Citation

BibTex format

@article{Peng:2023:10.1021/acssynbio.3c00047,
author = {Peng, H and Chen, R and Shaw, WM and Hapeta, P and Jiang, W and Bell, DJ and Ellis, T and Ledesma-Amaro, R},
doi = {10.1021/acssynbio.3c00047},
journal = {ACS Synthetic Biology},
pages = {1739--1749},
title = {Modular metabolic engineering and synthetic coculture strategies for the production of aromatic compounds in yeast},
url = {http://dx.doi.org/10.1021/acssynbio.3c00047},
volume = {12},
year = {2023}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - Microbial-derived aromatics provide a sustainable and renewable alternative to petroleum-derived chemicals. In this study, we used the model yeast Saccharomyces cerevisiae to produce aromatic molecules by exploiting the concept of modularity in synthetic biology. Three different modular approaches were investigated for the production of the valuable fragrance raspberry ketone (RK), found in raspberry fruits and mostly produced from petrochemicals. The first strategy used was modular cloning, which enabled the generation of combinatorial libraries of promoters to optimize the expression level of the genes involved in the synthesis pathway of RK. The second strategy was modular pathway engineering and involved the creation of four modules, one for product formation: RK synthesis module (Mod. RK); and three for precursor synthesis: aromatic amino acid synthesis module (Mod. Aro), p-coumaric acid synthesis module (Mod. p-CA), and malonyl-CoA synthesis module (Mod. M-CoA). The production of RK by combinations of the expression of these modules was studied, and the best engineered strain produced 63.5 mg/L RK from glucose, which is the highest production described in yeast, and 2.1 mg RK/g glucose, which is the highest yield reported in any organism without p-coumaric acid supplementation. The third strategy was the use of modular cocultures to explore the effects of division of labor on RK production. Two two-member communities and one three-member community were created, and their production capacity was highly dependent on the structure of the synthetic community, the inoculation ratio, and the culture media. In certain conditions, the cocultures outperformed their monoculture controls for RK production, although this was not the norm. Interestingly, the cocultures showed up to 7.5-fold increase and 308.4 mg/L of 4-hydroxy benzalacetone, the direct precursor of RK, which can be used for the semi-synthesis of RK. This study illustrates the utility of modularity in synth
AU - Peng,H
AU - Chen,R
AU - Shaw,WM
AU - Hapeta,P
AU - Jiang,W
AU - Bell,DJ
AU - Ellis,T
AU - Ledesma-Amaro,R
DO - 10.1021/acssynbio.3c00047
EP - 1749
PY - 2023///
SN - 2161-5063
SP - 1739
TI - Modular metabolic engineering and synthetic coculture strategies for the production of aromatic compounds in yeast
T2 - ACS Synthetic Biology
UR - http://dx.doi.org/10.1021/acssynbio.3c00047
UR - https://www.ncbi.nlm.nih.gov/pubmed/37218844
UR - https://pubs.acs.org/doi/10.1021/acssynbio.3c00047
UR - http://hdl.handle.net/10044/1/104787
VL - 12
ER -