Tuning architectural organization of eukaryotic P450 system to boost bioproduction in Escherichia coli

Yikui Li, Jie Li, Wei-Kang Chen, Yang Li, Sheng Xu, Linwei Li, Bing Xia and Ren Wang ()
Additional contact information
Yikui Li: Jiangsu Province and Chinese Academy of Sciences
Jie Li: Jiangsu Province and Chinese Academy of Sciences
Wei-Kang Chen: Jiangsu Province and Chinese Academy of Sciences
Yang Li: Jiangsu Province and Chinese Academy of Sciences
Sheng Xu: Jiangsu Province and Chinese Academy of Sciences
Linwei Li: Jiangsu Province and Chinese Academy of Sciences
Bing Xia: Jiangsu Province and Chinese Academy of Sciences
Ren Wang: Jiangsu Province and Chinese Academy of Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract Eukaryotic cytochrome P450 enzymes, generally colocalizing with their redox partner cytochrome P450 reductase (CPR) on the cytoplasmic surface of organelle membranes, often perform poorly in prokaryotic cells, whether expressed with CPR as a tandem chimera or free-floating individuals, causing a low titer of heterologous chemicals. To improve their biosynthetic performance in Escherichia coli, here, we architecturally design self-assembled alternatives of eukaryotic P450 system using reconstructed P450 and CPR, and create a set of N-termini-bridged P450-CPR heterodimers as the counterparts of eukaryotic P450 system with N-terminus-guided colocalization. The covalent counterparts show superior and robust biosynthetic performance, and the N-termini-bridged architecture is validated to improve the biosynthetic performance of both plant and human P450 systems. Furthermore, the architectural configuration of protein assemblies has an inherent effect on the biosynthetic performance of N-termini-bridged P450-CPR heterodimers. The results suggest that spatial architecture-guided protein assembly could serve as an efficient strategy for improving the biosynthetic performance of protein complexes, particularly those related to eukaryotic membranes, in prokaryotic and even eukaryotic hosts.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54259-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54259-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54259-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().