Dr Leanne Pearson-Neilan

Dr Leanne Pearson-Neilan

Senior Research Associate

School of Environmental and Life Sciences

Career Summary

Biography

Leanne is a researcher and science writer specialising in environmental microbiology, water quality and natural products research. After completing her PhD at the University of NSW in 2007 on the biosynthesis of microcystin tailoring and transport enzymes in toxic cyanobacteria ('blue-green algae'), she expanded her research to include a variety of other environmental biotoxins and natural products. She is particularly interested in 'how' and 'why' these 'specialised metabolites' are produced, as well as their impacts on human health and the environment.

Since relocating to the University of Newcastle in 2017, her research has shifted focus to the exploitation of so-called environmental 'toxins' as industrially and pharmaceutically valuable products. Because many natural product producers are difficult to culture and manipulate in the lab, a synthetic biology approach is often necessary to unlock their biochemical potential. This emerging field involves mining microbial genomes for biosynthesis gene clusters (BGCs), characterising the pathways encoded therein, and manipulating and overexpressing these pathways in a heterologous organism, such as E. coli.

Leanne is a member of the Neilan Lab of Microbial and Molecular Diversity within the School of Environmental and Life Sciences.


Qualifications

  • Doctor of Philosophy, University of New South Wales

Keywords

  • biotoxins
  • cyanobacteria
  • editing
  • microbiology
  • molecular biology
  • scientific writing
  • synthetic biology

Languages

  • English (Mother)

Fields of Research

Code Description Percentage
310113 Synthetic biology 25
310703 Microbial ecology 25
310704 Microbial genetics 50

Professional Experience

UON Appointment

Title Organisation / Department
Senior Research Associate University of Newcastle
School of Environmental and Life Sciences
Australia

Academic appointment

Dates Title Organisation / Department
1/1/2008 - 31/12/2016 Postdoctoral Research Associate The University of New South Wales
Biotechnology and Biomolecular Sciences
Australia
Edit

Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Chapter (6 outputs)

Year Citation Altmetrics Link
2021 Pearson-Neilan L, Neilan BA, 'Protozoan Diversity and Biogeography', Encyclopedia of Life Sciences, Wiley, Hoboken, New Jersey (2021)
Co-authors Brett Neilan
2018 Pearson LA, Neilan BA, 'Saxitoxin and Related Paralytic Shellfish Toxins', Handbook of Foodborne Diseases, CRC Press, Boca Raton, FL (2018)
Co-authors Brett Neilan
2014 Pearson LA, Neilan BA, 'Saxitoxin and Related Paralytic Shellfish Poisons', Manual of Security Sensitive Microbes and Toxins, CRC Press, Boca Raton, FL 511-518 (2014)
Co-authors Brett Neilan
2013 Rai AK, Pearson LA, Kumar A, 'Hepatotoxic microcystins of cyanobacteria: Biosynthesis and degradation in response to abiotic stress', Stress Biology of Cyanobacteria: Molecular Mechanisms to Cellular Responses 341-350 (2013)

Cyanobacteria (blue-green algae) are an ancient group of microorganisms that thrive in a broad spectrum of terrestrial, freshwater, and marine habitats ranging from hot springs to... [more]

Cyanobacteria (blue-green algae) are an ancient group of microorganisms that thrive in a broad spectrum of terrestrial, freshwater, and marine habitats ranging from hot springs to frozen ponds [1]. The successful colonization of this wide range of environments by cyanobacteria is linked to their long evolutionary history and adaptation to a number of environmental stresses such as high solar UV radiation, extreme temperatures, desiccation, oxidative stress, and nutrient fluctuations. Present-day cyanobacteria perform oxygenic photosynthesis and possess chlorophyll a and water-soluble phycobilin proteins [2,3]. Additionally, certain members of this order are capable of fixing atmospheric dinitrogen gas (N2), allowing them to colonize environments lacking a stable supply of fixed nitrogen [2]. A range of environmental conditions including higher temperatures and pH values, low turbulence, and high nutrient levels (eutrophication) can result in the proliferation of planktonic cyanobacteria in lakes and reservoirs, often leading to the formation of huge surface blooms. Certain bloom-forming cyanobacteria are also capable of producing secondary metabolites, which have a range of bioactivities, some of which are highly toxic to eukaryotic organisms including humans. Cyanotoxins are very diverse in terms of their chemical structure as well as their toxicity [4-7]. Based on the toxic effects they elicit, they may be classified as dermatotoxins (lipopolysaccharides, lyngbyatoxin-a, and aplysiatoxins), neurotoxins (anatoxin-a, homoanatoxin-a, anatoxin-a(s), and saxitoxins), and hepatotoxins (microcystins, nodularin, and cylindrospermopsin) [8-11]. Generally, these toxins are present within cells but can be released in high concentrations during cell lysis [10] or via active transport mechanisms [12].

