Biology subjects

Moore, S. J.

Publications and source records attributed to Moore, S. J..

2 recordsLinked to original sources

bioRxiv2017

A semi-synthetic strategy for derivatization of the violacein natural product scaffold

Natural products and their analogues are often challenging to synthesise due to their complex scaffolds and embedded functional groups. Solely relying on engineering the biosynthesis of natural products may lead to limited compound diversity. Integrating synthetic biology with synthetic chemistry allows rapid access to much more diverse portfolios of xenobiotic compounds which may accelerate the discovery of new therapeutics. As a proof-of-concept, by supplementing an Escherichia coli strain expressing the violacein biosynthesis pathway with 5-bromo-tryptophan in vitro or tryptophan 7-halogenase RebH in vivo, 6 halogenated analogues of violacein or deoxyviolacein were generated, demonstrating promiscuity of the violacein biosynthesis pathway. Furthermore, 20 new derivatives were generated from 5-brominated violacein analogues via Suzuki-Miyaura cross-coupling reaction directly using the crude extract without prior purification. Herein, we demonstrate a flexible and rapid approach to access diverse chemical space that can be applied to a wide range of natural product scaffolds.

synthetic biology↗

bioRxiv2017

A cell-free synthetic biochemistry platform for raspberry ketone production

Cell-free synthetic biochemistry provides a green solution to replace traditional petroleum or agricultural based methods for production of fine chemicals. 4-(4-hydroxyphenyl)-butan-2-one, also known as raspberry ketone, is the major fragrance component of raspberry fruit and is utilised as a natural additive in the food and sports industry. Current industrial processing standards involve chemical extraction with a yield of 1-4 mg per kilo of fruit. As such its market price can fluctuate up to $20,000 per kg. Metabolic engineering approaches to synthesise this molecule by microbial fermentation have only resulted in low yields of up to 5 mg L-1. In contrast, cell-free synthetic biochemistry offers an intriguing compromise to the engineering constraints provided by the living cell. Using purified enzymes or a two-step semisynthetic route, an optimised pathway was formed for raspberry ketone synthesis leading up to 100% yield conversion. The semi-synthetic route is potentially scalable and cost-efficient for industrial synthesis of raspberry ketone.

synthetic biology↗