Format:
Online-Ressource
ISSN:
1521-3773
Content:
Abstract: Modular trans‐acyltransferase polyketide synthases (trans‐AT PKSs) are enzymatic assembly lines that biosynthesize complex polyketide natural products. Relative to their better studied cis‐AT counterparts, the trans‐AT PKSs introduce remarkable chemical diversity into their polyketide products. A notable example is the lobatamide A PKS, which incorporates a methylated oxime. Here we demonstrate biochemically that this functionality is installed on‐line by an unusual oxygenase‐containing bimodule. Furthermore, analysis of the oxygenase crystal structure coupled with site‐directed mutagenesis allows us to propose a model for catalysis, as well as identifying key protein‐protein interactions that support this chemistry. Overall, our work adds oxime‐forming machinery to the biomolecular toolbox available for trans‐AT PKS engineering, opening the way to introducing such masked aldehyde functionalities into diverse polyketides.
In:
day:11
In:
month:07
In:
year:2023
In:
extent:10
In:
Angewandte Chemie / International edition, Weinheim : Wiley-VCH, 1962-, (11.07.2023) (gesamt 10), 1521-3773
Language:
English
DOI:
10.1002/anie.202304481
URN:
urn:nbn:de:101:1-2023071215205176559896
URL:
https://doi.org/10.1002/anie.202304481
URL:
https://nbn-resolving.org/urn:nbn:de:101:1-2023071215205176559896
URL:
https://d-nb.info/1295816369/34
URL:
https://doi.org/10.1002/anie.202304481
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