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Department of Chemistry College of Liberal Arts and Sciences

Research

Our research is currently supported by the NIH (R35 GM142574) and NSF (CHE 2440573)

Natural Product Discovery and Biosynthesis

We use genome mining to discover novel natural products from bacteria, understand how they are made in nature, and how they can be utilized and engineered for human health.

Recent Related Publications

Pie chart titled "TS Library (diterpene active/total number)" showing diterpene activity across bacterial phyla, a bar chart comparing diterpene counts from literature and this study for selected phyla, and two diterpene chemical structures.

Wei, X.; Ning, W.; et al. Exploring and expanding the natural chemical space of bacterial diterpenes. Nat. Commun. 2025, 16, 3721.

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Diagram showing the heterologous expression of *pla* genes in *Streptomyces*, detailing *plaT4* (GGPP synthase), *plaT3* (UbiA prenyltransferase), *plaT2* (Type II terpene synthase), and *plaT1* (Flavin-dependent monooxygenase) in the fungal meroterpenoid-like scaffold assembly from GGPP.

Alsup, T. A.; et al. Early-stage biosynthesis of phenalinolactone diterpenoids involves sequential prenylation, epoxidation, and cyclization. RSC Chem. Biol. 2024, 5, 1010–1016.

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The *Streptomyces albireticuli* alb gene cluster (albG-albP2) is depicted, along with a biosynthetic pathway showing sequential enzymatic transformations. AlbU catalyzes eunicellane isomerization, AlbP1 performs an innate P450 reaction, and AlbP2* performs a restored P450 reaction followed by oxy-Cope and reduction.

Li, Z.; et al. Cryptic isomerization in diterpene biosynthesis and the restoration of an evolutionarily defunct P450. J. Am. Chem. Soc. 2023, 145, 22361–22365.

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Mechanistic Enzymology

The biosynthesis of natural products requires powerful enzymes with exquisite control. We focus on revealing the mechanisms of two families of terpenoid biosynthetic enzymes: terpene synthases and cytochromes P450.

Recent Related Publications

Chemical mechanism depicting Myxobacterial terpene synthase (TiqS) converting GGPP to a tetraisohinane skeleton via deprotonation/reprotonation and a non-classical carbocation. An F81L mutation leads to a mutation-induced bifurcation product.

Wei, X.; et al. Avoidance of secondary carbocations, unusual deprotonation, and non-statistical dynamic effects in the cyclization mechanism of the 5/5/5/5-tetracyclic tetraisoquinane skeleton. J. Am. Chem. Soc. 2025, 147, 16293–16300.

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Diagram showing the enzyme AlbS (diterpene synthase) forming two products. Albireticule is shown with "Mechanism via" indicated, and prenylgermacrene A is associated with "Mutagenesis Labeling DFT Calculations".

Li, Z.; et al. First trans-eunicellane terpene synthase in bacteria. Chem 2023, 9, 698–708.

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Molecular model of GGPP bound in a protein active site, with surrounding residues D296, Y489, G485, H180, and Y329. The wild-type G485 and mutated G485D are highlighted.

Stowell, E. A.; et al. Structure-guided product determination of the bacterial type II diterpene synthase Tpn2. Commun. Chem. 2022, 5, 146.

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Biocatalysis

Once we understand how enzymes work, we develop them into biocatalysts, providing simpler and greener routes to commercially relevant materials.

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Recent Related Publications

Graphical abstract showing the biotransformation of a tetracyclic compound by Streptomyces, as indicated by the text "Biotransformation in Streptomyces" and images of microbial cultures. The starting material is on the left, leading to three different product structures with modifications on the right.

McCadden, C. A.; et al. Biocatalytic diversification of abietic acid in Streptomyces. J. Ind. Microbial. Biotechnol. 2025, 52, kuaf003.

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Diagram showing a Bacterial Diterpene Synthase catalyzing two reactions: "Cyclization of Native Substrate" (GGPP to Diterpenes) and "Prenylation via Substrate 'Decoy'" (Shorter R-PP & Nucleophile to Prenylated products).

Xu, B.; et al. Mutation of the eunicellane synthase Bnd4 alters its product profile and expands its prenylation ability. Org. Biomol. Chem. 2022, 20, 8833–8837.

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Fun Collaborations

Science is always most fun with friends! Combining knowledge, skills, and viewpoints often leads to a deeper understanding of the science and the most impactful findings.

Recent Related Publications

Biosynthetic pathway for atolypenes, showing the enzymatic conversion of GFPP through epoxidation (AtoF), prenylation (AtoD), transamination (AtoB), cyclization (AtoE with Glu314), and oxidation steps to form Atolypene E and Atolypene A.

Wang, Z.; et al. Biosynthesis of a bacterial meroterpenoid reveals a non-canonical class II meroterpenoid cyclase. Chem. Sci. 2025, 16, 310–317.

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Radial phylogenetic tree illustrating evolutionary relationships between Acariformes (magenta), Collembola (green), Bacteria (blue), and Fungi (light blue), with specific clades S1 and S2 marked.

Chen, X.; et al. Canonical terpene synthases in arthropods: Intraphylum gene transfer. Proc. Natl. Acad. Sci. 2024, 121, e2413007121.

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Experiment for *A. alliaceus* showing fungal cultures grown in No Salt, Instant Ocean®, NaBr, and NaI media, with a PCA plot displaying metabolic profiles and structures of the resulting brominated anthraquinone natural products.

Mandelare, P. E.; et al. Chemical diversity of Aspergillus alliaceus phenotypes: discovery of brominated bianthrones with activity against triple-negative breast cancer cell lines. ChemBioChem. 2024, 25, e202400398.

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