DOI 10.1201/b13853
Citations Scopus - 2
2009 Pearson L, Neilan B, 'Nonribosomal peptides', Bioactive Peptides, Taylor and Francis, Florida, USA 277-312 (2009)
Co-authors Brett Neilan
2008 Pearson L, Neilan BA, Moffitt MC, Kaebernick M, Kellmann R, Pomati F, 'The genetics and genomics of cyanobacterial toxicity', Cyanobacterial Harmful Algal Blooms: State of the Science and Research Needs, Springer Science & Business Media, New York (2008)
Co-authors Brett Neilan
Show 3 more chapters

Journal article (27 outputs)

Year Citation Altmetrics Link
2021 Ingrey SD, Pearson LA, Kalaitzis JA, Neilan BA, 'Australian bush medicines harbour diverse microbial endophytes with broad-spectrum antibacterial activity.', J Appl Microbiol, (2021)
DOI 10.1111/jam.15122
Co-authors Brett Neilan
2021 Chau R, Pearson LA, Cain J, Kalaitzis JA, Neilan BA, 'A Pseudoalteromonas Clade with Remarkable Biosynthetic Potential', Applied and Environmental Microbiology, 87 1-16 (2021) [C1]

Pseudoalteromonas species produce a diverse range of biologically active compounds, including those biosynthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synth... [more]

Pseudoalteromonas species produce a diverse range of biologically active compounds, including those biosynthesized by nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs). Here, we report the biochemical and genomic analysis of Pseudoalteromonas sp. strain HM-SA03, isolated from the blue-ringed octopus, Hapalochlaena sp. Genome mining for secondary metabolite pathways revealed seven putative NRPS/PKS biosynthesis gene clusters, including those for the biosynthesis of alterochromides, pseudoalterobactins, alteramides, and four novel compounds. Among these was a novel siderophore biosynthesis gene cluster with unprecedented architecture (NRPS-PKS-NRPS-PKS-NRPS-PKS-NRPS). Alterochromide production in HM-SA03 was also confirmed by liquid chromatography-mass spectrometry. An investigation of the biosynthetic potential of 42 publicly available Pseudoalteromonas genomes indicated that some of these gene clusters are distributed throughout the genus. Through the phylogenetic analysis, a particular subset of strains formed a clade with extraordinary biosynthetic potential, with an average density of 10 biosynthesis gene clusters per genome. In contrast, the majority of Pseudoalteromonas strains outside this clade contained an average of three clusters encoding complex biosynthesis. These results highlight the underexplored potential of Pseudoalteromonas as a source of new natural products. Importance This study demonstrates that the Pseudoalteromonas strain HM-SA03, isolated from the venomous blue-ringed octopus, Hapalochalaena sp., is a biosynthetically talented organism, capable of producing alterochromides and potentially six other specialized metabolites. We identified a pseudoalterobactin biosynthesis gene cluster and proposed a pathway for the production of the associated siderophore. A novel siderophore biosynthesis gene cluster with unprecedented architecture was also identified in the HM-SA03 genome. Finally, we demonstrated that HM-SA03 belongs to a phylogenetic clade of strains with extraordinary biosynthetic potential. While our results do not support a role of HM-SA03 in Hapalochalaena sp. venom (tetrodotoxin) production, they emphasize the untapped potential of Pseudoalteromonas as a source of novel natural products.

DOI 10.1128/AEM.02604-20
Citations Scopus - 1Web of Science - 1
Co-authors Brett Neilan
2021 Romanis CS, Pearson LA, Neilan BA, 'Cyanobacterial blooms in wastewater treatment facilities: Significance and emerging monitoring strategies', JOURNAL OF MICROBIOLOGICAL METHODS, 180 (2021) [C1]
DOI 10.1016/j.mimet.2020.106123
Citations Scopus - 2Web of Science - 1
Co-authors Brett Neilan
2021 Soeriyadi AH, Mazmouz R, Pickford R, Al-Sinawi B, Kellmann R, Pearson LA, Neilan BA, 'Cover Feature: Heterologous Expression of an Unusual Ketosynthase, SxtA, Leads to Production of Saxitoxin Intermediates in Escherichia coli (5/2021)', ChemBioChem, 22 762-762 (2021)
DOI 10.1002/cbic.202100062
Co-authors Brett Neilan
2021 Pearson LA, D'Agostino PM, Neilan BA, 'Recent developments in quantitative PCR for monitoring harmful marine microalgae', Harmful Algae, 108 (2021)

