Cascade Biocatalysis for Sustainable Asymmetric Synthesis: From Biobased l‐Phenylalanine to High‐Value Chiral Chemicals

Abstract

Sustainable synthesis of useful and valuable chiral fine chemicals from renewable feedstocks is highly desirable but remains challenging. Reported herein is a designed and engineered set of unique non-natural biocatalytic cascades to achieve the asymmetric synthesis of chiral epoxide, diols, hydroxy acid, and amino acid in high yield and with excellent ee values from the easily available biobased l-phenylalanine. Each of the cascades was efficiently performed in one pot by using the cells of a single recombinant strain over-expressing 4-10 different enzymes. The cascade biocatalysis approach is promising for upgrading biobased bulk chemicals to high-value chiral chemicals. In addition, combining the non-natural enzyme cascades with the natural metabolic pathway of the host strain enabled the fermentative production of the chiral fine chemicals from glucose.

One‐Pot Production of Natural 2‐Phenylethanol from L‐Phenylalanine via Cascade Biotransformations

“…AtPAL2 and AnPAD (fdc1 and pad1) genes had been cloned together in compatible plasmid to give the first module (PAL_PAD). [19] To engineer the second module, SMO genes (styAB), SOI gene (styC) and PAR gene had been engineered together with SMO_SOI to give SMO_SOI_PAR. To obtain balanced enzyme expression in the E. coli strains, many strategies could be employed, such as engineering the promoters [20] or the ribosome-binding sites [21] of the genes.…”

Bi‐enzymatic Conversion of Cinnamic Acids to 2‐Arylethylamines

“…Initially, changing the ammonia concentration for the cascade reaction to 1000 mM (to favour the first step) and 250 mM (to favour the second step) both resulted in lower levels of the amine ( Table 2, entries 1-3). As such, 500 mM was used as a compromise with the pH either increased or decreased to favour each step in turn ( Table 2, entries [4][5][6]. This resulted in a slight improvement at the more acidic pH and extremely poor yield of 3 a at the more basic pH.…”

Easy Access to Enantiopure (S)‐ and (R)‐Aryl Alkyl Alcohols by a Combination of Gold(III)‐Catalyzed Alkyne Hydration and Enzymatic Reduction

“…[1][2][3] In this regard, the combination of several reaction steps within one poti sa na ttractive strategy,a st he number of workup and purification steps can be substantially reduced. [4][5][6][7][8][9] During the past decades, biocatalysis was established as ah ighly potent method for the introductiona nd manipulation of stereochemistry,i n particularo nt he basis of improved access to versatile enzymes of naturalo rigin or by enzyme engineering. [10][11][12][13][14][15] Linking enzyme-mediated reactions with metal-assisted catalysis is generallyu nderstooda sahighly prospective approach, as both areas offer complementary functional group interconversions.…”