Access to natural products and their analogues is crucial. Such compounds have, for many years, played a central role in the area of drug discovery as well as in providing tools for chemical biology. The ability to quickly and inexpensively acquire genome sequences has accelerated the field of natural product research. Access to genomic data coupled with new technologies for the engineering of organisms is resulting in the identification of large numbers of previously undiscovered natural products as well as an increased understanding of how the biosynthetic pathways responsible for the biogenesis of these compounds may be manipulated. This short review summarizes and reflects upon approaches to accessing natural products and has a particular focus on approaches combining molecular biology and synthetic chemistry.
Mahoney KPP, Smith DRM, Bogosyan EJA, Goss RJM
Synthesis 2014, 46 (16), 2122
A simple and scalable one-pot biotransformation enables direct access to l-halotryptophans, including l-7-iodotryptophan, from the corresponding haloindoles. The biotransformation utilizes an easy to prepare bacterial cell lysate that may be stored as the lyophilizate for several months and utilized as a catalyst as and when required.
Smith, DRM, Willemse T, Gkotsi DS, Schepens W, Maes BU, Ballet S, Goss RJM
Org Lett 2014, 16 (10) 2622-2625
Smith DRM; Grüschow S; Goss RJM
Curr Opin Chem Biol 2012, 17 (2) 276-283
A large and diverse series of halogenated natural products exist. In many of these compounds the halogen is important to biological activity and bioavailability. We now recognise that nature has developed many different halogenation strategies for which well-known enzyme classes such as haem oxidases or flavin-dependent oxidases have been adapted. Enzymes capable of halogenating all kinds of different chemical groups from electron-rich to electron-poor, from aromatic to aliphatic have been characterised. Given that synthetic halogenation reactions are not trivial transformations and that halogenated molecules possess pharmaceutical usefulness, it will be worth investing into further research of halogenating enzymes.