Marvin Miller

Research Interests

The primary interests in Professor Miller's laboratory are in synthetic and bioorganic chemistry. Most effort is directed toward the development of new methodology and its incorporation into the syntheses and study of biologically important compounds. Special emphasis is given to asymmetrical syntheses and studies of hydroxamic acid containing microbial iron transport agents (siderophores), amino acids, peptides, b-lactam antibiotics and carbocyclic analogs of antifungal and anticancer nucleosides. The group has completed the first syntheses of the siderophores aerobactin, arthorobactin, schizokinen, several mycobactins, foroxymithine and several analogs. Recent efforts have been directed toward the syntheses and study of siderophore-antibiotic conjugates in a program designed to develop iron transport-mediated drug delivery agents, including those with potential microbe-triggered release processes.

Much effort has addressed the syntheses of functionalized b-lactams, the core unit of an important class of antibiotics. The result has been the development of an efficient, and generally applicable, synthetic approach based on a biomimetic N-C4 closure. This process and subsequent chemistry has facilitated the synthesis of several novel antibiotics and b-lactamase inhibitors. The chemical versatility of the methods indicates that a variety of new b-lactams may be synthesized for studying important structure-activity relationships.

Recent studies of acylnitroso cycloadditions by oxidation of hydroxamic acids have led to the development of new methods for the asymmetric syntheses of a variety of biologically interesting compounds.

New chemical and enzymatic methodologies for the asymmetrical syntheses of other biologically important molecules are also being developed.

Selected Publications

• Lin, Y.-M.; Ghosh, M.; Miller, P.; Möllmann, U.; Miller, M. J. “Synthetic sideromycins (skepticism and optimism): selective generation of either broad or narrow spectrum Gram-negative antibiotics.” Biometals 2019, 32, 425-451.
• Ghosh, M.; Miller, P. A.; Miller, M. J. “Antibiotic Repurposing:  Bis-catechol- and Mixed Ligand (Bis-catechol-mono-hydroxamate)-Teicoplanin Conjugates are Active against Multi-Drug Resistant Acinetobacter baumannii.” Journal of Antibiotics 2020, 73, 152-157.
• Betoudji, F.; Rahman, T. A. E.; Miller, M. J.; Ghosh, M.; Jacques, M.; Bouarab, K.; Malouin, F. “A Siderophore Analog of Fimsbactin from Acinetobacter Hinders Growth of the Phytopathogen, Pseudomonas syringae and Induces Systemic Priming of Immunity in Arabidopsis thaliana.” Pathogens 2020, 9, 806. DOI:10.3390/pathogens9100806.
• Lee, B. S.; Hards. K.; Engelhart, C. A.; Hasenoehri, E. J.; Kalia, N. P.; Mackenzien, J. S.; Sviriaeva, E.; Chong, S. M. S.; Manimekalai, M. S. S.; Koh,, V. H.; Chan, J.; Xu, J.; Alonso, S.; Miller, M. J.; Steyn, A. J.; Grüber, G.; Schnappinger, D.; Berney, M.; Cook, G. M.; Moraski, G. C.; Pethe, K. “Dual inhibition of the terminal oxidases eradicates antibiotic‐tolerant Mycobacterium tuberculosis.” EMBO Molecular Medicine 2021, 13:e13207. DOI:10.15252/emmm.202013207
• Hopfner, S. M.; Lee, B. S.; Kalia, N. P.; Miller, M. J.; Pethe, K.; Moraski, G. C. “Structure guided generation of thieno[3,2-d] pyrimidin-4-amine Mycobacterium tuberculosis bd oxidase inhibitors.” RSC Medicinal Chemistry 2021, 12, 73-77.
• Liu, R.; Markley, L.; Miller, P. A.; Franzblau, S.; Shetye, G.; Ma, R.; Savkova, K.; Mikusova, K.; Lee, B. S.; Pethen, K.; Moraski, G. C.; Miller, M. J. “Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds.” RSC Medicinal Chemistry 2021, 12, 62-72.
• Miller, M. J.; Liu, R. “Design and Syntheses of New Antibiotics Inspired by Nature’s Quest for Iron in an Oxidative Climate.” Accounts of Chemical Research 2021. DOI:10.1021/acs.accounts.1c00004