Hailes, H; Ward, J; Wang, Y; Tappertzhofen, N; Mendez-Sanchez, D; Bawn, M; Lyu, B; (2019) Design and use of de novo cascades for new benzylisoquinoline alkaloid biosynthesis. Angewandte Chemie , 58 (30) pp. 10120-10125. 10.1002/anie.201902761.

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Abstract

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, non‐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 non‐natural alkaloids, in cascades from L‐tyrosine and analogues.

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