Marine microalgae produce a variety of specialised metabolites that have toxic effects on humans, farmed fish, and marine wildlife. Alarmingly, many of these compounds bioaccumula... [more]

Marine microalgae produce a variety of specialised metabolites that have toxic effects on humans, farmed fish, and marine wildlife. Alarmingly, many of these compounds bioaccumulate in the tissues of shellfish and higher trophic organisms, including species consumed by humans. Molecular methods are emerging as a potential alternative and complement to the conventional microscopic diagnosis of toxic or otherwise harmful microalgal species. Quantitative PCR (qPCR) in particular, has gained popularity over the past decade as a sensitive, rapid, and cost-effective method for monitoring harmful microalgae. Assays targeting taxonomic marker genes provide the opportunity to identify and quantify (or semi-quantify) microalgal species and importantly to pre-empt bloom events. Moreover, the discovery of paralytic shellfish toxin biosynthesis genes in dinoflagellates has enabled researchers to directly monitor toxigenic species in coastal waters and fisheries. This review summarises the recent developments in qPCR detection methods for harmful microalgae, with emphasis on emerging toxin gene monitoring technologies.

DOI 10.1016/j.hal.2021.102096
Co-authors Brett Neilan
2021 Larsen JS, Pearson LA, Neilan BA, 'Genome Mining and Evolutionary Analysis Reveal Diverse Type III Polyketide Synthase Pathways in Cyanobacteria.', Genome biology and evolution, 13 (2021) [C1]
DOI 10.1093/gbe/evab056
Citations Web of Science - 1
Co-authors Brett Neilan
2020 Pearson LA, Crosbie ND, Neilan BA, 'Distribution and conservation of known secondary metabolite biosynthesis gene clusters in the genomes of geographically diverse Microcystis aeruginosa strains', Marine and Freshwater Research, 71 701-716 (2020) [C1]
DOI 10.1071/MF18406
Citations Scopus - 6Web of Science - 6
Co-authors Brett Neilan
2020 Soeriyadi AH, Mazmouz R, Pickford R, Al-Sinawi B, Kellmann R, Pearson LA, Neilan BA, 'Heterologous Expression of an Unusual Ketosynthase, SxtA, Leads to Production of Saxitoxin Intermediates in Escherichia coli', CHEMBIOCHEM, 22 845-849 (2020) [C1]
DOI 10.1002/cbic.202000675
Citations Scopus - 1Web of Science - 1
Co-authors Brett Neilan
2019 Liu T, Mazmouz R, Pearson LA, Neilan BA, 'Mutagenesis of the Microcystin Tailoring and Transport Proteins in a Heterologous Cyanotoxin Expression System', ACS Synthetic Biology, 8 1187-1194 (2019) [C1]
DOI 10.1021/acssynbio.9b00068
Citations Scopus - 4Web of Science - 4
Co-authors Brett Neilan
2019 Cullen A, Pearson LA, Mazmouz R, Liu T, Soeriyadi AH, Ongley SE, Neilan BA, 'Heterologous expression and biochemical characterisation of cyanotoxin biosynthesis pathways', NATURAL PRODUCT REPORTS, 36 1117-1136 (2019) [C1]
DOI 10.1039/c8np00063h
Citations Scopus - 8Web of Science - 8
Co-authors Brett Neilan
2016 Katoch M, Mazmouz R, Chau R, Pearson LA, Pickford R, Neilan BA, 'Heterologous production of cyanobacterial mycosporine-like amino acids mycosporine-ornithine and mycosporine-lysine in Escherichia coli', Applied and Environmental Microbiology, 82 6167-6173 (2016) [C1]
DOI 10.1128/AEM.01632-16
Citations Scopus - 31Web of Science - 27
Co-authors Brett Neilan
2016 Pearson LA, Dittmann E, Mazmouz R, Ongley SE, D'Agostino PM, Neilan BA, 'The genetics, biosynthesis and regulation of toxic specialized metabolites of cyanobacteria', Harmful Algae, 54 98-111 (2016) [C1]
DOI 10.1016/j.hal.2015.11.002
Citations Scopus - 56Web of Science - 56
Co-authors Brett Neilan
2015 Hudek L, Pearson L, Michalczyk AA, Bräu L, Neilan BA, Ackland ML, 'Characterization of two cation diffusion facilitators NpunF0707 and NpunF1794 in Nostoc punctiforme', Journal of Applied Microbiology, 119 1357-1370 (2015) [C1]

