Programmable biomolecular switches for rewiring flux in Escherichia coli

Synthetic biology aims to develop programmable tools to perform complex functions such as redistributing metabolic flux in industrial microorganisms. However, development of protein-level circuits is limited by availability of designable, orthogonal, and composable tools. Here, with the aid of engineered viral proteases and proteolytic signals, we build two sets of controllable protein units, which can be rationally configured to three tools. Using a protease-based dynamic regulation circuit to fine-tune metabolic flow, we achieve 12.63 g L-1 shikimate titer in minimal medium without inducer. In addition, the carbon catabolite repression is alleviated by protease-based inverter-mediated flux redistribution under multiple carbon sources. By coordinating reaction rate using a protease-based oscillator in E. coli, we achieve D-xylonate productivity of 7.12 g L-1 h-1 with a titer of 199.44 g L-1. These results highlight the applicability of programmable protein switches to metabolic engineering for valuable chemicals production.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:10

Enthalten in:

Nature communications - 10(2019), 1 vom: 21. Aug., Seite 3751

Sprache:

Englisch

Beteiligte Personen:

Gao, Cong [VerfasserIn]
Hou, Jianshen [VerfasserIn]
Xu, Peng [VerfasserIn]
Guo, Liang [VerfasserIn]
Chen, Xiulai [VerfasserIn]
Hu, Guipeng [VerfasserIn]
Ye, Chao [VerfasserIn]
Edwards, Harley [VerfasserIn]
Chen, Jian [VerfasserIn]
Chen, Wei [VerfasserIn]
Liu, Liming [VerfasserIn]

Links:

Volltext

Themen:

29MS2WI2NU
A1TA934AKO
EC 3.4.-
Endopeptidases
Escherichia coli Proteins
Glucose
IY9XDZ35W2
Journal Article
Research Support, Non-U.S. Gov't
Shikimic Acid
Viral Proteins
Xylonic acid
Xylose

Anmerkungen:

Date Completed 09.12.2019

Date Revised 10.01.2021

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-019-11793-7

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM300447345