Justin J. Maresh

Bio: Justin J. Maresh is an academic researcher from DePaul University. The author has contributed to research in topics: Indole test & Agrobacterium tumefaciens. The author has an hindex of 9, co-authored 14 publications receiving 1182 citations. Previous affiliations of Justin J. Maresh include Massachusetts Institute of Technology & Emory University.

Strictosidine synthase: mechanism of a Pictet-Spengler catalyzing enzyme.

Abstract: The Pictet−Spengler reaction, which yields either a β-carboline or a tetrahydroquinoline product from an aromatic amine and an aldehyde, is widely utilized in plant alkaloid biosynthesis. Here we deconvolute the role that the biosynthetic enzyme strictosidine synthase plays in catalyzing the stereoselective synthesis of a β-carboline product. Notably, the rate-controlling step of the enzyme mechanism, as identified by the appearance of a primary kinetic isotope effect (KIE), is the rearomatization of a positively charged intermediate. The KIE of a nonenzymatic Pictet−Spengler reaction indicates that rearomatization is also rate-controlling in solution, suggesting that the enzyme does not significantly change the mechanism of the reaction. Additionally, the pH dependence of the solution and enzymatic reactions provides evidence for a sequence of acid−base catalysis steps that catalyze the Pictet−Spengler reaction. An additional acid-catalyzed step, most likely protonation of a carbinolamine intermediate, i...

Silencing of tryptamine biosynthesis for production of nonnatural alkaloids in plant culture

Abstract: Natural products have long served as both a source and inspiration for pharmaceuticals. Modifying the structure of a natural product often improves the biological activity of the compound. Metabolic engineering strategies to ferment "unnatural" products have been enormously successful in microbial organisms. However, despite the importance of plant derived natural products, metabolic engineering strategies to yield unnatural products from complex, lengthy plant pathways have not been widely explored. Here, we show that RNA mediated suppression of tryptamine biosynthesis in Catharanthus roseus hairy root culture eliminates all production of monoterpene indole alkaloids, a class of natural products derived from two starting substrates, tryptamine and secologanin. To exploit this chemically silent background, we introduced an unnatural tryptamine analog to the production media and demonstrated that the silenced plant culture could produce a variety of novel products derived from this unnatural starting substrate. The novel alkaloids were not contaminated by the presence of the natural alkaloids normally present in C. roseus. Suppression of tryptamine biosynthesis therefore did not appear to adversely affect expression of downstream biosynthetic enzymes. Targeted suppression of substrate biosynthesis therefore appears to be a viable strategy for programming a plant alkaloid pathway to more effectively produce desirable unnatural products. Moreover, although tryptamine is widely found among plants, this silenced line demonstrates that tryptamine does not play an essential role in growth or development in C. roseus root culture. Silencing the biosynthesis of an early starting substrate enhances our ability to harness the rich diversity of plant based natural products.

Chemistry and Biology of Monoterpene Indole Alkaloid Biosynthesis

Abstract: Covering: up to 2006 Monoterpene indole alkaloids exhibit a diverse array of structures and biological activities. The biosynthetic pathways for several representative terpene indole alkaloids are described in detail.

Chemical biology of multi-host/pathogen interactions: chemical perception and metabolic complementation.

Abstract: The xenognostic mechanisms of two multi-host pathogens, the causative agent of crown gall tumors Agrobacterium tumefaciens and the parasitic plant Striga asiatica, are compared. Both organisms are general plant pathogens and require similar information prior to host commitment. Two mechanistic strategies, chemical perception and metabolic complementation, are used to ensure successful host commitment. The critical reactions at host-parasite contact are proton and electron transfer events. Such strategies may be common among multi-host pathogens.

The Role of Root Exudates in Rhizosphere Interactions with Plants and Other Organisms

Abstract: The rhizosphere encompasses the millimeters of soil surrounding a plant root where complex biological and ecological processes occur. This review describes recent advances in elucidating the role of root exudates in interactions between plant roots and other plants, microbes, and nematodes present in the rhizosphere. Evidence indicating that root exudates may take part in the signaling events that initiate the execution of these interactions is also presented. Various positive and negative plant-plant and plant-microbe interactions are highlighted and described from the molecular to the ecosystem scale. Furthermore, methodologies to address these interactions under laboratory conditions are presented.

Root exudate metabolites drive plant-soil feedbacks on growth and defense by shaping the rhizosphere microbiota

Abstract: By changing soil properties, plants can modify their growth environment. Although the soil microbiota is known to play a key role in the resulting plant-soil feedbacks, the proximal mechanisms underlying this phenomenon remain unknown. We found that benzoxazinoids, a class of defensive secondary metabolites that are released by roots of cereals such as wheat and maize, alter root-associated fungal and bacterial communities, decrease plant growth, increase jasmonate signaling and plant defenses, and suppress herbivore performance in the next plant generation. Complementation experiments demonstrate that the benzoxazinoid breakdown product 6-methoxy-benzoxazolin-2-one (MBOA), which accumulates in the soil during the conditioning phase, is both sufficient and necessary to trigger the observed phenotypic changes. Sterilization, fungal and bacterial profiling and complementation experiments reveal that MBOA acts indirectly by altering root-associated microbiota. Our results reveal a mechanism by which plants determine the composition of rhizosphere microbiota, plant performance and plant-herbivore interactions of the next generation.

The Pictet–Spengler Reaction in Nature and in Organic Chemistry

Abstract: Alkaloids are an important class of natural products that are widely distributed in nature and produced by a large variety of organisms. They have a wide spectrum of biological activity and for many years were used in folk medicine. These days, alkaloids also have numerous applications in medicine as therapeutic agents. The importance of these natural products in inspiring drug discovery programs is proven and, therefore, their continued synthesis is of significant interest. The condensation discovered by Pictet and Spengler is the most important method for the synthesis of alkaloid scaffolds. The power of this synthesis method has been convincingly proven in the construction of stereochemicaly and structurally complex alkaloids.

Natural Products Version 2.0: Connecting Genes to Molecules

Abstract: Natural products have played a prominent role in the history of organic chemistry, and they continue to be important as drugs, biological probes, and targets of study for synthetic and analytical chemists. In this Perspective, we explore how connecting Nature's small molecules to the genes that encode them has sparked a renaissance in natural product research, focusing primarily on the biosynthesis of polyketides and non-ribosomal peptides. We survey monomer biogenesis, coupling chemistries from templated and non-templated pathways, and the broad set of tailoring reactions and hybrid pathways that give rise to the diverse scaffolds and functionalization patterns of natural products. We conclude by considering two questions: What would it take to find all natural product scaffolds? What kind of scientists will be studying natural products in the future?