Diversity‐Oriented Production of Metabolites Derived from Chorismate and Their Use in Organic Synthesis

Abstract

Biosynthesis as a model: Based on the branched structure of biosynthetic pathways, such as the shikimate pathway, the selective bioproduction of a set of diverse metabolites has been achieved by means of metabolic engineering (see scheme). A scale‐up for preparative purposes was performed, resulting in high product titers and yields from renewable resources.

β- and σ-Amino acids (2,3- and 3,4-trans-CHA) as catalysts in Knoevenagel condensation and asymmetric aldol reactions

“…Amino acids and 1,2-diol metabolites derived from chorismic acid (1) as a branching point. 33 Compounds 2 and 4 are metabolites of the shikimate biosynthetic pathway (Scheme 1). Microbial access to 2 was realized by heterologous expression of phzDE in E. coli cells, which allowed the production of up to 12 g·L -1 of 2.…”

“…Microbial access to 2 was realized by heterologous expression of phzDE in E. coli cells, which allowed the production of up to 12 g·L -1 of 2. 33,43 By using a 300-L fed-batch culture approach, 2 was produced on a kg scale. 44 Isolation of 2 was performed by concentration of the cell-free fermentation broth and crystallization from water at 4 °C.…”

“…[30][31][32] We were intrigued by the idea of using nonproteinogenic, yet natural, primary β-and δ-amino acids as catalysts. (5S,6S)-6-Amino-5-hydroxycyclohexa-1,3-dienecarboxylic acid (2,3-trans-CHA, 2) and (3R,4R)-4-amino-3-hydroxycyclohexa-1,5-dienecarboxylic acid (3,4-trans-CHA, 4) (Scheme 1) are nonproteinogenic primary amino acid metabolites of the shikimate pathway 33 and are accessible through metabolic engineering of recombinant E. coli strains. 34 The shikimate pathway is an instructive example of diversity-oriented biosynthesis of a wide spectrum of natural products (Scheme 1).…”

New Stetter reactions catalyzed by thiamine diphosphate dependent MenD from E. coli

“…Nevertheless, the common basic mechanism of the 1,4-additions catalyzed by MenD and the stetterases warranted a closer examination of the substrate range of the MenD-catalyzed Stetter reactions. Moreover, MenD was selected by us because of its promising application in biotechnological processes (Bongaerts et al, 2011): its donor substrate ␣-ketoglutarate is derived from the central metabolism and MenD can thus be used advantageously in in vivo transformations for the diversity-oriented production of building blocks for organic synthesis.…”

Hydroxy-L-prolines as asymmetric catalysts for aldol, Michael addition and Mannich reactions

“…Recently, Müller et al published results of aldol reactions using a Zn-complex of some chorismate metabolites such as trans-2,3-CHA and trans-3,4-CHA which showed high enantioselectivity in the aldol addition. 52,53 Hüttel et al studied the influence of hydroxyproline derivatives and some other non-proteinogenic amino acids on the aldol addition and on Michael and Mannich reactions.…”