Modular optimization of multi-gene pathways for fatty acids production in E. coli

Peng Xu, Qin Gu, Wenya Wang, Lynn Wong, Adam G.W. Bower, Cynthia H. Collins, Mattheos A.G. Koffas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

405 Scopus citations


Microbial fatty acid-derived fuels have emerged as promising alternatives to petroleum-based transportation fuels. Here we report a modular engineering approach that systematically removed metabolic pathway bottlenecks and led to significant titre improvements in a multi-gene fatty acid metabolic pathway. On the basis of central pathway architecture, E. coli fatty acid biosynthesis was re-cast into three modules: the upstream acetyl coenzyme A formation module; the intermediary acetyl-CoA activation module; and the downstream fatty acid synthase module. Combinatorial optimization of transcriptional levels of these three modules led to the identification of conditions that balance the supply of acetyl-CoA and consumption of malonyl-CoA/ACP. Refining protein translation efficiency by customizing ribosome binding sites for both the upstream acetyl coenzyme A formation and fatty acid synthase modules enabled further production improvement. Fed-batch cultivation of the engineered strain resulted in a final fatty acid production of 8.6 g l-1. The modular engineering strategies demonstrate a generalized approach to engineering cell factories for valuable metabolites production.

Original languageEnglish
Article number1409
JournalNature Communications
StatePublished - 2013
Externally publishedYes


Dive into the research topics of 'Modular optimization of multi-gene pathways for fatty acids production in E. coli'. Together they form a unique fingerprint.

Cite this