Andrew Myers
· Amory Houghton Professor of Chemistry and Chemical BiologyVerifiedHarvard University · Chemistry
Active 1981–2025
About
Andrew G. Myers is the Amory Houghton Professor of Chemistry at Harvard University. He graduated from the Massachusetts Institute of Technology (MIT) in 1981 with a Bachelor of Science degree. His introduction to chemical research began as an undergraduate in the laboratory of Professor William R. Roush. He furthered his studies under the guidance of Professor E.J. Corey. The Myers Research Group focuses on advancing chemical research, as indicated by their active publication record and ongoing projects. Professor Myers's work includes significant contributions to the development of synthetic antibiotics capable of overcoming bacterial multidrug resistance, as exemplified by his co-authorship of a 2021 Nature publication on this topic.
Research topics
- Biology
- Microbiology
- Computer Science
- Artificial Intelligence
- Cell biology
- Chemistry
- Computational biology
- Genetics
- Biochemistry
- Medicine
Selected publications
Why sulfur is important in lincosamide antibiotics
Chem · 2025-03-07
articleOpen accessSenior authorDiscovery of a fluorinated macrobicyclic antibiotic through chemical synthesis
Nature Chemistry · 2025-03-07 · 4 citations
articleOpen accessSenior authorPractical Synthesis of Oxepanoprolines
Organic Process Research & Development · 2025-02-19 · 1 citations
articleSenior authorCorrespondingA new, more scalable route for the synthesis of the common oxepanoproline southern fragment of the antibiotic candidates iboxamycin, cresomycin, and BT-33 is presented. A key transformation in the route is a diastereoselective TiCl4-mediated conjugate addition of an allylsilane to an Evans N-acryloyloxazolidinone, followed by syn-aldol addition of the resultant titanium enolate to (R)-Garner’s aldehyde, which assembles all the stereocenters within the target molecule in a single operation.
A case of Scedosporium prolificans pulmonary infection in a patient with acute myeloid leukemia
Respiratory Medicine Case Reports · 2024-01-01 · 1 citations
articleOpen accessAn elderly woman with a history of myelodysplastic syndrome complicated by cavitary pneumonia treated with antibiotics and antifungal therapy was admitted with severe sepsis and pulmonary opacities on imaging. Pulmonary infection with Scedosporium prolificans , was diagnosed on bronchopulmonary lavage (BAL). This common environmental fungus is known to cause rare but severe infection in immunocompromised hosts. The patient was diagnosed with progression to acute myeloid leukemia during the hospitalization for which chemotherapy was initiated. Despite broadening antifungal therapy, the patient developed multi-organ system failure and died.
Discovery of a broad-spectrum, fluorinated macrobicyclic antibiotic through chemical synthesis
ChemRxiv · 2024-09-27 · 2 citations
preprintOpen accessSenior authorWe report the discovery through chemical synthesis of BT-33, a fluorinated macrobicyclic oxepanoprolinamide antibiotic. BT-33 potently inhibits the growth of multidrug-resistant clinical isolates of Gram-positive and Gram-negative bacteria and has an extended half-life in vivo relative to its predecessors cresomycin and iboxamycin. We report structure-activity relationships within the macrobicyclic substructure, which reveal structural features that are essential to the enhanced potency of BT-33 as well as its increased metabolic stability. We determine the structure of BT-33 in complex with the bacterial ribosome by X-ray crystallography, analysis of which suggests that the newly introduced fluorine atom makes an additional Van der Waals contact with nucleobase G2505. Finally, we show that the C7-methyl group of BT-33 rigidifies the macrocyclic ring in a conformation that is highly preorganized for ribosomal binding by using variable-temperature 1H-NMR experiments, density-functional theory calculations, and vibrational circular dichroism spectroscopy to compare macrobicyclic homologs of BT-33 and a C7-desmethyl analog.
Structural basis of Cfr-mediated antimicrobial resistance and mechanisms to evade it
Nature Chemical Biology · 2024-01-18 · 24 citations
articleOpen accessAn antibiotic preorganized for ribosomal binding overcomes antimicrobial resistance
Science · 2024-02-15 · 70 citations
articleOpen accessSenior authorCorrespondingWe report the design conception, chemical synthesis, and microbiological evaluation of the bridged macrobicyclic antibiotic cresomycin (CRM), which overcomes evolutionarily diverse forms of antimicrobial resistance that render modern antibiotics ineffective. CRM exhibits in vitro and in vivo efficacy against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains of Staphylococcus aureus , Escherichia coli , and Pseudomonas aeruginosa . We show that CRM is highly preorganized for ribosomal binding by determining its density functional theory–calculated, solution-state, solid-state, and (wild-type) ribosome-bound structures, which all align identically within the macrobicyclic subunits. Lastly, we report two additional x-ray crystal structures of CRM in complex with bacterial ribosomes separately modified by the ribosomal RNA methylases, chloramphenicol-florfenicol resistance (Cfr) and erythromycin-resistance ribosomal RNA methylase (Erm), revealing concessive adjustments by the target and antibiotic that permit CRM to maintain binding where other antibiotics fail.
