Publications

Oxytetracycline hyper-production through targeted genome reduction of Streptomyces rimosus

Pšeničnik Alen, Slemc Lucija, Avbelj Martina, Tome Miha, Šala Martin, Herron Paul, Shmatkov Maksym, Petek Marko, Baebler Špela, Mrak Peter, Hranueli Daslav, Starčević Antonio, Hunter Iain S, Petković Hrvoje

mSystems Vol 9 (2024)

https://doi.org/10.1128/msystems.00250-24

Streptomyces salinarius sp. nov., an actinomycete isolated from solar saltern soil

Klanbut Khanungkan, Rattanakavil Thitiya, Duangupama Thitikorn, Suriyachadkun Chanwit, Herron Paul Robert, Thawai Chitti

International Journal of Systematic and Evolutionary Microbiology Vol 73 (2023)

https://doi.org/10.1099/ijsem.0.005863

Phosphoproteome dynamics of streptomyces rimosus during submerged growth and antibiotic production

Šarić Ela, Quinn Gerry A, Nalpas Nicolas, Paradžik Tina, Kazazić Saša, Filić Želimira, Šemanjski Maja, Herron Paul, Hunter Iain, Maček Boris, Vujaklija Dušica

mSystems Vol 7 (2022)

https://doi.org/10.1128/msystems.00199-22

Bilateral symmetry of linear streptomycete chromosomes

Algora-Gallardo Lis, Schniete Jana K, Mark David R, Hunter Iain S, Herron Paul R

Microbial Genomics Vol 7 (2021)

https://doi.org/10.1099/mgen.0.000692

Genome editing reveals that pSCL4 is required for chromosome linearity in Streptomyces clavuligerus

Gomez-Escribano Juan Pablo, Algora Gallardo Lis, Bozhüyük Kenan A J, Kendrew Steven G, Huckle Benjamin D, Crowhurst Nicola A, Bibb Mervyn J, Collis Andrew J, Micklefield Jason, Herron Paul R, Wilkinson Barrie

Microbial Genomics Vol 7 (2021)

https://doi.org/10.1099/mgen.0.000669

Adaptation to endophytic lifestyle through genome reduction by Kitasatospora sp. SUK42

Zin Noraziah M, Ismail Aisha, Mark David R, Westrop Gareth, Schniete Jana K, Herron Paul

Frontiers in Bioengineering and Biotechnology Vol 9 (2021)

https://doi.org/10.3389/fbioe.2021.740722

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Teaching

My teaching duties include Fundamental Microbiology, Intermediate Microbiology, Laboratory Methods and Skills Development, Honours Microbiology 1 and 2.

Research Interests

His research interests include the following:

• Chromosome segregation in Streptomyces. cell division in streptomycetes is fundamentally different from other bacteria as it is inessential for growth. Despite progress on elucidating the regulatory mechanisms governing the onset of differentiation in streptomycetes, little is known about the mechanism of chromosome segregation. We are using molecular and microscopic tools to investigate this in Streptomyces. Using time lapse microscopy we have visualised trafficking of key cell division proteins and DNA replisomesduring growth and development.The role of Phospholipids in streptomycete development. The involvement of phospholipids in bacterial cell division has recently received increasing attention. Although different phospholipids are abundant in the membranes of Streptomyces, their involvement in development is not known. We are investigating changes in phospholipid profile and gene expression during differentiation.
• Oxytetracycline productivity in Streptomyces rimosus. In the commercial production of antibiotics, extensive strain improvement programs have been carried out, where the original isolate of an antibiotic-producing organism has been improved sequentially to deliver a titre of product that is commercially-viable. This "black box" methodology was carried out for Streptomyces rimosus, which makes the antibiotic oxytetracycline. To identify the basis of strain improvement we have sequenced the genomes of four S. rimosus strains and are attempting to understand the genetic changes and biochemical bottlenecks by which carbon flux is directed away from primary metabolism towards natural product biosynthesis.
• Exploitaion of Bacteriophages. In collaboration Fixed Phage Ltd. we are exploiting bacterial viruses for the treatment of plant and animal diseases

