Design of a dynamic sensor-regulator system for production of chemicals and fuels derived from fatty acids

• Published in: Nature biotechnology Vol. 30; no. 4; pp. 354 - 359
• Main Authors: Zhang, Fuzhong, Carothers, James M, Keasling, Jay D
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.04.2012; Nature Publishing Group
• Subjects: 631/1647/1511; 631/61/338/318; 631/61/350/59; 639/638/224/906; Agriculture; AraC Transcription Factor - genetics; Biodiesel fuels; Biofuel production; Biofuels - microbiology; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedical engineering; Biomedical Engineering/Biotechnology; Biomedicine; Biosensing Techniques - instrumentation; Biosensing Techniques - methods; Biosensors; Biosynthesis; Biotechnology; Chemical synthesis; Chemicals; E coli; Energy; Escherichia coli; Escherichia coli - chemistry; Escherichia coli - growth & development; Fatty acids; Fatty Acids - biosynthesis; Fatty Acids - chemistry; Fundamental and applied biological sciences. Psychology; Industrial applications and implications. Economical aspects; letter; Life Sciences; Production processes; Promoter Regions, Genetic; Sensors; Transcription Factors - chemistry; United States; Regulation(control); Escherichia coli; Production; Bacteria; Metabolic engineering; Biofuel; Gene expression; Transcription factor; Fatty acids; Biodiesel; Enterobacteriaceae
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt.2149

Expressing heterologous pathways in cells can create detrimental metabolic imbalances. Zhang et al . increase the yield of a biofuel by engineering regulators in Escherichia coli that sense and adjust pathway expression based on the presence of key intermediate metabolites. Microbial production of chemicals is now an attractive alternative to chemical synthesis. Current efforts focus mainly on constructing pathways to produce different types of molecules 1 , 2 , 3 . However, there are few strategies for engineering regulatory components to improve product titers and conversion yields of heterologous pathways 4 . Here we developed a dynamic sensor-regulator system (DSRS) to produce fatty acid–based products in Escherichia coli , and demonstrated its use for biodiesel production. The DSRS uses a transcription factor that senses a key intermediate and dynamically regulates the expression of genes involved in biodiesel production. This DSRS substantially improved the stability of biodiesel-producing strains and increased the titer to 1.5 g/l and the yield threefold to 28% of the theoretical maximum. Given the large number of natural sensors available, this DSRS strategy can be extended to many other biosynthetic pathways to balance metabolism, thereby increasing product titers and conversion yields and stabilizing production hosts.