Artificial Biocatalytic Linear Cascades for Preparation of Organic Molecules

Abstract

The review compiles artificial cascades involving enzymes with a focus on the last 10 years. A cascade is defined as the combination of at least two reaction steps in a single reaction vessel without isolation of the intermediates, whereby at least one step is catalyzed by an enzyme. Additionally, cascades performed in vivo and in vitro are discussed separately, whereby in vivo cascades are defined here as cascades relying on cofactor recycling by the metabolism or on a metabolite from the living organism. The review introduces a systematic classification of the cascades according to the number of enzymes in the linear sequence and differentiates between cascades involving exclusively enzymes and combinations of enzymes with non-natural catalysts or chemical steps. Since the number of examples involving two enzymes is predominant, the two enzyme cascades are further subdivided according to the number, order, and type of redox steps. Furthermore, this classification differentiates between cascades where all reaction steps are performed simultaneously, sequentially, or in flow.

Simultaneous Enzyme/Whole‐Cell Biotransformation of C18 Ricinoleic Acid into (R)‐3‐Hydroxynonanoic Acid, 9‐Hydroxynonanoic Acid, and 1,9‐Nonanedioic Acid

“…[1] For instance, the engineered whole-cell based biocatalysis permitted the production of a variety of chemicals including medium chain w-hydroxycarboxylic acids, a,w-dicarboxylic acids, and w-aminocarboxylic acids from renewable oils and fatty acids. [1] For instance, the engineered whole-cell based biocatalysis permitted the production of a variety of chemicals including medium chain w-hydroxycarboxylic acids, a,w-dicarboxylic acids, and w-aminocarboxylic acids from renewable oils and fatty acids.…”

Enzyme Cascade Reactions for the Biosynthesis of Long Chain Aliphatic Amines from Renewable Fatty Acids

“…Scheme 2. The V. fluvialis ATA (VF-ATA) variants (i. e., H1_ R (triple mutant of VF-ATA (L56V, W57F, F85V)) (A), H3_ RA (triple mutant of VF-ATA (L56V, W57C, V153A)) (B), and H3_RAV (quadruple mutant of VF-ATA (L56V, W57C, F85V, V153A)) (C) were used for amination of (Z)-12ketooctadec-9-enoic acid (2). Oleic acid (4) is converted into 10-aminooctadecanoic acid (7) via 10hydroxyoctadecanoic acid (5) and 10-keto-octadecanoic acid (6).…”

Regulating Transition Metal Catalysis Through Interference by Short RNAs

“…[1] Protein enzymes,u tilized in isolated form, [2,3] as part of constructed artificial pathways, [4,5] or encapsulated within cells programmed to express them, [6,7] often form reaction products efficiently and stereoselectively under mild conditions.W hile many of the recently developed biocatalytic transformations are mechanistically similar to native biochemical processes,s everal reported systems feature distinctly abiotic transformations,w here the products of the reactions arise through am echanism hitherto unknown in biology.E xamples include Ru-catalyzed olefin metathesis reactions in the artificial active site of an evolved streptavidin protein [8] and Ir-a nd Fe-catalyzed metal carbenoid and nitrenoid insertion reactions from evolved P450 enzymes. Further development of this catalytic system will expand not only the chemical space available to synthetic biological systems but also allow for temporal and spatial control of transition-metal catalysis through gene transcription.…”