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Evolving biosynthetic tangos negotiate mechanistic landscapes

Abstract

The dependence of polyketide synthase and terpene cyclase mechanistic adaptation on the chemistry of their oligomeric substrates illuminates a convergent evolutionary strategy for shaping cyclization in these otherwise disparate reactions. Evolution of these enzyme families relies on rhythmic tangos, in which the enzymes and substrates together determine product outcome by negotiating decision networks governing intrinsic and induced chemical reactivities.

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Figure 1: Metabolic diversity via divergent intramolecular cyclization.
Figure 2: Convergent features of 'uber-adaptable' cyclases and their oligomeric substrates.
Figure 3: Biosynthetic tangos in the shade of a branching metabolic diversification tree.

Rebecca Henretta

Figure 4: Comparison of postcyclization reactions in the SC (left) and PKS III (right) 'reaction chambers'.

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Acknowledgements

The authors acknowledge support from the Howard Hughes Medical Institute, the US National Institutes of Health and the US National Science Foundation.

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Austin, M., O'Maille, P. & Noel, J. Evolving biosynthetic tangos negotiate mechanistic landscapes. Nat Chem Biol 4, 217–222 (2008). https://doi.org/10.1038/nchembio0408-217

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