Engineering yeast metabolism for the discovery and production of polyamines and polyamine analogues
Artikel i vetenskaplig tidskrift, 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.]
Författare
Jiufu Qin
Danmarks Tekniske Universitet (DTU)
Chalmers, Biologi och bioteknik, Systembiologi
Anastasia Krivoruchko
Chalmers, Biologi och bioteknik, Systembiologi
Boyang Ji
Chalmers, Biologi och bioteknik, Systembiologi
BioInnovation Institute
Danmarks Tekniske Universitet (DTU)
Yu Chen
Chalmers, Biologi och bioteknik, Systembiologi
M. Kristensen
Danmarks Tekniske Universitet (DTU)
Emre Özdemir
Danmarks Tekniske Universitet (DTU)
J.D. Keasling
University of California
Shenzhen Institutes for Advanced Technologies
Lawrence Berkeley National Laboratory
Joint BioEnergy Institute, California
Danmarks Tekniske Universitet (DTU)
M. K. Jensen
Danmarks Tekniske Universitet (DTU)
Jens B Nielsen
Danmarks Tekniske Universitet (DTU)
BioInnovation Institute
Chalmers, Biologi och bioteknik, Systembiologi
Beijing University of Chemical Technology
Nature Catalysis
25201158 (eISSN)
Vol. 4 6 498-509Ämneskategorier
Annan maskinteknik
Organisk kemi
Datorsystem
Infrastruktur
Chalmers infrastruktur för masspektrometri
DOI
10.1038/s41929-021-00631-z