Rational pathway engineering of type I fatty acid synthase allows the biosynthesis of triacetic acid lactone from D-glucose in vivo.
Metabolic pathway engineering is a powerful tool to synthesize structurally diverse and complex chemicals via genetic manipulation of multistep catalytic systems involved in cell metabolism. Here, we report the rational design of a fatty acid biosynthetic pathway, Brevibacterium ammoniagenes fatty acid synthase B (FAS-B), that allows the microbial synthesis of triacetic acid lactone (TAL) from an inexpensive feedstock, d-glucose. TAL can be chemically converted to phloroglucinol, which is a core structure for the synthesis of various high value bioactive compounds and energetic compounds such as 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Synthesis of phloroglucinol from d-glucose using this combined biological and chemical synthesis may offer significant advantages over the current phloroglucinol manufacture, including environmental friendliness and reduction in the cost of phloroglucinol. More importantly, it represents a novel strategy for the benzene-free synthesis of aromatic chemicals.
Zha
Wenjuan
W
Department of Chemical and Biomolecular Engineering, University of Illinois, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Shao
Zengyi
Z
Frost
John W
JW
Zhao
Huimin
H
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001951:Brevibacterium / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D011753:Pyrones / Q000378:metabolism*
D001426:Bacterial Proteins; D011753:Pyrones; C030720:triacetic acid lactone; D064429:Fatty Acid Synthases; C413881:fatty acid synthase I, mycobacteria; D005947:Glucose