Engineering yeast metabolism for the discovery and production of polyamines and polyamine analogues
Journal article, 2021
Structurally complex and diverse polyamines and polyamine analogues are potential therapeutics and agrochemicals that can address grand societal challenges, for example, healthy ageing and sustainable food production. However, their structural complexity and low abundance in nature hampers either bulk chemical synthesis or extraction from natural resources. Here we reprogrammed the metabolism of baker’s yeast Saccharomyces cerevisiae and recruited nature’s diverse reservoir of biochemical tools to enable a complete biosynthesis of multiple polyamines and polyamine analogues. Specifically, we adopted a systematic engineering strategy to enable gram-per-litre-scale titres of spermidine, a central metabolite in polyamine metabolism. To demonstrate the potential of our polyamine platform, various polyamine synthases and ATP-dependent amide-bond-forming systems were introduced for the biosynthesis of natural and unnatural polyamine analogues. The yeast platform serves as a resource to accelerate the discovery and production of polyamines and polyamine analogues, and thereby unlocks this chemical space for further pharmacological and insecticidal studies. [Figure not available: see fulltext.]
Author
Jiufu Qin
Technical University of Denmark (DTU)
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Anastasia Krivoruchko
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Boyang Ji
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
BioInnovation Institute
Technical University of Denmark (DTU)
Yu Chen
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
M. Kristensen
Technical University of Denmark (DTU)
Emre Özdemir
Technical University of Denmark (DTU)
J.D. Keasling
University of California
Shenzhen Institutes for Advanced Technologies
Lawrence Berkeley National Laboratory
Joint BioEnergy Institute, California
Technical University of Denmark (DTU)
M. K. Jensen
Technical University of Denmark (DTU)
Jens B Nielsen
Technical University of Denmark (DTU)
BioInnovation Institute
Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology
Beijing University of Chemical Technology
Nature Catalysis
25201158 (eISSN)
Vol. 4 6 498-509Subject Categories
Other Mechanical Engineering
Organic Chemistry
Computer Systems
Infrastructure
Chalmers Infrastructure for Mass spectrometry
DOI
10.1038/s41929-021-00631-z