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. 2007 Feb 28;129(8):2212-3.
doi: 10.1021/ja067672v. Epub 2007 Feb 1.

On the substrate specificity of dehydration by lacticin 481 synthetase

Xingang Zhang  1 , Wilfred A van der Donk
Affiliations

On the substrate specificity of dehydration by lacticin 481 synthetase

Xingang Zhang et al. J Am Chem Soc. .

Abstract

Dehydroamino acids are valuable building blocks that are a challenge to incorporate synthetically into unprotected peptides. Lantibiotic synthetases possess dehydration activity that converts Ser and Thr residues in their peptide substrates into dehydroalanine and dehydrobutyrine residues, respectively. We show here that lacticin 481 synthetase can convert the Thr analogs (R)-3-EtSer, (R)-3-vinylSer, (R)-3-ethynylSer, and (R)-3-[(E)-propenyl]Ser into the corresponding dehydro amino acids when incorporated into its peptide substrate. This relaxed substrate specificity holds promise for using the enzyme for synthetic purposes and for lantibiotic engineering. On the other hand, (R)-3-PrSer, (R)-3-iPrSer, and allo-Thr are not substrates for the enzyme.

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Figures

Figure 1
Figure 1
Dehydration of LctA catalyzed by lacticin 481 synthetase (LctM). The truncated substrate used in this work is boxed.
Figure 2
Figure 2
MALDI-MS spectra of assays in which analogs of a truncated LctA peptide (LctA1-43) were incubated with LctM. Substrates are shown in red and assay products in blue. Substrates contained the following Ser/Thr analogs at position 42: (A) 1, (B) 6, (C) 5, and (D) 9. The asterisks denote oxidation products (+16) involving Met.
Scheme 1
Scheme 1
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References

    1. For selected examples, seeBodanszky M, Scozzie JA, Muramatsu I. J. Antibiot. 1970;23:9–12.Berdy J. Adv. Appl. Microbiol. 1974;18:309–406.Tori K, Tokura K, Okabe K, Ebata M, Otsuka H, Lukacs G. Tetrahedron Lett. 1976;3:185–188.Pascard C, Ducruix A, Lunel J, Prangé T. J. Am. Chem. Soc. 1977;99:6418–6423.Pearce CJ, Rinehart KL., Jr. J. Am. Chem. Soc. 1979;101:5069–5070.Pedras MSC, Taylor JT, Nakashima TT. J. Org. Chem. 1993;58:4778–4780.Hamann MT, Scheuer PJ. J. Am. Chem. Soc. 1993;115:5825–5826.Lau RC, Rinehart KL., Jr. J. Antibiot. 1994;47:1466–1472.For selected synthetic studies, seeSnider BB, Zeng H. J. Org. Chem. 2003;68:545–563.Nicolaou KC, Zak M, Safina BS, Lee SH, Estrada AA. Angew Chem Int Ed Engl. 2004;43:5092–5097.Ley SV, Priour A, Heusser C. Org. Lett. 2002;4:711–714.

    1. Palmer DE, Pattaroni C, Nunami K, Chadha RK, Goodman M, Wakamiya T, Fukase K, Horimoto S, Kitazawa M, Fujita H, Kubo A, Shiba T. J. Am. Chem. Soc. 1992;114:5634–5642.
    2. Lombardi A, D'Agostino B, Nastri F, D'Andrea LD, Filippelli A, Falciani M, Rossi F, Pavone V. Bioorg. Med. Chem. Lett. 1998;8:1153–1156. - PubMed
    3. Murkin AS, Tanner ME. J. Org. Chem. 2002;67:8389–8394. - PubMed
    4. Li B, Yu J-PJ, Brunzelle JS, Moll GN, van der Donk WA, Nair SK. Science. 2006;311:1464–1467. - PubMed
    1. Zhu Y, van der Donk WA. Org. Lett. 2001;3:1189–1192. - PubMed
    2. Galonic D, van der Donk WA, Gin DY. Chem.- Eur. J. 2003;24:5997–6006. - PubMed
    1. Schmidt U, Lieberknecht A, Wild J. Synthesis. 1988:159–172.
    2. Bonauer C, Walenczyk T, König B. Synthesis. 2006:1–20.
    1. Chatterjee C, Paul M, Xie L, van der Donk WA. Chem. Rev. 2005;105:633–684. - PubMed

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