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Mathematics and Physical Science Category ─ Sunney I. Chan

Cracking the Mystery of Methane Oxidation in a Membrane Protein and Inventing a Molecular Catalyst

Sunney Chan Has Inspired Countless Talented Minds for the Love of Science and Humanity

In the 60 years of his scientific research career, Sunney I. Chan has navigated the fields of physical chemistry, chemical physics and biophysics. His research achievements are as broad as they are essential, cracking one black box after another in basic science. Every 20 years, he would come up with a ground-breaking discovery that takes the study of biological systems to a new epoch.

Sunney Chan is best known for developing and applying innovative spectroscopic and biophysical methods to solve fundamental problems on the structure and dynamics of membranes, nucleic acids and proteins, especially membrane proteins and metalloproteins of biological importance. To the general public, these terms may appear abstruse and unfamiliar, but his findings are like torches illuminating the dark, unknown territories, and paving the way to many more important discoveries in basic and applied science.

Ended Scientific Debate by Discovering ‘Vertical Interactions’ between Nucleic Acid Bases

In the early 1960s, Sunney Chan used nuclear magnetic resonance (NMR) spectroscopy to study the stacking of nucleic acid bases in aqueous solution. At that time, scientists around the world were still debating whether or not ‘horizontal’ interactions of hydrogen bonds in nucleic acid were sufficient to account for the stability of the structure of the DNA double helix at room temperature. In pioneering NMR experiments undertaken during 1962-64, Sunney Chan established that in a water solution, there exist strong ‘vertical’ interactions between the nucleic acid bases in DNA, and the nucleic acid bases stack in water in order to minimize the disruption of the hydrogenbonded network structure of the water, now commonly referred to as the ‘hydrophobic effect’. Consequently, this discovery of his brought to an end the scientific debate on why and how the Watson-Crick A-T and G-C base pairs can be formed in water.

Cracking the Myth of Cytochrome c Oxidase: A Redox-Linked Proton Pump

One of Sunney Chan’s most significant scientific researches is his probing of membrane proteins, particularly membrane-bound metalloenzymes, using novel biophysical methods to unravel the structures, functions, and kinetic behavior of these important molecular machines. His work on cytochrome c oxidase from bovine heart mitochondria was pioneering and elegant. In the late 1970s, Sunney Chan became the world authority in this field and his laboratory was particularly well known for the many original and insightful contributions elucidating the structure and function of this complex and important enzyme system.

Cytochrome c oxidase is an electron-driven proton pump, important for establishing the protomotive force obligatory for ATP synthesis in the mitochondrion. However, cytochrome c oxidase was a ‘black box’ for scientists at that time. Sunney Chan’s laboratory carried out decisive experiments during the early 1980s to delineate the ligand structures of the metal cofactors. With this structural information, Sunney Chan and his students established the rules on how the electrons and protons must be gated by redox linkage between the metal cofactors and the protein scaffold during proton pumping in order to kinetically control the flow of electrons and the coupled movement of the protons uphill against the protomotive force across the inner membrane of the mitochondrion.

How pMMO Converts Methane into Methanol: A Tripcopper Cluster at the Catalytic Center

In the early 1990s, Sunney Chan initiated a new venture directed toward understanding how methane is converted into methanol with high efficiency by the particulate monooxygenase (pMMO). Before moving to Academia Sinica in Taiwan, his laboratory at Caltech had succeeded in isolating and purifying the pMMO to homogeneity. He continued this research in Taiwan. During the 2000s, Sunney Chan’s Taiwan team developed novel methods to characterize the enzyme in depth and established the nature and identity of the copper cofactors in the protein, and discovered that a tricopper cluster is the critical element in the catalytic mechanism. This discovery is regarded one of the holy grails in organic chemistry. In recent years, Sunney Chan’s team at Academia Sinica and National Taiwan University has successfully developed the first molecular catalyst capable of efficient conversion of methane into methanol by O2 at room temperature. This marks a breakthrough milestone in methane oxidation. Today, with net zero carbon and decarbonization becoming the world’s most urgent mission, reducing methane emissions will help slow down global warming, and Sunney Chan’s discovery is more significant than ever.

As further evidence of his broad interests and research activities, Sunney Chan also devoted several years to understanding protein folding, an essential process in biosystems that creates muscles, hormones, enzymes, etc. It was one of biology’s biggest mysteries to be solved. Sunney Chan developed the use of caged compounds to study the very early events in protein folding initiated in the absence of denaturants. This work has demonstrated the importance of kinetic channeling in protein folding.

On top of his academic brilliance, Sunney Chan’s career is also marked by his love of humanity. As a teenager, he once vowed to join the priesthood. After gaining world-class recognition as a scientist, he stepped out of American science from one of the world’s most prestigious research institution-Caltech, and came to Taiwan to devote himself to building paradigms and infrastructures of advanced research for the then still-developing Academia Sinica. He was like a missionary spreading his faith. During his tenure as Vice President of Academia Sinica, he formulated a roadmap for the Genomics Research Center; he also worked with the National Science Council of Taiwan in creating the National Research Program in Genomics Medicine. Both have laid solid foundation for the booming of Taiwan’s applied medicine and biotechnology industry.

The TIGP (Taiwan International Graduate Program) in Academia Sinica was founded by Sunney Chan with an aim to attract global talents to undertake their graduate training in Taiwan. TIGP was established 20 years ago and it remains one of the most successful programs in Academia Sinica for the diversity and enrichment it has brought.

Leveraging his academic connections, Sunney Chan invited internationally-recognized researchers to lecture in Taiwan, significantly elevating Taiwan’s worldwide visibility and academic strengths. Over the years, he has organized many international symposia on cutting edge research in the frontiers of many fields, including chemical biology, biocatalysis and chemical catalysis, and energy, fuels, and sustainability. He is a visionary scientist with a keen sense of the directions that science is moving toward.

Sunney Chan was applauded by his fellow academicians for his selfless devotion in training young talents. He moved his research projects to Taiwan two decades ago and have since mentored hundreds of students: postdocs, graduate and undergraduate students. Among them, at least 25 from Taiwan are currently working in academic and research institutions, such as Ohio State University in the US and Max Planck Institute of Molecular Biology in Freiburg, Germany. Sunney Chan retired 10 years ago and still carries on his mission as a scientist and an educator. To this date, he continues to inspire many young minds in Taiwan and abroad, passing on his inheritance as valuable assets for generations to come.