Natural products via enzymatic reactions
01 Jan 2010-Vol. 297
TL;DR: Key Building Blocks via Enzyme-Mediated Synthesis via Enzymatic and Chemoenzymatic Synthesis of Carbohydrate Containing Natural Products are presented.
Abstract: Key Building Blocks via Enzyme-Mediated Synthesis.- Engineered Biosynthesis of Plant Polyketides: Structure-Based and Precursor-Directed Approach.- Enzymatic and Chemo-Enzymatic Approaches Towards Natural and Non-Natural Alkaloids: Indoles, Isoquinolines, and Others.- Chemoenzymatic and Bioenzymatic Synthesis of Carbohydrate Containing Natural Products.- Total (Bio)Synthesis: Strategies of Nature and of Chemists.
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TL;DR: A fully automated process for enzyme-mediated oligosaccharide synthesis that can give easy access to different classes of complex glycans including poly-N-acetyllactosamine derivatives, human milk oligOSaccharides, gangliosides and N-glycans is reported.
Abstract: An automated platform that can synthesize a wide range of complex carbohydrates will greatly increase their accessibility and should facilitate progress in glycoscience. Here we report a fully automated process for enzyme-mediated oligosaccharide synthesis that can give easy access to different classes of complex glycans including poly-N-acetyllactosamine derivatives, human milk oligosaccharides, gangliosides and N-glycans. Our automated platform uses a catch and release approach in which glycosyltransferase-catalysed reactions are performed in solution and product purification is accomplished by solid phase extraction. We developed a sulfonate tag that can easily be installed and enables highly efficient solid phase extraction and product release using a single set of washing conditions, regardless of the complexity of the glycan. Using this custom-built synthesizer, as many as 15 reaction cycles can be performed in an automated fashion without a need for lyophilization or buffer exchange steps.
102 citations
TL;DR: The site-selective bromination of vancomycin is reported to produce, with substantial efficiency, previously unknown monobromovancomycins, a dibromovan comycin, and a tribromovancycin.
Abstract: We report the site-selective bromination of vancomycin to produce, with substantial efficiency, previously unknown monobromovancomycins, a dibromovancomycin, and a tribromovancomycin. We document the inherent reactivity of native vancomycin toward N-bromophthalimide. We then demonstrate significant rate acceleration and perturbation of the inherent product distribution in the presence of a rationally designed peptide-based promoter. Alternative site selectivity is observed as a function of solvent and replacement of the peptide with guanidine.
96 citations
TL;DR: In this review, cytochrome P450 enzymes were proven to extend the synthetic toolbox significantly by adding to the flexibility and efficacy of synthetic strategies of natural product chemists, and scientists of other related disciplines.
Abstract: The biological potency of natural products has been exploited for decades. Their inherent structural complexity and natural diversity might hold the key to efficiently address the urgent need for the development of novel pharmaceuticals. At the same time, it is that very complexity, which impedes necessary chemical modifications such as structural diversification, to improve the effectiveness of the drug. For this purpose, Cytochrome P450 enzymes, which possess unique abilities to activate inert sp3-hybridised C-H bonds in a late-stage fashion, offer an attractive synthetic tool. In this review the potential of cytochrome P450 enzymes in chemoenzymatic lead diversification is illustrated discussing studies reporting late-stage functionalisations of natural products and other high-value compounds. These enzymes were proven to extend the synthetic toolbox significantly by adding to the flexibility and efficacy of synthetic strategies of natural product chemists, and scientists of other related disciplines.
60 citations
TL;DR: Coupling genetic code expansion (GCE) with metabolic engineering is the basic prerequisite to transform orthogonal translation from a standard technique in academic research to industrial biotechnology.
46 citations
Cites background from "Natural products via enzymatic reac..."
...Moreover, novel pathways can be created by modular combination of enzymes that catalyse desired chemical reactions [13]....
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TL;DR: This review discusses recent examples from three areas: polyketide catalytic domain engineering geared toward synthesis of new polyketides, engineering of tailoring enzymes (other than oxidative enzymes) as biocatalysts, and in vitro total synthesis of natural products using purified enzyme components.
Abstract: Natural products are important sources of pharmaceuticals, in part owing to their diverse biological activities. Enzymes from natural product biosynthetic pathways have become attractive candidates as biocatalysts for modifying the structures and bioactivities of these complex compounds. Numerous enzymes have been harvested to generate innovative scaffolds, large-scale synthesis of chiral building blocks, and semisynthesis of medicinally relevant natural product derivatives. This review discusses recent examples from three areas: (a) polyketide catalytic domain engineering geared toward synthesis of new polyketides, (b) engineering of tailoring enzymes (other than oxidative enzymes) as biocatalysts, and (c) in vitro total synthesis of natural products using purified enzyme components. With the availability of exponentially increasing genomic information and new genome mining tools, many new and powerful biocatalysts tailored for pharmaceutical synthesis will likely emerge from secondary metabolism.
42 citations
Cites background from "Natural products via enzymatic reac..."
...An alternate approach to overcome the problems associated with in vivo biosynthesis is enzymatic total synthesis of complex biomolecules (108)....
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