Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols.

TitleCompartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols.
Publication TypeJournal Article
Year of Publication2013
AuthorsAvalos, JL, Fink, GR, Stephanopoulos, G
JournalNat Biotechnol
Volume31
Issue4
Pagination335-41
Date Published2013 Apr
ISSN1546-1696
KeywordsAlcohols, Butanols, Cell Compartmentation, Cytoplasm, Fermentation, Genetic Engineering, Metabolic Networks and Pathways, Mitochondria, Pentanols, Saccharomyces cerevisiae, Subcellular Fractions
Abstract

<p>Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in the same pathways in the cytoplasm. Compartmentalization of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overproducing enzymes involved in only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains revealed that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves greater local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion and reducing the loss of intermediates to competing pathways.</p>

DOI10.1038/nbt.2509
Alternate JournalNat. Biotechnol.
PubMed ID23417095
PubMed Central IDPMC3659820
Grant ListF32 GM098022 / GM / NIGMS NIH HHS / United States
GM040266 / GM / NIGMS NIH HHS / United States
1F32GM098022-01A1 / GM / NIGMS NIH HHS / United States
R01 GM040266 / GM / NIGMS NIH HHS / United States
R01 GM085323 / GM / NIGMS NIH HHS / United States
R01 GM035010 / GM / NIGMS NIH HHS / United States