Clicking into Place: Interfacing Terminal Alkyne Biosynthesis with Polyketide Synthases

Passmore, Munro; Jenner, Matthew

doi:10.1016/j.tibtech.2020.04.001

Cited by 1 publication

(1 citation statement)

References 8 publications

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“…Harnessing the terminal alkyne biosynthetic machinery from the jamaicamide B type I PKS pathway enabled access to in trans loading of alkyne polyketides onto noncognate type I PKS enzymes. This process was optimized through the strategic modification of the jamaicamide B ACP via docking domain installation and site-directed mutagenesis (107,108). The selective, copper-catalyzed reaction of the terminal alkyne with an azide-containing fluorophore or mass tag can potentially enable subsequent visualization via fluorescence or mass spectrometry.…”

Section: Connections To Other Biosynthetic Pathways That Use Assembly Line Enzymologymentioning

confidence: 99%

Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways

Sulpizio¹,

Crawford²,

Koweek³

et al. 2021

Journal of Biological Chemistry

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Type II polyketide synthases (PKSs) are protein assemblies, encoded by biosynthetic gene clusters in microorganisms, that manufacture structurally complex and pharmacologically relevant molecules. Acyl carrier proteins (ACPs) play a central role in biosynthesis by shuttling malonyl-based building blocks and polyketide intermediates to catalytic partners for chemical transformations. Because ACPs serve as central hubs in type II PKSs, they can also represent roadblocks to successfully engineering synthases capable of manufacturing ‘unnatural natural products.’ Therefore, understanding ACP conformational dynamics and protein interactions is essential to enable the strategic redesign of type II PKSs. However, the inherent flexibility and transience of ACP interactions pose challenges to gaining insight into ACP structure and function. In this review, we summarize how the application of chemical probes and molecular dynamic simulations has increased our understanding of the structure and function of type II PKS ACPs. We also share how integrating these advances in type II PKS ACP research with newfound access to key enzyme partners, such as the ketosynthase-chain length factor, sets the stage to unlock new biosynthetic potential.

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Section: Connections To Other Biosynthetic Pathways That Use Assembly Line Enzymologymentioning

confidence: 99%

Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways

Sulpizio¹,

Crawford²,

Koweek³

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

Clicking into Place: Interfacing Terminal Alkyne Biosynthesis with Polyketide Synthases

Cited by 1 publication

References 8 publications

Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways

Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways

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