Journal of Global Antimicrobial Resistance · 2024-09-16 · 1 citations
articleOpen access• New synthetic lincosamides, iboxamycin and cresomycin, display potent in vitro activity against ocular methicillin-resistant Staphylococcus aureus (MRSA) isolates. • Both drugs are active against widespread MRSA clonal complexes CC8 and CC5. • The in vitro potencies of iboxamycin and cresomycin are not impacted by multidrug-resistance phenotypes or by the presence of erm genes when compared with clindamycin. Antimicrobial resistance is a global pandemic that poses a major threat to vision health as ocular bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA), are becoming increasingly resistant to first-line therapies. Here we evaluated the antimicrobial activity of new synthetic lincosamides in comparison to currently used antibiotics against clinical ocular MRSA isolates. Antimicrobial susceptibility testing was performed by broth microdilution for two novel synthetic lincosamides (iboxamycin and cresomycin) and eight comparator antibiotics against a collection of 50 genomically characterised ocular MRSA isolates, including isolates harbouring erm genes ( n = 25). Both drugs were active against widespread MRSA clonal complexes CC8 and CC5. The MIC 50 and MIC 90 of iboxamycin were 0.06 and 2 mg/L, respectively. Cresomycin (MIC 50 = 0.06 mg/L) also displayed good activity with an in vitro potency four-fold higher (MIC 90 = 0.5 mg/L) than iboxamycin. In isolates harbouring erm genes, MIC 90 were >16, 2, and 0.5 mg/L for clindamycin, iboxamycin, and cresomycin, respectively. The in vitro potencies of iboxamycin and cresomycin were similar or higher than that of comparator agents and were not impacted by multidrug-resistance phenotypes or by the presence of erm genes when compared with clindamycin. Our results demonstrate that iboxamycin and cresomycin display potent in vitro activity against ocular MRSA isolates, including multidrug-resistant isolates harbouring erm genes.
Practical Synthesis of Macrobicyclic Thiolincosamines
Journal of the American Chemical Society · 2024-10-12 · 2 citations
articleOpen accessSenior authorCorrespondingScalable syntheses of the northern macrobicyclic thiolincosamine fragments of two structurally complex antibiotic candidates, BT-33 and cresomycin, are presented. A key transformation in each route is the highly diastereoselective addition of a putative allenylzinc nucleophile to a common Ellman sulfinimine intermediate using a zinc-promoted Barbier-type propargylation protocol that is detailed herein. These transformations proceed with dynamic kinetic resolution and use just 1.2 equiv of each respective propargyl bromide precursor.
The Journal of Organic Chemistry · 2023-01-17 · 1 citations
articleOpen accessSenior authorCorrespondingThe regioselectivity of a [3+2] dipolar cycloaddition reaction of a stabilized azomethine ylide with an electron-deficient dipolarophile was found to be counter to a report published in this journal.
Recent grants
Discovery through chemical synthesis of antibiotics effective against modern bacterial pathogens
NIH · $3.8M · 2022–2027
NIH · $463k · 1993
NIH · $3.0M · 2011
New Reactions and Strategies in Synthesis
NSF · $510k · 2008–2011
New Reactions and Strategies in Synthesis
NSF · $509k · 2012–2016
Frequent coauthors
- 17 shared
Kelvin J. Y. Wu
Harvard University Press
- 17 shared
Ziyang Zhang
Tsinghua University
- 16 shared
Daniel W. Kung
Pfizer (United States)
- 16 shared
James L. Gleason
McGill University
- 16 shared
Mohammad Movassaghi
Massachusetts Institute of Technology
- 13 shared
Ian B. Seiple
University of California, San Francisco
- 13 shared
Soojin Kwon
North Carolina State University
- 13 shared
Vasili Hauryliuk
University of Tartu
Labs
Andrew G Myers Research GroupPI
Research Interests Andrew G. Myers graduated from MIT in 1981 with a Bachelor of Science degree. He was introduced to chemical research as an undergraduate in the laboratory of Professor William R. Roush, and went on to study with Professor E.J. Corey...
Education
- 2005
Ph.D., Chemistry
Harvard University
- 2000
B.S., Chemistry
University of California, Berkeley
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