Structural Basis for Intermodular Communication in Assembly-Line Polyketide Biosynthesis
bioRxiv, ISSN: 2692-8205
2024
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Structural Basis for Intermodular Communication in Assembly-Line Polyketide Biosynthesis
2024 MAY 16 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Life Science Daily -- According to news reporting based on a preprint
Article Description
Assembly-line polyketide synthases are large multienzyme systems with considerable potential for genetic reprogramming. To investigate the mechanisms by which reactive biosynthetic intermediates are directionally channeled across a defined sequence of active sites in a naturally occurring assembly line, we employed a bifunctional reagent to crosslink transient domain-domain interfaces of the 6-deoxyerythronolide B synthase. Structural resolution of these crosslinked states by single-particle cryogenic electron microscopy (cryo-EM) together with statistical per-particle image analysis of cryo-EM data revealed ketosynthase – acyl carrier protein (KS-ACP) interactions that discriminate between intra- and inter-modular communication, while reinforcing the relevance of asymmetric conformations during the catalytic cycle. Our findings provide a new foundation for the structure-based design of hybrid polyketide synthases comprised of biosynthetic modules from different assembly lines.
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