This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The evolution of plant forms from an aquatic to a land base was accompanied by formation of a vast plethora of phenolic components in the vascular plants, of which the lignins, lignans and monoterpene are the most abundant. Together they play important roles in plant defense and cell wall reinforcement, such as with the lignans having antimicrobial, antifungal, antiviral and antioxidant properties, whereas the lignins have structural roles in support of vascular apparatus integrity. Some lignans and monoterpene derivatives find widespread application in cancer treatment, e.g., the podophyllotoxin derivatives, teniposide, etoposide, etopohos and taxol which are used in treatment of germinal testicular and small cell lung cancers, and for certain forms of leukemia. Others,such as enterodiol/enterolactone, are believed to have cancer-preventing properties and are formed through dietary ingestion of lignans (and possibly lignin) precursors. The goal of this project is thus to define the structure function relationships of these key proteins and enzymes in lignan, lignin and monolignol biosynthesis through high resolution X-ray structural analyses. We describe and compare what is now known about the mechanistic (regiospecificity and enantiospecificity) basis of the lignan pathway enzymes, pinoresinol-lariciresinol reductase and secoisolariciresinol dehydrogenase as well as of various monolignol pathway enzymes (e.g., cinnamyl alcohol dehydrogenase, arylpropenal double bond reductase, cinnamoyl CoA reductase, etc.) The information gained from these studies will be very useful for exploring the regulation of phenylpropanoid biosynthesis for ecological plant protection, and for the industrial-scale regiospecific and stereospecific synthesis of these pharmacologically active substances.
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