Professional Activities

PhD Examiner

External Examiner

11/4/2016

Microbiology (Journal)

Peer reviewer

5/4/2016

Metabolomics (Journal)

Peer reviewer

8/2/2016

Gene (Journal)

Peer reviewer

29/1/2016

Open Biology (Journal)

Peer reviewer

25/1/2016

Nature Communications (Journal)

Peer reviewer

19/1/2016

More professional activities

Projects

Linking Genotype to Phenotype for Faster Antibiotic Discovery - 2. Vertically Integrated Projects for Sustainable Development (VIP4SD) Lady Curran Summer Internship (2021)

Feeney, Morgan (Principal Investigator) Herron, Paul (Co-investigator) Murray, Paul (Co-investigator)

21-Jun-2021 - 18-Aug-2021

Development of stable platform strains for improved clavulanic acid production

Herron, Paul (Principal Investigator)

01-Oct-2019 - 30-Sep-2023

Research Excellence Award - Applying machine learning to 'omics data for accelerated marine antibiotic discovery - Darren Scobie

Duncan, Katherine (Principal Investigator) Herron, Paul (Co-investigator)

01-Oct-2019 - 30-Sep-2022

Development of novel bacterial strains for production of hydrophobic compounds (CBMNet PoC)

Herron, Paul (Principal Investigator)

01-Feb-2018 - 20-Feb-2019

Development of Stable Streptomyces clavuligeris strains for improved clavalunic acid production

Herron, Paul (Principal Investigator) Hoskisson, Paul (Co-investigator)

01-Oct-2016 - 31-Mar-2020

A universal tool for rapid functional characterisation of antibiotic production genes in bacterial genus,Streptomyces

Herron, Paul (Principal Investigator)

During this project we will develop a genetic tool that will accelerate and simplify the discovery of new antibiotics produced by the bacterial genus Streptomyces. Ever since the golden age of antibiotics in the mid-20th century, streptomycetes have provided the richest source of novel antimicrobial compounds. These natural products include clinically-important antibiotics (tetracyclines, streptomycins, & penicillins), immunosuppressants (FK506/520 & rapamycin) and anti-cancer drugs (doxorubicin). Perhaps the major medical challenge in the 21st century is to develop new antibiotics to combat bacterial antibiotic resistance. Genome sequencing of streptomycetes, coupled with mining for antibiotic biosynthetic genes has revealed great undiscovered biosynthetic potential in this genus and highlights their enormous possibilities for antibiotic development. However, there is a need to develop new genetic tools that will allow the rapid characterization of antibiotic biosynthetic gene function and facilitate exploitation of this biochemical potential. Currently, gene disruption in streptomycetes is a laborious process. We need to speed this process to more rapidly characterise antibiotic biosynthetic genes and so simplify the antibiotic development pipeline. Rapid mutagenesis of biosynthetic genes will allow manipulation of pathways to develop new compounds through genetic engineering. Alternatively gene manipulation of a producing-strain can be used to improve yield and thus commercial viability of desired antibiotics. Taking advantage of gene synthesis technology, we will develop a genetic tool that is universally applicable to all sequenced streptomycetes as well as some related bacteria. This tool will remove the need for laborious gene manipulations that is necessary to characterise antibiotic biosynthesis at the present time. In the first instance, we will synthesise mutagenesis cassettes targeted at the disruption of a number of characterised antibiotic biosynthetic gene clusters. We will demonstrate proof-of-principle of this system in both a model streptomycete, Streptomyces coelicolor, and an industrial strain, the oxytetracycline producer Streptomyces rimosus through the disruption and deletion of known antibiotic biosynthetic genes. Application of our tool to the latter organism will demonstrate the utility of our system in non-model, industrial organisms. We will assess the efficiency with which gene disruption takes place and identify the location and stability of the gene disruption using a range of molecular biological techniques. Finally, we will make the genetic tools developed during this project available to the academic and industrial scientific communities through a biological resource repository following dissemination of results in open access journals so as to achieve the greatest possible uptake of our system for the development of novel antibiotics.

01-Oct-2015 - 16-Jan-2018

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