Aims: To characterize genes involved in maintaining homeostatic levels of zinc in the cyanobacterium Nostoc punctiforme. Methods and Results: Metal efflux transporters play a cent... [more]

Aims: To characterize genes involved in maintaining homeostatic levels of zinc in the cyanobacterium Nostoc punctiforme. Methods and Results: Metal efflux transporters play a central role in maintaining homeostatic levels of trace elements such as zinc. Sequence analyses of the N. punctiforme genome identified two potential cation diffusion facilitator (CDF) metal efflux transporters, Npun_F0707 (Cdf31) and Npun_F1794 (Cdf33). Deletion of either Cdf31or Cdf33 resulted in increased zinc retention over 3 h. Interestingly, Cdf31- and Cdf33- mutants showed no change in sensitivity to zinc exposure in comparison with the wild type, suggesting some compensatory capacity for the loss of each other. Using qRT-PCR, a possible interaction was observed between the two cdf's, where the Cdf31- mutant had a more profound effect on cdf33 expression than Cdf33- did on cdf31. Over-expression of Cdf31 and Cdf33 in ZntA-- and ZitB--deficient Escherichia coli revealed function similarities between the ZntA and ZitB of E. coli and the cyanobacterial transporters. Conclusions: The data presented shed light on the function of two important transporters that regulate zinc homeostasis in N. punctiforme. Significance and Impact of the Study: This study shows for the first time the functional characterization of two cyanobacterial zinc efflux proteins belonging to the CDF family.

DOI 10.1111/jam.12942
Citations Scopus - 3Web of Science - 1
Co-authors Brett Neilan
2014 Sinha R, Pearson LA, Davis TW, Muenchhoff J, Pratama R, Jex A, et al., 'Comparative genomics of Cylindrospermopsis raciborskii strains with differential toxicities', BMC GENOMICS, 15 (2014) [C1]
DOI 10.1186/1471-2164-15-83
Citations Scopus - 45Web of Science - 41
Co-authors Brett Neilan
2013 Neilan BA, Pearson LA, Muenchhoff J, Moffitt MC, Dittmann E, 'Environmental conditions that influence toxin biosynthesis in cyanobacteria', ENVIRONMENTAL MICROBIOLOGY, 15 1239-1253 (2013) [C1]
DOI 10.1111/j.1462-2920.2012.02729.x
Citations Scopus - 209Web of Science - 193
Co-authors Brett Neilan
2013 Hudek L, Pearson LA, Michalczyk A, Neilan BA, Ackland ML, 'Molecular and cellular characterisation of the zinc uptake (Znu) system of nostoc punctiforme', FEMS Microbiology Ecology, 86 149-171 (2013) [C1]

Metal homoeostasis in cyanobacteria is based on uptake and export systems that are controlled by their own regulators. This study characterises the zinc uptake (Znu) system in Nos... [more]

Metal homoeostasis in cyanobacteria is based on uptake and export systems that are controlled by their own regulators. This study characterises the zinc uptake (Znu) system in Nostoc punctiforme. The system was found to comprise of three subunits in an ACB operon: a Zn2+-binding protein (ZnuA18), a transmembrane domain (ZnuB) and an ATPase (ZnuC). These proteins are encoded within the znu operon regulated by a zinc uptake transcription repressor (Zur). Interestingly, a second Zn2+-binding protein (ZnuA08) was also identified at a distal genomic location. Interactions between components of the ZnuACB system were investigated using knockouts of the individual genes. The znuA08-, znuA18-, znuB- and znuC- mutants displayed overall reduced znuACB transcript levels, suggesting that all system components are required for normal expression of znu genes. Zinc uptake assays in the Zn2+-binding protein mutant strains showed that the disruption of znuA18 had a greater negative effect on zinc uptake than disruption of znuA08. Complementation studies in Escherichia coli indicated that both znuA08 and znuA18 were able to restore zinc uptake in a znuA- mutant, with znuA18 permitting the highest zinc uptake rate. The N. punctiforme zur was also able to complement the E. coli zur- mutant. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

DOI 10.1111/1574-6941.12153
Citations Scopus - 11Web of Science - 8
Co-authors Brett Neilan
2013 Hudek L, Pearson LA, Michalczyk A, Neilan BA, Ackland ML, 'Functional characterization of the twin ZIP/SLC39 metal transporters, NpunF3111 and NpunF2202 in Nostoc punctiforme', Applied Microbiology and Biotechnology, 97 8649-8662 (2013) [C1]

