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Issue 6, 2008
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The unusual macrocycle forming thioesterase of mycolactone

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Abstract

Mycolactone is a polyketide natural product secreted by Mycobacterium ulcerans, the organism responsible for the tropical skin disease Buruli ulcer. The finding that this small molecule virulence factor is sufficient to reconstitute the necrotic pathology associated with Buruli ulcer suggests that a better understanding of mycolactone biosynthesis, particularly the processes which are distinct from those in human metabolism, may provide a unique avenue for the development of selective therapeutics. In the present study we have cloned, expressed, and biochemically characterized the putative macrocycle forming thioesterase for mycolactone, MLSA2 TE. We have evaluated the enzyme both as the truncated thioesterase domain and as a carrier protein-linked didomain construct. The results of these analyses distinguish MLSA2 TE from traditional fatty acid and polyketide synthase TE-domains in terms of its sequence, kinetic parameters, and susceptibility to traditional active-site directed inhibitors. These findings suggest that MLSA2 TE utilizes a unique biochemical mechanism for macrocycle formation.

Graphical abstract: The unusual macrocycle forming thioesterase of mycolactone

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Publication details

The article was received on 29 Jan 2008, accepted on 12 Mar 2008 and first published on 16 Apr 2008


Article type: Paper
DOI: 10.1039/B801397G
Citation: Mol. BioSyst., 2008,4, 663-671
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    The unusual macrocycle forming thioesterase of mycolactone

    J. L. Meier, T. Barrows-Yano, T. L. Foley, C. L. Wike and M. D. Burkart, Mol. BioSyst., 2008, 4, 663
    DOI: 10.1039/B801397G

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