About
Marilyn Anderson is Professor of Biochemistry at La Trobe University in Melbourne, where she leads research into plant biochemistry with a particular focus on cyclotide biosynthesis and plant defence. Her work has been fundamental to understanding how plants produce cyclotides at the molecular level — knowledge that underpins all efforts to engineer crop plants for pharmaceutical cyclotide production.
With an H-index of 67 and more than 13,700 citations across 162+ publications, Anderson is among the most highly cited plant biochemists in Australia. Her research has had direct commercial impact through Hexima Ltd, a spinout company she co-founded to apply her discoveries in plant defence to the development of transgenic pest-resistant crops.
Background & Career
Anderson's career has been centred at La Trobe University, where she built one of Australia's foremost plant biochemistry groups. Her interest in cyclic peptides emerged from a broader programme investigating how plants defend themselves against pathogens and pests — work that brought her into close collaboration with David Craik's group at the University of Queensland.
The collaboration between Anderson's molecular biology expertise and Craik's structural chemistry expertise proved enormously productive. Together their groups solved some of the most fundamental questions in cyclotide biology: how are cyclotide precursor proteins encoded? How does a plant convert a linear precursor into a circular protein? And where in the cell does this happen?
Anderson's particular contribution was the molecular biology side of these questions — the gene structure, the protein processing machinery, and the cellular localisation of cyclotide biosynthesis. These answers transformed cyclotides from a biochemical curiosity into a platform that could, in principle, be engineered into any plant.
Key Contributions
- Single-gene encoding of cyclotides: Demonstrated that cyclotides are encoded by individual genes — a remarkable finding for a cyclic protein from a eukaryotic organism, where multi-component biosynthetic pathways are the norm. This discovery meant cyclotide production could be transferred to other plants by introducing a single gene construct.
- Vacuolar cyclisation: Revealed that the head-to-tail cyclisation of cyclotide precursor proteins occurs in the plant vacuole — identifying the intracellular compartment and processing machinery responsible. This resolved a key mechanistic question and identified the asparaginyl endopeptidase (AEP/VPE) enzyme family as the likely cyclases.
- Cyclotide-like sequences in crop plants: Discovered cyclotide-like sequences in graminaceous crop plants including rice, maize, and wheat — plants that do not produce conventional cyclotides but encode related proteins. This finding suggested a far more ancient and widespread evolutionary origin for the cyclotide scaffold than had previously been assumed.
- Hexima Ltd: Co-founded Hexima Ltd, a plant biotechnology spinout applying Anderson's research on plant defence peptides to the development of transgenic crops with enhanced resistance to fungal pathogens and insect pests — without the need for chemical pesticides.
- Evolutionary and bioinformatic analysis: Made foundational contributions to understanding the evolutionary biology of plant cyclopeptides using bioinformatics and gene expression analysis, helping to reconstruct the evolutionary history of the cyclotide gene family across the plant kingdom.
The Biosynthesis Question
Understanding cyclotide biosynthesis was one of the central challenges of early cyclotide research. Cyclotides are proteins — they must be encoded in DNA, transcribed into RNA, translated on ribosomes, and then processed. But unlike conventional proteins, they have no free ends: they are head-to-tail circular. Somehow the plant must join the N-terminus of the mature peptide to its C-terminus after translation.
Anderson's work resolved this puzzle. Cyclotides are initially translated as larger linear precursor proteins — "pre-pro-cyclotides" — that contain the mature cyclotide sequence flanked by signal peptide and propeptide sequences. The plant's vacuolar processing enzyme (AEP/VPE) cleaves the precursor and simultaneously ligates the ends, producing the circular product. This "transpeptidation" reaction — cutting and joining in a single step — is now understood to be the key biosynthetic event, and it is also the inspiration for the enzyme-based cyclotide synthesis methods developed by James Tam's group (butelase-1).
Anderson's discovery that a single gene encodes a cyclotide, and that cyclisation occurs via a well-understood enzyme family in the vacuole, means the entire production system can be transferred to crop plants by genetic engineering. This is the molecular foundation of the plant pharming concept developed by Craik and others — and of commercial ventures like Phyllome.
Key Publications
Foundational biosynthesis paper establishing the vacuole as the site of cyclotide cyclisation and identifying the processing enzymes responsible.
Discovery paper reporting cyclotide-related sequences in rice, maize, and wheat — expanding the known taxonomic range of the cyclotide scaffold and suggesting deep evolutionary origins.
Comprehensive review article synthesising the molecular biology of cyclotide production — gene structure, precursor architecture, processing enzymes, and cellular localisation.
Anderson and Craik have co-authored more than 30 papers spanning cyclotide structure, biosynthesis, function, and pharmaceutical application — one of the most productive research collaborations in the field.