The ZIP family of metal transporters is involved in the transport of Zn2+ and other metal cations from the extracellular environment and/or organelles into the cytoplasm of prokar... [more]

The ZIP family of metal transporters is involved in the transport of Zn2+ and other metal cations from the extracellular environment and/or organelles into the cytoplasm of prokaryotes, eukaryotes and archaeotes. In the present study, we identified twin ZIP transporters, Zip11 (Npun-F3111) and Zip63 (Npun-F2202) encoded within the genome of the filamentous cyanobacterium, Nostoc punctiforme PCC73120. Sequence-based analyses and structural predictions confirmed that these cyanobacterial transporters belong to the SLC39 subfamily of metal transporters. Quantitative real-time (QRT)-PCR analyses suggested that the enzymes encoded by zip11 and zip63 have a broad allocrite range that includes zinc as well as cadmium, cobalt, copper, manganese and nickel. Inactivation of either zip11 or zip63 via insertional mutagenesis in N. punctiforme resulted in reduced expression of both genes, highlighting a possible co-regulation mechanism. Uptake experiments using 65Zn demonstrated that both zip mutants had diminished zinc uptake capacity, with the deletion of zip11 resulting in the greatest overall reduction in 65Zn uptake. Over-expression of Zip11 and Zip63 in an E. coli mutant strain (ZupT736::kan) restored divalent metal cation uptake, providing further evidence that these transporters are involved in Zn uptake in N. punctiforme. Our findings show the functional role of these twin metal uptake transporters in N. punctiforme, which are independently expressed in the presence of an array of metals. Both Zip11 and Zip63 are required for the maintenance of homeostatic levels of intracellular zinc N. punctiforme, although Zip11 appears to be the primary zinc transporter in this cyanobacterium, both ZIP's may be part of a larger metal uptake system with shared regulatory elements. © 2013 Springer-Verlag Berlin Heidelberg.

DOI 10.1007/s00253-013-5047-y
Citations Scopus - 11Web of Science - 8
Co-authors Brett Neilan
2012 Sinha R, Pearson LA, Davis TW, Burford MA, Orr PT, Neilan BA, 'Increased incidence of Cylindrospermopsis raciborskii in temperate zones - Is climate change responsible?', Water Research, 46 1408-1419 (2012) [C1]

The bloom-forming, toxic cyanobacterium, Cylindrospermopsis raciborskii exhibits global distribution. In recent years both the occurrence and dominance of this species, particular... [more]

The bloom-forming, toxic cyanobacterium, Cylindrospermopsis raciborskii exhibits global distribution. In recent years both the occurrence and dominance of this species, particularly in temperate regions, has increased. Whilst this may be due to increased sensitivity of analytical detection methods or more rigorous sampling routines, it is possible that this expansion has been assisted by a number of changing conditions in these environments. The geographical expansion of both the organism and toxin production can be attributed to phenomena such as eutrophication and climate change. In this review, we discuss the occurrence of C. raciborskii with respect to current literature against the backdrop of increasing global temperatures. Critically, we identify a concerning trend between the geographical spread of this organism and global climate change. © 2011.

DOI 10.1016/j.watres.2011.12.019
Citations Scopus - 135Web of Science - 127
Co-authors Brett Neilan
2012 Al-Tebrineh J, Pearson LA, Yasar SA, Neilan BA, 'A multiplex qPCR targeting hepato- and neurotoxigenic cyanobacteria of global significance', Harmful Algae, 15 19-25 (2012) [C1]

Toxic bloom-forming cyanobacteria are a global health hazard. These photosynthetic microorganisms produce a suite of secondary metabolite toxins including hepatotoxins such as mic... [more]

Toxic bloom-forming cyanobacteria are a global health hazard. These photosynthetic microorganisms produce a suite of secondary metabolite toxins including hepatotoxins such as microcystin, nodularin and cylindrospermopsin and neurotoxins such as saxitoxin. These toxins can threaten the safety of drinking water supplies and in the case of saxitoxin, can accumulate to dangerous levels in shellfish, affecting the seafood industry. Several molecular methods have been described for the detection and quantification of toxigenic cyanobacteria, however, to date there is no method for the simultaneous detection and quantification of hepatotoxin and neurotoxin producing genera. This paper describes the development and validation of a quadruplex quantitative-PCR (qPCR) assay capable of detecting and quantifying toxin genes from the microcystin, nodularin, cylindrospermopsin and saxitoxin biosynthesis pathways. The primers and probes employed in this assay were designed from conserved regions within toxin biosynthesis genes from most of the representative cyanobacterial genera. The qPCR assay was optimized to reliably determine the copy number of cyanotoxin biosynthesis genes, as well as an internal cyanobacteria 16S rDNA control, in a single reaction. Amplification efficiency and reproducibility were similar among the cyanotoxin genes, while the sensitivity of the reaction for the toxin genes ranged from 10 2 to 10 6 gene copies per reaction. This multiplex qPCR assay is a powerful tool for detecting and quantifying potentially toxic cyanobacteria in laboratory and field samples. Such technology will enable water quality and food safety authorities to better forecast, evaluate and reduce the impact of future harmful algal bloom events. © 2011.

