Cyanobactins are a rapidly growing family of linear and cyclic peptides produced by cyanobacteria. Kawaguchipeptins A and B, two macrocyclic undecapeptides reported earlier from Microcystis aeruginosa NIES-88, are shown to be products of the cyanobactin biosynthetic pathway. The 9 kb kawaguchipeptin (kgp) gene cluster was identified in a 5.26 Mb draft genome of Microcystis aeruginosa NIES-88. We verified that this gene cluster is responsible for the production of the kawaguchipeptins through heterologous expression of the kgp gene cluster in Escherichia coli. The KgpF prenyltransferase was overexpressed and was shown to prenylate C-3 of Trp residues in both linear and cyclic peptides in vitro. Our findings serve to further enhance the structural diversity of cyanobactins to include tryptophan-prenylated cyclic peptides.

Biomedical Sciences Research Complex University of St Andrews North Haugh St Andrews Fife KY16 9ST UK

Department of Chemistry University of Pittsburgh 219 Parkman Avenue Pittsburgh PA 15260 USA

Institute for Biomedical Technologies Italy

Institute of Medical Sciences University of Aberdeen Aberdeen AB25 2ZD UK

Institute of Microbiology AS CR v v i Center ALGATECH Třeboň Czech Republic

Marine Biodiscovery Centre Department of Chemistry University of Aberdeen Meston Walk Aberdeen AB24 3UE UK

Microbiology and Biotechnology Division Department of Food and Environmental Sciences P O Box 56 Viikki Biocenter Viikinkaari 9 00014 University of Helsinki Finland

Pharmacognosy Department Faculty of Pharmacy Mansoura University Mansoura 35516 Egypt

University of South Bohemia Faculty of Science Department of Ecosystem Biology České Budějovice Czech Republic

Angew Chem Int Ed Engl. 2017 Jan 9;56(2):433. doi: 10.1002/anie.201609949. PubMed

See more in PubMed

Arnison PG, Bibb MJ, Bierbaum G, Bowers AA, Bugni TS, Bulaj G, Camarero JA, Campopiano DJ, Challis GL, Clardy J. Nat Prod Rep. 2013;30:108–160. PubMed PMC

Sivonen K, Leikoski N, Fewer DP, Jokela J. Appl Microbiol Biotechnol. 2010;86:1213–1225. PubMed PMC

Leikoski N, Fewer DP, Sivonen K. Appl Environ Microbiol. 2009;75:853–857. PubMed PMC

Leikoski N, Fewer DP, Jokela J, Wahlsten M, Rouhiainen L, Sivonen K. Appl Environ Microbiol. 2010;76:701–709. PubMed PMC

Leikoski N, Liu L, Jokela J, Wahlsten M, Gugger M, Calteau A, Permi P, Kerfeld CA, Sivonen K, Fewer DP. Chem Biol. 2013;20:1033–1043. PubMed

Donia MS, Schmidt EW. Chem Biol. 2011;18:508–519. PubMed PMC

Lee J, McIntosh J, Hathaway BJ, Schmidt EW. J Am Chem Soc. 2009;131:2122–2124. PubMed PMC

McIntosh JA, Donia MS, Schmidt EW. J Am Chem Soc. 2010;132:4089–4091. PubMed PMC

Schmidt EW, Nelson JT, Rasko DA, Sudek S, Eisen JA, Haygood MG, Ravel J. Proc Natl Acad Sci U S A. 2005;102:7315–7320. PubMed PMC

Donia MS, Hathaway BJ, Sudek S, Haygood MG, Rosovitz M, Ravel J, Schmidt EW. Nature chemical biology. 2006;2:729–735. PubMed

Donia MS, Ravel J, Schmidt EW. Nature chemical biology. 2008;4:341–343. PubMed PMC

McIntosh JA, Donia MS, Nair SK, Schmidt EW. J Am Chem Soc. 2011;133:13698–13705. PubMed PMC

Ishida K, Matsuda H, Murakami M, Yamaguchi K. Tetrahedron. 1996;52:9025–9030.

Ishida K, Matsuda H, Murakami M, Yamaguchi K. J Nat Prod. 1997;60:724–726. PubMed

Delcher AL, Bratke KA, Powers EC, Salzberg SL. Bioinformatics. 2007;23:673–679. PubMed PMC

Lowe TM, Eddy SR. Nucleic Acids Res. 1997;25:0955–964. PubMed PMC

Casey PJ, Seabra MC. J Biol Chem. 1996;271:5289–5292. PubMed

Gibbs JB, Oliff A. Annu Rev Pharmacol Toxicol. 1997;37:143–166. PubMed

McIntosh JA, Donia MS, Schmidt EW. Nat Prod Rep. 2009;26:537–559. PubMed PMC

McIntosh JA, Lin Z, Tianero MDB, Schmidt EW. ACS chemical biology. 2013;8:877–883. PubMed PMC

Schmidt EW, Donia MS. Meth Enzymol. 2009;458:575–596. PubMed PMC

Magnuson R, Solomon J, Grossman AD. Cell. 1994;77:207–216. PubMed

Tsuji F, Kobayashi K, Okada M, Yamaguchi H, Ojika M, Sakagami Y. Bioorg Med Chem Lett. 2011;21:4041–4044. PubMed

Li S. Nat Prod Rep. 2010;27:57–78. PubMed

Wallwey C, Li S. Nat Prod Rep. 2011;28:496–510. PubMed

Hulvová H, Galuszka P, Frébortová J, Frébort I. Biotechnol Adv. 2013;31:79–89. PubMed

Williams RM, Stocking EM, Sanz-Cervera JF. Top Curr Chem. 2000;209:97–173.

Kotai J. Norwegian Institute for Water Research. Oslo. 1972;11:5.

Fewer DP, Osterholm J, Rouhiainen L, Jokela J, Wahlsten M, Sivonen K. Appl Environ Microbiol. 2011;77:8034–8040. PubMed PMC

Rutherford K, Parkhill J, Crook J, Horsnell T, Rice P, Rajandream MA, Barrell B. Bioinformatics. 2000;16:944–945. PubMed

Zdobnov, Apweile 2001

Tatusov RL, Fedorova ND, Jackson JD, Jacobs AR, Kiryutin B, Koonin EV, Krylov DM, Mazumder R, Mekhedov SL, Nikolskaya AN, Rao BS, et al. BMC Bioinformatics. 2003;4:41. PubMed PMC

Ziemert N, Ishida K, Quillardet P, Bouchier C, Hertweck C, de Marsac NT, Dittmann E. Appl Environ Microbiol. 2008;74:1791–1797. PubMed PMC

Shanks RM, Kadouri DE, MacEachran DP, O’Toole GA. Plasmid. 2009;62:88–97. PubMed PMC