| Autor: |
Guifa Zhai, Yan Zhu, Guo Sun, Fan Zhou, Zhou Hong, Chuan Dong, Peter Leadlay, Kui Hong, Zixin Deng, Fuling Zhou, Yuhui Sun |
| Rok vydání: |
2022 |
| DOI: |
10.21203/rs.3.rs-1721330/v1 |
| Popis: |
Exploring interactions among modules in modular polyketide synthase (PKS) is very important for understanding the overall biosynthetic process and for engineering PKS assembly-lines. Herein, we show that intermodule recognition between the enoylreductase domain ER1/2 inside module 1/2 and the ketosynthase domain KS3 inside module 3 is required for the cross-module enoylreduction in azalomycin F (AZL) biosynthesis. We also show that KS4 of module 4 acts as a gatekeeper facilitating cross-module enoylreduction. Additionally, evidence is provided that module 3 and module 6 in the AZL PKS are evolutionarily homologous, which make evolution-oriented PKS engineering possible. These results reveal an unprecedented intermodule recognition furthering understanding of the mechanism of the PKS assembly-line, thus providing new insights into PKS engineering. It also reveals that gene duplication/conversion and subsequent combinations may be a neofunctionalization process in modular PKS assembly-lines, hence providing a new case for supporting investigation of modular PKS evolution. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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