DOI 10.1016/j.hal.2011.11.001
Citations Scopus - 46Web of Science - 48
Co-authors Brett Neilan
2010 Ginn HP, Pearson LA, Neilan BA, 'NtcA from microcystis aeruginosa PCC 7806 is autoregulatory and binds to the microcystin promoter', Applied and Environmental Microbiology, 76 4362-4368 (2010)

NtcA is a transcription factor that has been found in a diverse range of cyanobacteria. This nitrogencontrolled factor was focused on as a key component in the yet-to-be-deciphere... [more]

NtcA is a transcription factor that has been found in a diverse range of cyanobacteria. This nitrogencontrolled factor was focused on as a key component in the yet-to-be-deciphered regulatory network controlling microcystin production. Adaptor-mediated PCR was utilized to isolate the ntcA gene from Microcystis aeruginosa PCC 7806. This gene was cloned, and the recombinant (His-tagged) protein was overexpressed and purified for use in mobility shift assays to analyze NtcA binding to putative sites identified in the microcystin mcyA/D promoter region. Autoregulation of NtcA in M. aeruginosa was shown via NtcA binding in the upstream ntcA promoter region. The observation of binding of NtcA to the mcyA/D promoter region has direct relevance for the regulation of microcystin biosynthesis, as transcription of the mcyABCDEFGHIJ gene cluster appears to be under direct control of nitrogen. Copyright © 2010, American Microbiology, All Rights Reserved.

DOI 10.1128/AEM.01862-09
Citations Scopus - 61Web of Science - 59
Co-authors Brett Neilan
2010 Pearson L, Mihali T, Moffitt M, Kellmann R, Neilan B, 'On the chemistry, toxicology and genetics of the cyanobacterial toxins, microcystin, nodularin, saxitoxin and cylindrospermopsin', Marine Drugs, 8 1650-1680 (2010)

The cyanobacteria or "blue-green algae", as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic a... [more]

The cyanobacteria or "blue-green algae", as they are commonly termed, comprise a diverse group of oxygenic photosynthetic bacteria that inhabit a wide range of aquatic and terrestrial environments, and display incredible morphological diversity. Many aquatic, bloom-forming species of cyanobacteria are capable of producing biologically active secondary metabolites, which are highly toxic to humans and other animals. From a toxicological viewpoint, the cyanotoxins span four major classes: the neurotoxins, hepatotoxins, cytotoxins, and dermatoxins (irritant toxins). However, structurally they are quite diverse. Over the past decade, the biosynthesis pathways of the four major cyanotoxins: microcystin, nodularin, saxitoxin and cylindrospermopsin, have been genetically and biochemically elucidated. This review provides an overview of these biosynthesis pathways and additionally summarizes the chemistry and toxicology of these remarkable secondary metabolites. © 2010 by the authors; licensee MDPI.

DOI 10.3390/md8051650
Citations Scopus - 369Web of Science - 356
Co-authors Brett Neilan
2009 Ginn HP, Pearson LA, Neilan BA, 'Hepatotoxin biosynthesis and regulation in cyanobacteria- The putative involvement of nitrogen and iron homeostasis mechanisms', Chiang Mai Journal of Science, 36 200-223 (2009)

Cyanobacteria are recognised globally as a human health threat due to their proliferation into toxic blooms. Of particular concern are strains that produce the hepatotoxins, micro... [more]

Cyanobacteria are recognised globally as a human health threat due to their proliferation into toxic blooms. Of particular concern are strains that produce the hepatotoxins, microcystin and nodularin. Research over the past decade has revealed the biochemical and molecular mechanisms behind hepatotoxin production. However, there is still much to learn regarding the regulation of these biologically active metabolites. This review provides an overview of cyanobacterial hepatotoxin research to date and additionally, elaborates on the putative involvement of nitrogen and iron homeostatic mechanisms in cyanotoxin regulation.

