Circular logic: nonribosomal peptide-like macrocyclization with a ribosomal peptide catalyst - PubMed (original) (raw)

Circular logic: nonribosomal peptide-like macrocyclization with a ribosomal peptide catalyst

John A McIntosh et al. J Am Chem Soc. 2010.

Abstract

A protease from ribosomal peptide biosynthesis macrocyclizes diverse substrates, including those resembling nonribosomal peptide and hybrid polyketide-peptide products. The proposed mechanism is analogous to thioesterase-catalyzed chemistry, but the substrates are amide bonds rather than thioesters.

PubMed Disclaimer

Figures

Figure 1

Figure 1. Macrocyclization in ribosomal and nonribosomal synthesis

A) The nonribosomal TycC TE domain circularizes tyrocidines. PCP = peptidyl carrier protein. B) The ribosomally acting PatG protease circularizes patellamides and many other compounds. The proposed catalytic mechanism is indicated here. Tzl = thiazol(ine); MOzl = methyloxazoline.

Figure 2

Figure 2. Products of PatG macrocyclization

A) Representative known natural products cyclized by PatG, out of a total of 39 known natural products in this series. B) Macrocyclization products from this study, showing side-chain circularization (28, 43) and polyketide-like cyclization (41, 42).

Similar articles

Cited by

References

    1. Kopp F, Marahiel MA. Nat Prod Rep. 2007;24:735–49. - PubMed
    1. Burton PS, Conradi RA, Ho NF, Hilgers AR, Borchardt RT. J Pharm Sci. 1996;85:1336–40. - PubMed
    1. Donia MS, Schmidt EW, Lew M, Hung-Wen L. Comprehensive Natural Products II. Elsevier; Oxford: 2010. pp. 539–558.
    1. Donia MS, Ravel J, Schmidt EW. Nat Chem Biol. 2008;4:341–3. - PMC - PubMed
    1. Donia MS, Hathaway BJ, Sudek S, Haygood MG, Rosovitz MJ, Ravel J, Schmidt EW. Nat Chem Biol. 2006;2:729–35. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources