Dr Hanna Kwon

Haem and iron homeostasis

My group uses structural biology and mechanistic enzymology to understand how metal-dependent proteins, especially haem proteins, carry out and regulate essential biology. Haem enables redox chemistry such as oxygen activation and electron transfer, but because it can also be damaging when mismanaged, cells tightly control haem and iron homeostasis through regulated haem binding, trafficking and turnover. We are interested in the structural and mechanistic principles that govern haem binding, positioning, and reactivity, as well as the regulated handling of haem to support haem and iron homeostasis. This includes work on enzymes that form transient intermediates during catalysis, and on haem-responsive systems that help cells adapt when haem availability (or haem stress) changes.

Secondary metabolites and antimicrobial enzyme chemistry

Building on this foundation, we are expanding into enzyme chemistry from microbial secondary metabolism. Specialised biosynthetic pathways produce chemically diverse metabolites, including molecules with antimicrobial activity, and we are interested in how enzymes achieve the selectivity needed to build these structures. One example is oxygenase chemistry, including non-haem Fe(II)/2-oxoglutarate oxygenases, which can catalyse highly selective oxidations in natural product pathways. By linking enzyme mechanism to product outcome, this work aims to open opportunities in biocatalyst development and the discovery or diversification of bioactive metabolites.

Across both areas, we combine X-ray and neutron crystallography, cryo-electron microscopy, and time-resolved crystallography/spectroscopy to capture protein motions and short-lived intermediates that underpin function, including experiments at large-scale facilities such as Diamond Light Source.

Current project themes include:

Haem sensing and gene regulation in pathogens, where haem-responsive transcription factors switch DNA binding on/off to balance haem uptake, use, and efflux—highlighting potential anti-virulence targets. 

Microbial secondary metabolism and antimicrobial activity, including discovery of new peptide natural products (RiPPs) and the enzymes that build them—expanding the biocatalysis toolbox and enabling sustainable routes to high-value molecules. 

Oxygenase mechanism and selectivity in antibiotic biosynthesis, for example non-heme Fe(II)/2-oxoglutarate enzymes that perform highly selective hydroxylations and can be engineered for greener synthesis of valuable building blocks.

Haem dioxygenases in health and disease (e.g., IDO/TDO), using time-resolved crystallography and spectroscopy to define how O₂ is activated at haem and how stress or binding partners tune activity.