Citations Scopus - 7Web of Science - 7
Co-authors Brett Neilan
2008 Neilan BA, Pearson LA, Moffitt MC, Mihali KT, Kaebernick M, Kellmann R, Pomati F, 'The genetics and genomics of cyanobacterial toxicity.', Advances in experimental medicine and biology, 619 417-452 (2008)
DOI 10.1007/978-0-387-75865-7_17
Citations Scopus - 27
Co-authors Brett Neilan
2008 Pearson LA, Neilan BA, 'The molecular genetics of cyanobacterial toxicity as a basis for monitoring water quality and public health risk', Current Opinion in Biotechnology, 19 281-288 (2008)

Toxic cyanobacteria pose a significant hazard to human health and the environment. The recent characterisation of cyanotoxin synthetase gene clusters has resulted in an explosion ... [more]

Toxic cyanobacteria pose a significant hazard to human health and the environment. The recent characterisation of cyanotoxin synthetase gene clusters has resulted in an explosion of molecular detection methods for these organisms and their toxins. Conventional polymerase chain reaction (PCR) tests targeting cyanotoxin biosynthesis genes provide a rapid and sensitive means for detecting potentially toxic populations of cyanobacteria in water supplies. The adaptation of these simple PCR tests into quantitative methods has additionally enabled the monitoring of dynamic bloom populations and the identification of particularly problematic species. More recently, DNA microarray technology has been applied to cyanobacterial diagnostics offering a high-throughput option for detecting and differentiating toxic genotypes in complex samples. Together, these molecular methods are proving increasingly important for monitoring water quality. Crown Copyright © 2008.

DOI 10.1016/j.copbio.2008.03.002
Citations Scopus - 89Web of Science - 71
Co-authors Brett Neilan
2008 Pearson LA, Moffitt MC, Ginn HP, Neilan BA, 'The molecular genetics and regulation of cyanobacterial peptide hepatotoxin biosynthesis', Critical Reviews in Toxicology, 38 847-856 (2008)

Over the last 10 years, we have witnessed major advances in our understanding of natural product biosynthesis, including the genetic basis for toxin production by numerous groups ... [more]

Over the last 10 years, we have witnessed major advances in our understanding of natural product biosynthesis, including the genetic basis for toxin production by numerous groups of cyanobacteria. Cyanobacteria produce an unparalleled array of bioactive secondary metabolites, including alkaloids, polyketides and non-ribosomal peptides, some of which are potent toxins. This review addresses the molecular genetics underlying the production of hepatotoxins, microcystin and nodularin in fresh and brackish water. These toxins pose a serious threat to human health and their occurrence in water supplies is increasing, because of the prevalence of toxic algal blooms worldwide. Toxin biosynthesis gene-cluster-associated transposition and the natural transformability of certain species suggest a broader distribution of toxic cyanobacterial taxa. The information gained from the discovery of these toxin biosynthetic pathways has enabled the genetic screening of various environments for drinking-water quality management. Understanding the role of cyanotoxins in the producing microorganisms and the environmental regulation of their biosynthesis genes may also suggest the means of controlling toxic-bloom events. Copyright © 2008 Informa UK Ltd.

DOI 10.1080/10408440802291513
Citations Scopus - 21Web of Science - 22
Co-authors Brett Neilan
2007 Pearson LA, Barrow KD, Neilan BA, 'Characterization of the 2-hydroxy-acid dehydrogenase McyI, encoded within the microcystin biosynthesis gene cluster of microcystis aeruginosa PCC7806', Journal of Biological Chemistry, 282 4681-4692 (2007)

The cyanobacterium Microcystis aeruginosa is widely known for its production of the potent hepatotoxin microcystin. This cyclic heptapeptide is synthesized non-ribosomally by the ... [more]

