Abstract
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.].
| Original language | English |
|---|---|
| Journal | Nature Catalysis |
| Volume | 4 |
| Issue number | 6 |
| Pages (from-to) | 498-509 |
| DOIs | |
| Publication status | Published - 2021 |
Bibliographical note
Funding Information:This work was funded by the Novo Nordisk Foundation (NNF10CC1016517), the Swedish Foundation for Strategic Research and the Knut and Alice Wallenberg Foundation. We thank J. Zhang, I. Borodina and Q-L. Liu for helpful discussions, J. Zhang for kindly providing plasmids from the CRISPR/Cas9 genome editing system, Q-L. Liu and Y. Chen for kindly providing aromatic chemical overproducing strains, A. Hoffmeyer for genome sequencing, M. Gossing, D. Romero-Suarez, the Chalmers Mass Spectrometry Infrastructure and the Analytical Core Facility of the Novo Nordisk Foundation Center for Biosustainability at Technical University of Denmark for assistance with metabolite analysis.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
