aso, Y.; Zendo, T.; Nakayama,
J.; Sonomoto, K. Biochem. Biophys. Res. Commun. 2005, 336, 507.
(18) Oman, T. J.; Knerr, P. J.; Bindman, N. A.; Vélasquez, J. E.; van
der Donk, W. A. J. Am. Chem. Soc. 2012, 134, 6952.
(19) Shi, Y.; Yang, X.; Garg, N.; van der Donk, W. A. J. Am. Chem.
Soc. 2011, 133, 2338.
(20) Caetano, T.; Krawczyk, J. M.; Mosker, E.; Süssmuth, R. D.;
Mendo, S. Chem. Biol. 2011, 18, 90.
(21) Lin, Y.; Teng, K.; Huan, L.; Zhong, J. Microbiol. Res. 2011, 166,
146.
(22) Furgerson Ihnken, L. A.; Chatterjee, C.; van der Donk, W. A.
Biochemistry 2008, 47, 7352.
(23) Goto, Y.; Li, B.; Claesen, J.; Shi, Y.; Bibb, M. J.; van der Donk,
W. A. PLoS Biol. 2010, 8, e1000339.
(24) Plat, A.; Kluskens, L. D.; Kuipers, A.; Rink, R.; Moll, G. N. Appl.
Environ. Microbiol. 2011, 77, 604.
(25) Li, B.; Sher, D.; Kelly, L.; Shi, Y.; Huang, K.; Knerr, P. J.;
Joewono, I.; Rusch, D.; Chisholm, S. W.; van der Donk, W. A. Proc.
Natl. Acad. Sci. U.S.A. 2010, 107, 10430.
(26) Lohans, C. T.; Li, J. L.; Vederas, J. C. J. Am. Chem. Soc. 2014,
136, 13150.
(27) Ökesli, A.; Cooper, L. E.; Fogle, E. J.; van der Donk, W. A. J.
Am. Chem. Soc. 2011, 133, 13753.
(28) Bindman, N. A.; van der Donk, W. A. J. Am. Chem. Soc. 2013,
135, 10362.
(29) Tang, W.; van der Donk, W. A. Biochemistry 2012, 51, 4271.
(30) Garg, N.; Tang, W.; Goto, Y.; van der Donk, W. A. Proc. Natl.
Acad. Sci. U. S. A. 2012, 109, 5241.
(31) Bindman, N.; Merkx, R.; Koehler, R.; Herrman, N.; van der
Donk, W. A. Chem. Commun. 2010, 46, 8935.
(32) Fahnestock, S.; Rich, A. Science 1971, 173, 340.
(33) Guo, J.; Wang, J.; Anderson, J. C.; Schultz, P. G. Angew. Chem.
Int. Ed. Engl. 2008, 47, 722.
(34) England, P. M.; Lester, H. A.; Dougherty, D. A. Biochemistry
1999, 38, 14409.
(35) Watanabe, T.; Miyata, Y.; Abe, R.; Muranaka, N.; Hohsaka, T.
Chembiochem 2008, 9, 1235.
(36) Srinivasan, G.; James, C. M.; Krzycki, J. A. Science 2002, 296,
1459.
(37) Kobayashi, T.; Yanagisawa, T.; Sakamoto, K.; Yokoyama, S. J.
Mol. Biol. 2009, 385, 1352.
(38) Wang, Y. S.; Fang, X.; Wallace, A. L.; Wu, B.; Liu, W. R. J. Am.
Chem. Soc. 2012, 134, 2950.
(39) Wang, Y. S.; Fang, X.; Chen, H. Y.; Wu, B.; Wang, Z. U.; Hilty,
C.; Liu, W. R. ACS Chem. Biol. 2013, 8, 405.
(40) Tharp, J. M.; Wang, Y. S.; Lee, Y. J.; Yang, Y.; Liu, W. R. ACS
Chem. Biol. 2014, 9, 884.
(41) Levengood, M. R.; Kerwood, C. C.; Chatterjee, C.; van der
Donk, W. A. ChemBioChem 2009, 10, 911.
(42) Asaduzzaman, S. M.; Nagao, J.; Aso, Y.; Nakayama, J.;
Sonomoto, K. Appl. Environ. Microbiol. 2006, 72, 6012.
In conclusion, we produced analogs of lacticin 481 and nu-
kacin ISK-1 by hydrolytic removal of the leader peptide.
Unlike methods using commercial proteases, the ester
bond hydrolysis reaction is not sequence dependent and is
completely site-selective. Furthermore, the method can be
readily multiplexed. This general methodology may there-
fore find use for lanthipeptides and other classes of RiPPs,
and many applications can be envisioned in synthetic biol-
ogy when an N-terminal amino group is not important.
Supporting Information
Experimental procedures, supporting figures, and full au-
thor list for reference 1. This material is available free of
AUTHOR INFORMATION
Corresponding Authors
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was supported by the National Institutes of
Health (GM58822 to W.A.V. and CA161158 to W.R.L.).
REFERENCES
(1) Arnison, P. G.; Bibb, M. J.; Bierbaum, G.; Bowers, A. A.; Bugni, T.
S.; Bulaj, G.; Camarero, J. A.; Campopiano, D. J.; Challis, G. L.;
Clardy, J. et al. Nat. Prod. Rep. 2013, 30, 108.
(2) Velásquez, J. E.; van der Donk, W. A. Curr. Opin. Chem. Biol.
2011, 15, 11.
(3) Mohimani, H.; Kersten, R. D.; Liu, W. T.; Wang, M.; Purvine, S.
O.; Wu, S.; Brewer, H. M.; Pasa-Tolic, L.; Bandeira, N.; Moore, B. S.;
Pevzner, P. A.; Dorrestein, P. C. ACS Chem. Biol. 2014, 9, 1545.
(4) Maksimov, M. O.; Link, A. J. J. Ind. Microbiol. Biotechnol. 2014,
41, 333.
(5) Letzel, A. C.; Pidot, S. J.; Hertweck, C. BMC Genomics 2014, 15,
983.
(6) Zhang, Q.; Doroghazi, J. R.; Zhao, X.; Walker, M. C.; van der
Donk, W. A. Appl. Environ. Microb. 2015, doi:10.1128/AEM.00635.
(7) Levengood, M. R.; van der Donk, W. A. Bioorg. Med. Chem.
Lett. 2008, 18, 3025.
(8) Cortés, J.; Appleyard, A. N.; Dawson, M. J. Methods Enzymol.
2009, 458, 559.
(9) Rink, R.; Arkema-Meter, A.; Baudoin, I.; Post, E.; Kuipers, A.;
Nelemans, S. A.; Akanbi, M. H.; Moll, G. N. J. Pharmacol. Toxicol.
Methods 2010, 61, 210.
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