Engineered, highly productive biosynthesis of artificial, lactonized statin side-chain building blocks: The hidden potential of Escherichia coli unleashed

A schematic representation of the artificial pathway for the biosynthesis of the lactonized statin side-chain intermediates. Acetaldehyde (1) and acetyloxy-acetaldehyde (2g) are fed to the engineered E. coli culture. A: Intracellular DERA-catalyzed sequential aldol condensation, optimized to yield 3g. As a side product, 3a is formed at low quantities. B: Transmembrane diffusion of substrates, intermediates and products supports the substrate supply to intracellular DERA and to the periplasmically oriented, PQQ dependent glucose dehydrogenase (Gcd). C: Periplasmic oxidation of DERA-derived lactols to the desired lactones (4g) by the Gcd. D: The respiratory chain transferring the electrons to the oxygen.