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Joseph P. Noel

 

Joseph P. Noel

Joseph P. Noel

Investigator, Howard Hughes Medical Institute, Professor & Director, The Jack H. Skirball Center for Chemical Biology and Proteomics
Adjunct Professor, Department of Chemistry and Biochemistry, University of California, San Diego

"Most people are familiar with the word biodiversity, but 'chemodiversity'–the extraordinary tapestry of natural chemicals found in all organisms–is just as important for life and the survival of many different ecosystems on the earth. I am particularly interested in the chemical systems or biosynthetic pathways that give rise to these vital molecules."

Trying to make the best of their real estate, plants dispatch an impressive arsenal of small molecules to communicate and interact with the outside world. Among them, terpenes– the oldest and probably most widespread group of natural products synthesized by plants–play a particularly important role. Examples of common terpenes are pine resins and the essential oils of myrrh, rosemary, and thyme, but two of the best-known terpenes are probably cholesterol and taxol.

Despite their extraordinary diversity, all terpenes are assembled from the same five-carbon isoprene building blocks and then modified by an armada of terpene synthases in thousands of ways. Despite the great variety in the terpene synthases' substrate and product specificity, each enzyme falls squarely into one of two camps: cisoid or transoid, depending on how they prefer their raw material spatially configured. As a general rule, terpene synthases only produce cisoid products from cisoid substrates and transoid products from transoid substrates. In a recent study, however, Noel and his team discovered a notable exception: the transoid tobacco sesquiterpene synthase, which is in charge of catalyzing the first step in the biosynthesis of capsidiol, the main component of tobacco's natural antifungal chemical defense.

When fed a non-natural (cis, trans) version of the enzyme's natural (trans, trans) substrate, the enzyme very efficiently converted the alternative substrate into a new compound with a complex chemical structure and a pleasant woody scent. This finding hinted that the so-called non-natural version of the enzyme's substrate may not be so non-natural after all. In fact, there is now evidence that it is made in small amounts in all living systems. During its evolutionary history, this particular plant enzyme may have taken advantage of the presence of this alternative substrate to produce a new chemical, with a function selected for during the course of evolution. With the compound now in hand, the search for its role in the plant is under way. Nevertheless, this new compound not only might be of great interest to the fragrance industry, it could become an important starting point for the development of new pharmaceuticals to treat disease.

Lab Photo

Left to right:
Back row: Jing-Ke Weng, Nikki Dellas, June Brennan, Gordon Louie, Marianne Bowman, Kyle Merchant, Justin Pacheco, Tom Baiga

Front row: Ryan Philippe, Charisse Crenshaw, Yongxia Guo, Joseph Noel, Greg Macias, Charles Stewart, Hyun Jo Koo

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Joseph P. Noel

Faculty

Joseph P. Noel

Joseph P. Noel

Investigator, Howard Hughes Medical Institute, Professor & Director, The Jack H. Skirball Center for Chemical Biology and Proteomics
Adjunct Professor, Department of Chemistry and Biochemistry, University of California, San Diego

 

Mechanistic and Structural Basis for Plant Metabolic Evolution

What shapes natural selection of specialized enzymes and metabolic pathways underlying the emergence and expansion of chemical diversity in living systems remains a fundamental yet largely unanswered question in evolutionary biology. For sessile organisms possessing the developmental and ecological complexity of plants, this adaptive process is especially critical to their survival. The chemical output of these metabolic pathways serve as key mediators of intra- and interspecies interactions resulting in speciation, survival and ecological homeostasis. Specifically, we seek to understand and infer as best as possible the adaptive molecular changes that have occurred in plant specialized metabolism as these enzyme systems emerged and subsequently evolved from their ancestral roots in primary metabolism at the dawn of terrestrial plants nearly 500 millions ago.

Early land plants arose from freshwater ecological niches. Their success on land, driven by evolutionary adaptations such as their ability to screen out damaging UV radiation, their adeptness at resisting desiccation and their mastery of self-support and fluid conduction, had far-reaching consequences for the complexity of terrestrial ecosystems that followed this defining event on the terrestrial earth. Land plant early success and the ongoing diversification of the green plant lineage was then and is to this day due in large part to their ability to biosynthesize specialized or so-called secondary metabolites.

Through photosynthesis, early land plants provided major nutritional stores that precipitated the dawn and development of almost all the early terrestrial life forms, including tetrapods, insects, fungi and even microorganisms. In turn, the rise of land plants profoundly impacted the global climate. For example, carbon fixation by early land plants is considered one of the major factors that led to the significant drop of atmospheric CO2 levels and a corresponding increase of O2 levels during the late Palaeozoic era. These changes in atmospheric composition, in turn, precipitated more physiological innovations, e. g. the evolution of aerial locomotion in insects and the origin of megaphyll leaves in plants.

Given the momentous contribution of plant specialized metabolism to the biodiversity of the terrestrial earth, specialized metabolic pathways and their "chemical output" present us with a rich evolutionary record of where biosynthetic pathways, natural chemicals and biosynthetic enzymes have been (vestigial biochemical traits), what adaptive advantages these complex enzymatic systems hold in the present (emergent function), and ultimately where these pathways may be heading in the future (functional plasticity).

Our decade-long study of these metabolic pathways has coalesced around four fundamental questions regarding the origin of specialized metabolism during land plant evolution. (i) Can one discern the phylogenetic routes through which plant secondary metabolic enzymes evolved from their primary metabolic ancestors? (ii) What are the biophysical features inherited by these enzymes that give rise to evolvability and/or restrain such evolutionary processes? (iii) How was the evolutionary directionality maintained if at all before the emergence of the defining activities that provided obvious selective advantages? (iv) What role did catalytic promiscuity play in shaping the evolvability of these biosynthetic systems? Answering these questions not only will extend our understanding of the biochemical strategies that early land plants adopted in their adaptation to a myriad of terrestrial environments, but will also better shape our appreciation of mutability and the origins of new enzyme function in general. Our work examines the evolution, biology, biochemistry and chemistry underlying the biosynthesis of plant natural products including isoprenoids, phenylpropanoids, polyketides and associated flavonoids and fatty acid-derived metabolites.

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(bold denotes member or former member of Noel laboratory)

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