2012
DOI: 10.1039/c2np00001f
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The generation of “unNatural” products: Synthetic biology meets synthetic chemistry

Abstract: Natural product analogue generation is important, providing tools for chemical biology, enabling structure activity relationship determination and insight into the way in which natural products interact with their target biomolecules. The generation of analogues is also often necessary in order to improve bioavailability and to fine tune compounds' activity. This review provides an overview of the catalogue of approaches available for accessing series of analogues. Over the last few years there have been major… Show more

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Cited by 93 publications
(66 citation statements)
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References 69 publications
(62 reference statements)
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“…Second, these unnatural metabolites, which may be otherwise difficult to obtain, contribute to the expansion of chemical space around privileged scaffolds. 59 Moreover, these new biosynthetic products may address some perceived challenges to the screening of natural products, 60 such as legal access to biodiversity, identification of biological activity, and most recently, intellectual property associated with composition of matter patents, 60,61 which many would consider the most desirable of “Orange Book” patents. 62 In short, this approach imparts another way to translate natural products discoveries into further development.…”
Section: Resultsmentioning
confidence: 99%
“…Second, these unnatural metabolites, which may be otherwise difficult to obtain, contribute to the expansion of chemical space around privileged scaffolds. 59 Moreover, these new biosynthetic products may address some perceived challenges to the screening of natural products, 60 such as legal access to biodiversity, identification of biological activity, and most recently, intellectual property associated with composition of matter patents, 60,61 which many would consider the most desirable of “Orange Book” patents. 62 In short, this approach imparts another way to translate natural products discoveries into further development.…”
Section: Resultsmentioning
confidence: 99%
“…Recently, methods and concepts of organic synthesis have begun to be integrated to synthetic biology to generate novel natural product derivatives. Such approaches that merge biotechnology with organic synthesis are rapidly blooming and are expected to efficiently generate novel natural product analogs in the near future (Goss et al, 2012; Kirschning and Hahn, 2012). A representative example of such an approach has been the use of an Actinosynnema pretiosum mutant that accepts 3-amino-4-bromobenzoic acid as a substrate to prepare pharmacologically active ansamitocin derivatives, which can then be transformed by classical organic reactions (Scheme 4; Taft et al, 2008).…”
Section: Biotechnology-based Generation Of Novel Natural Productsmentioning
confidence: 99%
“…Moreover, by combining the synthetic chemistry and biosynthetic approaches, the access to libraries of synthetically intractable analogs has been permitted (Goss et al, 2012). The methods for in situ cultivations in artificial iChip devices that mimic their natural environment enabled isolation of a new antibiotics teixobactin, without detectable resistance (Ling et al, 2015).…”
Section: Rational Contribution From Synthetic Chemistrymentioning
confidence: 99%