The aromatic amino acid biosynthetic pathway of E. coli was engineered to produce versatile building blocks for fine chemicals synthesis by fermentation.

The natural key intermediate in the aromatic amino acid biosynthetic pathway is chorismate, a starting point for diverging pathways to the aromatic amino acids as well as to enterobactin, folate, ubiquinone, and menaquinone.

Elaborating on this natural example, combinations of gene deletion and amplification were used to rationally construct E.coli strains capable of high-level production of functionalized cyclohexadiene-trans-diols (1, 2). In contrast to the corresponding cis-compounds, these trans-diols have not been readily available before.

The potential of compounds 1 and 2 as chiral building blocks was demonstrated in short and efficient syntheses of biologically active cyclohexane epoxides. Compounds 1 and 2 can also be attractive starting materials in the preparation of many other cyclitols and carbohydrate mimics.

Additional engineering has opened up fermentative routes to aminocyclitols. Starting from the actual fermentation products 3 and 4, a variety of syntheses of stereoisomers of biologically active compounds is possible, including a short and novel route to the neuraminidase inhibitor, oseltamivir (Tamiflu®).

 

1	2		3	4