Design of a self-sufficient hydride-shuttling cascade for concurrent bioproduction of 7,12-dioxolithocholate andl-tert-leucine

Abstract

Oxidoreductase-mediated biotransformation often requires consumption of a secondary sacrificial co-substrate and an additional auxiliary enzyme to drive the cofactor regeneration, which results in generation of unwanted by-product. Herein, we report...

Enzymatic Oxy‐ and Amino‐Functionalization in Biocatalytic Cascade Synthesis: Recent Advances and Future Perspectives

“…Tert-L-leucine (127), a building block for synthesizing relevant antiviral and antitumor drugs, was produced simultaneously with another chiral intermediate of steroidal drugs, 7,12-dioxolithocholic acid (125), in a two-enzymatic whole-cell cascade (Scheme 8y). [192] The first step involved double oxidation of cholic acid (124) in positions 7 and 12 catalyzed by two specific dehydrogenases (7α-HSDH and 12α-HSDH). Both dehydrogenases need NAD + as a cofactor.…”

“…Whole‐cell biocatalysts can also be employed in amino acid synthesis, which is more cost‐effective than their in vitro counterparts, especially when expensive cofactors and cofactor recycling systems are involved. Tert ‐L‐leucine ( 127 ), a building block for synthesizing relevant antiviral and antitumor drugs, was produced simultaneously with another chiral intermediate of steroidal drugs, 7,12‐dioxolithocholic acid ( 125 ), in a two‐enzymatic whole‐cell cascade (Scheme 8y) [192] . The first step involved double oxidation of cholic acid ( 124 ) in positions 7 and 12 catalyzed by two specific dehydrogenases (7α‐HSDH and 12α‐HSDH).…”

Machine-Learning-Guided Engineering of an NADH-Dependent 7β-Hydroxysteroid Dehydrogenase for Economic Synthesis of Ursodeoxycholic Acid

“…Alternatively, chemically synthesized UDCA can be produced from cholic acid (CA) or chenodeoxycholic acid (CDCA) . However, chemical synthesis often requires multiple protection and deprotection steps, resulting in low/moderate overall yields, and the inevitable use of hazardous and toxic reagents generates large amounts of waste, showing increased environmental burden of industrial manufacture. − Therefore, studies on the enzymatic synthesis of UDCA have attracted great attention due to the mild reaction conditions and eco-friendly nature of enzymatic reactions. − …”

An Artificial Pathway for N-Hydroxy-Pipecolic Acid Production From L-Lysine in Escherichia coli

“…Recently, many important useful chemicals, such as ectoine ( Zhang S. et al, 2021 ), itaconic acid ( Elmore et al, 2021 ), naringenin ( Zhang Q. et al, 2021 ), ε-caprolactone ( Xiong et al, 2021 ), curcuminoids ( Rodrigues et al, 2020 ), cadaverine ( Ting et al, 2021 ), 5-hydroxyvaleric acid ( Sohn et al, 2021 ), tyrian purple ( Lee et al, 2021 ), 1,5-pentanediol ( Cen et al, 2021 ), isobutanol ( Yu et al, 2019 ), and pyruvic acid ( Luo et al, 2020 ) have been obtained in microorganisms. There are many effective strategies that have been developed and used to improve the production of target chemicals, such as enzyme engineering ( Ting et al, 2021 ), cofactor engineering ( You et al, 2021 ), transcription factor engineering ( Kang et al, 2021 ), promoter engineering ( Gao et al, 2020 ), modularity engineering ( Cen et al, 2021 ; Osire et al, 2021 ), ribosome binding site engineering ( Wang et al, 2018 ), pathway engineering ( Wang et al, 2021 ), fine-tuning gene expression ( Wang et al, 2015 ), biosensor technology ( Li et al, 2019 ), high-through screening ( Zeng et al, 2020 ), and so on.…”