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Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

Stephan Klopries, Uschi Sundermann and Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674. https://doi.org/10.3762/bjoc.9.75

Supporting Information

Supporting Information File 1: NMR spectra of synthesized compounds and ESI–MS spectra of D₃-propionate incorporation.
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Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

Stephan Klopries, Uschi Sundermann and Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674. https://doi.org/10.3762/bjoc.9.75

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Klopries, S.; Sundermann, U.; Schulz, F. Beilstein J. Org. Chem. 2013, 9, 664–674. doi:10.3762/bjoc.9.75

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TY  - JOUR
A1  - Klopries, Stephan
A1  - Sundermann, Uschi
A1  - Schulz, Frank
T1  - Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis
JF  - Beilstein Journal of Organic Chemistry
PY  - 2013///
VL  - 9
SP  - 664
EP  - 674
SN  - 1860-5397
DO  - 10.3762/bjoc.9.75
PB  - Beilstein-Institut
JA  - Beilstein J. Org. Chem.
UR  - https://doi.org/10.3762/bjoc.9.75
KW  - biosynthesis
KW  - coenzyme A
KW  - malonic acid
KW  - polyketide
KW  - polyketide synthase
N2  - Polyketides are biosynthesized through consecutive decarboxylative Claisen condensations between a carboxylic acid and differently substituted malonic acid thioesters, both tethered to the giant polyketide synthase enzymes. Individual malonic acid derivatives are typically required to be activated as coenzyme A-thioesters prior to their enzyme-catalyzed transfer onto the polyketide synthase. Control over the selection of malonic acid building blocks promises great potential for the experimental alteration of polyketide structure and bioactivity. One requirement for this endeavor is the supplementation of the bacterial polyketide fermentation system with tailored synthetic thioester-activated malonates. The membrane permeable N-acetylcysteamine has been proposed as a coenzyme A-mimic for this purpose. Here, the incorporation efficiency into different polyketides of N-acetylcysteamine activated methylmalonate is studied and quantified, showing a surprisingly high and transferable activity of these polyketide synthase substrate analogues in vivo.
ER  -

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