Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Feb 16;133(6):1971-7.
doi: 10.1021/ja109226s. Epub 2011 Jan 19.

Structure and biosynthesis of the marine streptomycete ansamycin ansalactam A and its distinctive branched chain polyketide extender unit

Micheal C Wilson  1 , Sang-Jip Nam, Tobias A M Gulder, Christopher A Kauffman, Paul R Jensen, William Fenical, Bradley S Moore
Affiliations

Structure and biosynthesis of the marine streptomycete ansamycin ansalactam A and its distinctive branched chain polyketide extender unit

Micheal C Wilson et al. J Am Chem Soc. .

Abstract

Reported is the structure and biosynthesis of ansalactam A, an ansamycin class polyketide produced by an unusual modification of the polyketide pathway. This new metabolite, produced by a marine sediment-derived bacterium of the genus Streptomyces , possesses a novel spiro γ-lactam moiety and a distinctive isobutyryl polyketide fragment observed for the first time in this class of natural products. The structure of ansalactam A was defined by spectroscopic methods including X-ray crystallographic analysis. Biosynthetic studies with stable isotopes further led to the discovery of a new, branched chain polyketide synthase extender unit derived from (E)-4-methyl-2-pentenoic acid for polyketide assembly observed for the first time in this class of natural products.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Structure determination of ansalactam A (4). (A) COSY and key HMBC correlations for structure elucidation of ansalactam A (4). (B) Selected key ROESY correlations for determination of geometries and the relative configurations for ansalactam A (4).
Figure 2
Figure 2
Mosher's ester analysis of the polyol 5. (A) ΔδS-R of 1H for S- and R-bis-MTPA esters of 5, and (B) rotation model for determination of relative configurations for C-19 and C-20
Figure 3
Figure 3
Mosher's ester analysis of the diol 7. (A) ΔδS-R of 1H for S- and R-bis-MTPA esters of 7, and (B-E) rotation models for determination of relative configuration for C-16.
Figure 4
Figure 4
ORTEP plot of the final X-ray structure of 5 depicting the absolute configuration.
Figure 5
Figure 5
Biosynthetic origin of the carbons of the linearized PKS precursors of 4 compared to well characterized ansamycins and proposed biosynthesis of the C-22-C-27 branched extender unit.
Scheme 1
Scheme 1
Preparation of polyol 5 from ansalactam A (4).
Scheme 2
Scheme 2
Preparation of diol 7 from ansalactam A (5)
See this image and copyright information in PMC

References

    1. Floss HG. J. Nat. Prod. 2006;69:158. - PubMed
    1. August PR, Tang L, Yoon YJ, Ning S, Muller R, Yu TW, Taylor M, Hoffmann D, Kim CG, Zhang X, Hutchinson CR, Floss HG. Chem. Biol. 1998;5:69. - PubMed
    1. Floss HG, Yu TW. Chem. Rev. 2005;105:621. - PubMed
    1. Gulder TAM, Moore BS. Curr. Opin. Microbiol. 2009;12:252. - PMC - PubMed
    1. Fenical W, Jensen PR. Nat Chem Biol. 2006;2:666. - PubMed

Publication types

MeSH terms