Tailoring the Tag/Catcher System by Integrating Covalent Bonds and Noncovalent Interactions for Highly Efficient Protein Self-Assembly

Biomacromolecules. 2022 Sep 12;23(9):3936-3947. doi: 10.1021/acs.biomac.2c00765. Epub 2022 Aug 23.

Abstract

Covalent bonds and noncovalent interactions play crucial roles in enzyme self-assembly. Here, we designed a Tag/Catcher system named NGTag/NGCatcher in which the Catcher is a highly charged protein that can bind proteins with positively charged tails and rapidly form a stable isopeptide bond with NGTag. In this study, we present a multienzyme strategy based on covalent bonds and noncovalent interactions. In vitro, mCherry, YFP, and GFP can form protein-rich three-dimensional networks based on NGCatcher, NGTag, and RK (Arginine/Lysine) tails, respectively. Furthermore, this technology was applied to improve lycopene production in Escherichia coli. Three key enzymes were involved in lycopene production variants from Deinococcus wulumuqiensis R12 of NGCatcher_CrtE, NGTag_Idi, and RKIspARK, where the multienzyme complexes were clearly observed in vivo and in vitro, and the lycopene production in vivo was 17.8-fold higher than that in the control group. The NGTag/NGCatcher system will provide new opportunities for in vivo and in vitro multienzyme catalysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Escherichia coli* / genetics
  • Escherichia coli* / metabolism
  • Lycopene / metabolism
  • Multienzyme Complexes / metabolism
  • Proteins* / metabolism

Substances

  • Multienzyme Complexes
  • Proteins
  • Lycopene