The cyanobacterium Microcystis aeruginosa is widely known for its production of the potent hepatotoxin microcystin. This cyclic heptapeptide is synthesized non-ribosomally by the thiotemplate function of a large modular enzyme complex encoded within the 55-kb microcystin synthetase gene (mcy) cluster. The mcy gene cluster also encodes several stand-alone enzymes, putatively involved in the tailoring and export of microcystin. This study describes the characterization of the 2-hydroxy-acid dehydrogenase McyI, putatively involved in the production of D-methyl aspartate at position 3 within the microcystin cyclic structure. A combination of bioinformatics, molecular, and biochemical techniques was used to elucidate the structure, function, regulation, and evolution of this unique enzyme. The recombinant McyI enzyme was overexpressed in Escherichia coli and enzymatically characterized. The hypothesized native activity of McyI, the interconversion of 3-methyl malate to 3-methyl oxalacetate, was demonstrated using an in vitro spectrophotometric assay. The enzyme was also able to reduce a-ketoglutarate to 2-hydroxyglutarate and to catalyze the interconversion of malate and oxalacetate. Although NADP(H) was the preferred cofactor of the McyI-catalyzed reactions, NAD(H) could also be utilized, although rates of catalysis were significantly lower. The combined results of this study suggest that hepatotoxic cyanobacteria such as M. aeruginosa PCC7806 are capable of producing methyl aspartate via a novel glutamate mutase-independent pathway, in which McyI plays a pivotal role. © 2007 by The American Society for Biochemistry and Molecular Biology, Inc.

DOI 10.1074/jbc.M606986200
Citations Scopus - 23Web of Science - 20
Co-authors Brett Neilan
2004 Pearson LA, Hisbergues M, Börner T, Dittmann E, Neilan BA, 'Inactivation of an ABC transporter gene, mcyH, results in loss of microcystin production in the cyanobacterium Microcystis aeruginosa PCC 7806', Applied and Environmental Microbiology, 70 6370-6378 (2004)

The cyanobacterium Microcystis aeruginosa is widely known for its production of the potent hepatotoxin microcystin. Microcystin is synthesized nonribosomally by the thiotemplate f... [more]

The cyanobacterium Microcystis aeruginosa is widely known for its production of the potent hepatotoxin microcystin. Microcystin is synthesized nonribosomally by the thiotemplate function of a large, modular enzyme complex encoded within the 55-kb microcystin synthetase (mcy) gene cluster. Also encoded within the mcy gene cluster is a putative ATP binding cassette (ABC) transporter, McyH. This study details the bioinformatic and mutational analyses of McyH and offers functional predictions for the hypothetical protein. The transporter is putatively comprised of two homodimers, each with an N-terminal hydrophobic domain and a C-terminal ATPase. Phylogenetically, McyH was found to cluster with members of the ABC-A1 subgroup of ABC ATPases, suggesting an export function for the protein. Two mcyH null mutant (¿mcyH) strains were constructed by partial deletion of the mcyH gene. Microcystin production was completely absent in these strains. While the mcyH deletion had no apparent effect on the transcription of other mcy genes, the complete microcystin biosynthesis enzyme complex could not be detected in ¿mcyH mutant strains. Finally, expression levels of McyH in the wild type and in ¿mcyA, ¿mcyB, and ¿mcyH mutants were investigated by using immunoblotting with an anti-McyH antibody. Expression of McyH was found to be reduced in ¿mcyA and ¿mcyB mutants and completely absent in the ¿mcyH mutant. By virtue of its association with the mcy gene cluster and the bioinformatic and experimental data presented in this study, we predict that McyH functions as a microcystin exporter and is, in addition, intimately associated with the microcystin biosynthesis pathway.

DOI 10.1128/AEM.70.11.6370-6378.2004
Citations Scopus - 130Web of Science - 127
Co-authors Brett Neilan
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Conference (3 outputs)

Year Citation Altmetrics Link
2008 Pearson LA, Hisbergues M, Boerner T, Dittmann E, Neilan BA, 'Inactivation of an ABC transporter, mcyH, results in loss of microcystin production in the cyanobacterium Microcystis aeruginosa PCC 7806', CYANOBACTERIAL HARMFUL ALGAL BLOOMS: STATE OF THE SCIENCE AND RESEARCH NEEDS, Research Triangle Park, NC (2008)
Co-authors Brett Neilan
2008 Roberts AA, Pearson LA, Copp JN, Neilan BA, 'Unnatural production of natural products: Heterologous expression and combinatorial biosynthesis of novel cyanobacterial-derived compounds', PLANTA MEDICA, Athens, GREECE (2008)
Co-authors Brett Neilan
2008 Neilan BA, Pearson LA, Moffitt MC, Mihali KT, Kaebemick M, Kellmann R, Pomati F, 'Chapter 17: The genetics and genomics of cyanobacterial toxicity', CYANOBACTERIAL HARMFUL ALGAL BLOOMS: STATE OF THE SCIENCE AND RESEARCH NEEDS, Research Triangle Park, NC (2008)
Citations Web of Science - 26
Co-authors Brett Neilan
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Dr Leanne Pearson-Neilan

Position

Senior Research Associate
School of Environmental and Life Sciences
College of Engineering, Science and Environment

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