%P 10120-10125 %N 30 %K Biocatalysis, benzylisoquinoline alkaloids, norcoclaurine synthase, enzyme cascades %T Design and use of de novo cascades for new benzylisoquinoline alkaloid biosynthesis %D 2019 %V 58 %L discovery10074317 %I Wiley-VCH Verlag %O This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. %A H Hailes %A J Ward %A Y Wang %A N Tappertzhofen %A D Mendez-Sanchez %A M Bawn %A B Lyu %J Angewandte Chemie %X The benzylisoquinoline alkaloids (BIAs) are an important group of higher plant secondary metabolites, which have been reported to show significant pharmaceutical activities. The production of BIAs via synthetic biology approaches provides a higher yielding strategy compared to traditional synthetic methods and plant isolation methods. However, the reconstruction of BIAs pathways in microorganisms combining heterologous enzymes can also give access to BIAs via cascade reactions. Most importantly, nonâ€natural BIAs can be generated through such artificial pathways. In the current study, we describe new tyrosinases and decarboxylases and combine these with a transaminase enzyme and norcoclaurine synthase for the efficient synthesis of several BIAs, including six nonâ€natural alkaloids, in cascades from Lâ€tyrosine and analogues.