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Dr

Simon Moore

Associate Professor

Department of Life Sciences - Faculty of Natural Sciences

Orcid identifier0000-0002-1968-206X
  • Associate Professor
    Department of Life Sciences - Faculty of Natural Sciences

RESEARCH

Moore Group research website - www.mooresynbio.com

 

Natural Product Biosynthesis & Engineering

Microbes harbour extraordinary potential to produce complex chemicals encoded within biosynthetic gene clusters (BGCs), yet most remain silent or inactive under laboratory conditions. Our group develops strategies to unlock these dormant pathways through synthetic biology, targeting applications that address critical global challenges: combating antimicrobial resistance, protecting crops sustainably, and replacing petrochemical synthesis routes with biological alternatives. We specialise in engineering Streptomyces venezuelae, a fast-growing model organism with proven industrial uses, to activate silent BGCs and produce novel bioactive compounds for pharmaceutical and agricultural applications.

We also study biosynthetic pathways containing promiscuous enzymes that recognise non-natural substrates, extending beyond single enzyme studies to complex multistep pathways. Our work encompasses enzyme discovery, pathway engineering, and the production of high-value chemicals, and novel biotherapeutics for therapeutic and industrial applications. We use synthetic biology tools including CRISPR-Cas9 and heterologous hosts for activating silent BGCs, unlocking nature's hidden chemical diversity for pharmaceutical and agrochemical applications.

  Selected Publications:
  • Hung-En Lai, Agata Kennedy, Lewis Tanner, Emma A. Bartram, Soo Mei Chee, Paul S. Freemont, Simon J. Moore. Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712. ChemBioChem (2024) 25:e202400357
  • Hung-En Lai, Alan M. C. Obled, Soo Mei Chee, Rhodri M. Morgan, Rosemary Lynch, Sunil V. Sharma, Simon J. Moore, Karen M. Polizzi, Rebecca J. M. Goss, and Paul S. Freemont. A GenoChemetic strategy for derivatisation of the violacein natural product scaffold. ACS Chemical Biology (2021) 16(11):2116

 

Cell-free Synthetic Biology

We pioneer the development of high-yielding cell-free expression systems for academic and industrial purposes, creating extracts from diverse bacteria and optimising systems to achieve high peptide/protein yields (up to 4 mg/mL). Cell-free systems are part of a growing area of research, with a broad variety of applications (e.g., high-value peptides/proteins, high-throughput screening, biosensors, and flexible engineering of pathways). One of key advantages of cell-free is its capability with high-throughput screening using liquid handling robotics.


Our cell-free toolkits spans model organisms like E. coli to non-model species including Streptomyces venezuelae and Klebsiella pneumoniae, enabling rapid prototyping of biosynthetic pathways and gene expression regulation, without the constraints of living cells. We have established automated platforms for scalable biosynthesis and developed a dedicated Streptomyces cell-free toolkit for natural product discovery.

 

Selected Publications:
  • Andrew J. Rice, Tien T. Sword, Kameshwari Chengan, Douglas A. Mitchell, Nigel J. Mouncey, Simon J. Moore and Constance B. Bailey. Cell-free synthetic biology for natural product biosynthesis and discovery. Chemical Society Reviews (2025) 54:4314-4352
  • Kameshwari Chengan, Charlotte Hind, Maria Stanley, Matthew E Wand, Lakshmeesha K Nagappa, Kevin Howland, Tanith Hanson, Rubén Martín-Escolano, Anastasios D Tsaousis, José A Bengoechea, J Mark Sutton, Christopher M Smales, Simon J Moore. A cell-free strategy for the host-specific profiling of antimicrobial sensitivity and resistance. npj Antimicrobials and Resistance 1:16 (2023)
  • Lakshmeesha K. Nagappa, Wakana Sato, Farzana Alam, Kameshwari Chengan, Christopher M. Smales, Tobias Von Der Haar, Karen M. Polizzi, Katarzyna P. Adamala and Simon J. Moore. A ubiquitous amino acid source for prokaryotic and eukaryotic cell-free transcription-translation systems. Front. Bioeng. Biotechnol. (2022) 10:992708

 

Antimicrobial Discovery & Resistance Mechanisms

Antimicrobial resistance is a global challenge which we address through an innovative platform: cell-free protein synthesis as a rapid tool for studying antimicrobial sensitivity and resistance mechanisms.

Our BBSRC-funded collaboration with the UK Health Security Agency (UKHSA) focuses on developing alternative antimicrobials and understanding resistance evolution in ESKAPE pathogens, such as Klebsiella pneumoniae and Acinetobacter baumannii. Our cell-free platform enables rapid testing of antimicrobial peptides and proteins, including engineered variants, without the constraints of living cells, allowing quick assessment of new compounds and understanding of resistance mechanism evolution.

 

Selected Publications:
  • Kameshwari Chengan, Charlotte Hind, Maria Stanley, Matthew E Wand, Lakshmeesha K Nagappa, Kevin Howland, Tanith Hanson, Rubén Martín-Escolano, Anastasios D Tsaousis, José A Bengoechea, J Mark Sutton, Christopher M Smales, Simon J Moore. A cell-free strategy for the host-specific profiling of antimicrobial sensitivity and resistance. npj Antimicrobials and Resistance 1:16 (2023)
  • Andrew J. Rice, Tien T. Sword, Kameshwari Chengan, Douglas A. Mitchell, Nigel J. Mouncey, Simon J. Moore and Constance B. Bailey. Cell-free synthetic biology for natural product biosynthesis and discovery. Chemical Society Reviews (2025) 54:4314-4352
  • Sebastián Bermúdez-Puga, Meriellen Dias, Iara Lima Reis, Taciana Freire de Oliveira, Sonia Regina Yokomizo de Almeida, Maria Anita Mendes, Simon J Moore, José R Almeida, Carolina Proano-Bolanos, Ricardo Pinheiro de Souza Oliveira. Microscopic and metabolomics analysis of the anti-Listeria activity of natural and engineered cruzioseptins. Biochimie (2024) 225:168-175

GRANTS

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  • GRANT
    Wellcome Trust SEED award
    Wellcome Trust1 Jun 2025 - 31 May 2021
  • GRANT
    A Cell-Free Toolbox to Anticipate, Learn and Counter Antimicrobial Resistance
    Biotechnology and Biological Sciences Research Council1 May 2024 - 30 Apr 2027
  • GRANT
    iCASE studentship
    Industry - Syngenta30 Sep 2023 - 29 Sep 2027
  • GRANT
    Royal Society Equipment Grant
    Royal Society1 Mar 2023 - 29 Feb 2024
  • GRANT
    Feasibility study
    Future Targeted Manufacturing Healthcare hub (EPSRC)1 Sep 2022 - 31 May 2023
  • GRANT
    Eric Reid Fund for Methodology
    Biochemical Society1 May 2022 - 1 Jun 2022
  • GRANT
    How do bacteria translate megasynthases for natural product biosynthesis?
    Leverhulme Trust1 Sep 2021 - 31 Aug 2024
  • GRANT
    Business Interaction Voucher
    High-Value Biorenewables Network (BBSRC)1 Sep 2020 - 31 Dec 2020
  • GRANT
    Royal Society Equipment Grant
    Royal Society1 Mar 2019 - 29 Feb 2020
  • FELLOWSHIP
    Wellcome Trust ISSF Fellowship
    Wellcome Trust