Gene editing enables rapid engineering of complex antibiotic assembly lines

  26 November 2021

Re-engineering biosynthetic assembly lines, including nonribosomal peptide synthetases (NRPS) and related megasynthase enzymes, is a powerful route to new antibiotics and other bioactive natural products that are too complex for chemical synthesis. However, engineering megasynthases is very challenging using current methods. Here, we describe how CRISPR-Cas9 gene editing can be exploited to rapidly engineer one of the most complex megasynthase assembly lines in nature, the 2.0 MDa NRPS enzymes that deliver the lipopeptide antibiotic enduracidin. Gene editing was used to exchange subdomains within the NRPS, altering substrate selectivity, leading to ten new lipopeptide variants in good yields. 

Further reading: Nature Communications
Author(s): Wei Li Thong, Yingxin Zhang, Ying Zhuo, Katherine J. Robins, Joanna K. Fyans, Abigail J. Herbert, Brian J. C. Law & Jason Micklefield
Smart Innovations  
Back

OUR UNDERWRITERS

Unrestricted financial support by:

Antimicrobial Resistance Fighter Coalition

Evotec

JSS University





Technology Database

Display your AMR Technology, Product and Service

Suppliers and Users of Technologies, Products and Services benefit from CAPI.
CAPI (Continuous AMR Partnering Initiative) unites Suppliers and Users worldwide with the aim to add to the curbing of AMR.

Read more and make your own Technology Page >>
What is going on with AMR?
Stay tuned with remarkable global AMR news and developments!