Natural Product Biosynthesis

Natural products with the potential to be used in drug therapy and for agricultural purposes, are a highly sought-after commodity. A famous historic example being penicillin, which has saved millions of lives. With the recent headline problems facing humanity – such as viral pandemics, antimicrobial resistance, food security, and ageing societies – there has never been a more important time to explore natural solutions to global problems.

We are specifically interested in the following areas:

  • Awakening "silent" biosynthetic gene clusters (BGCs) using Streptomyces and cell-free TX-TL expression

  • Capturing "BGCs"

  • Development of Streptomyces venezuelae as a synthetic biology host

  • Studying enzyme function

  • Total enzyme biosynthesis

Past research - Tetrapyrrole BiosynthesisDr Simon Moore also studied and elucidated the biosynthesis of two key tetrapyrroles, under Professor Martin Warren, including the biosynthesis of vitamin B12, which has one of the most complex enzyme pathways (~30 steps) known in natural product biosynthesis.

Elucidation of the anaerobic biosynthesis of vitamin B12 - Moore et al, PNAS 2013;110:14906-11­­. Vitamin B12 is a vital molecule for higher eukaryotes, but is made bacteria. Dr Moore and Prof Warren solved the complex anaerobic biosynthesis of vitamin B12, using a cell-free enzyme approach. This BBSRC funded PhD research was a remarkable feat, considering the highly oxygen sensitive nature of its biosynthetic intermediates, and the intrinsically slow turnover rate, for most of the pathway enzymes. The biosynthetic pathway (10 enzymes) had remained elusive to a number of research groups since its discovery in the 1980s.

Elucidation of coenzyme F430 Biosynthesis - Moore SJ et al, Nature 2017;543:78-82

Coenzyme F430 is a crucial life molecule for the process of methanogenesis, which captures or produces methane - a critical molecule in global warming. Dr Moore as a PDRA (BBSRC funded - BB/I012079/1) and colleagues solved coenzyme F430 biosynthesis, using cell-free enzyme systems to elucidate five novel enzymes (CfbA, -B, -C, -D and -E) that take part in a range of highly oxygen-sensitive reactions.

This research was originally presented by Prof. Gunhild Layer, a key collaborator, at the Chemistry and Biology of Tetrapyrroles Gordon Research Conference (GRC), July 2016.