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

BioInnovation Institute

Chalmers, Biologi och bioteknik, Systembiologi

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

Danmarks Tekniske Universitet (DTU)

Lawrence Berkeley National Laboratory

Shenzhen Institutes for Advanced Technologies

Joint BioEnergy Institute, California

M. K. Jensen

Danmarks Tekniske Universitet (DTU)

Jens B Nielsen

BioInnovation Institute

Beijing University of Chemical Technology

Danmarks Tekniske Universitet (DTU)

Chalmers, Biologi och bioteknik, Systembiologi

Nature Catalysis

25201158 (eISSN)

Vol. In Press

Ämneskategorier

Annan maskinteknik

Organisk kemi

Datorsystem

Infrastruktur

Chalmers infrastruktur för masspektrometri

DOI

10.1038/s41929-021-00631-z

Mer information

Senast uppdaterat

2021-06-29