Michael A Fischbach

Summary

Publications

  1. pmc Eating for two: how metabolism establishes interspecies interactions in the gut
    Michael A Fischbach
    Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA
    Cell Host Microbe 10:336-47. 2011
  2. pmc Antibiotics for emerging pathogens
    Michael A Fischbach
    Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 325:1089-93. 2009
  3. pmc Antibiotics from microbes: converging to kill
    Michael A Fischbach
    Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Curr Opin Microbiol 12:520-7. 2009
  4. pmc Combination therapies for combating antimicrobial resistance
    Michael A Fischbach
    Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94158, USA
    Curr Opin Microbiol 14:519-23. 2011
  5. pmc The next frontier of systems biology: higher-order and interspecies interactions
    Michael A Fischbach
    Department of Bioengineering and Therapeutic Sciences and California Institute of Quantitative Biosciences, University of California, San Francisco, CA 94158, USA
    Genome Biol 11:208. 2010
  6. pmc The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis
    Rebecca A Butcher
    Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:1506-9. 2007
  7. pmc Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:11951-6. 2007
  8. pmc The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:16502-7. 2006
  9. ncbi request reprint Bromoenterobactins as potent inhibitors of a pathogen-associated, siderophore-modifying C-glycosyltransferase
    Hening Lin
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 128:9324-5. 2006
  10. pmc Biosynthetic tailoring of microcin E492m: post-translational modification affords an antibacterial siderophore-peptide conjugate
    Elizabeth M Nolan
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 129:14336-47. 2007

Collaborators

Detail Information

Publications29

  1. pmc Eating for two: how metabolism establishes interspecies interactions in the gut
    Michael A Fischbach
    Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA
    Cell Host Microbe 10:336-47. 2011
    ..We also discuss the metabolic considerations in maintaining the stability of host-associated microbial communities...
  2. pmc Antibiotics for emerging pathogens
    Michael A Fischbach
    Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Science 325:1089-93. 2009
    ....
  3. pmc Antibiotics from microbes: converging to kill
    Michael A Fischbach
    Department of Molecular Biology and Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Curr Opin Microbiol 12:520-7. 2009
    ....
  4. pmc Combination therapies for combating antimicrobial resistance
    Michael A Fischbach
    Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94158, USA
    Curr Opin Microbiol 14:519-23. 2011
    ..We will then consider examples of naturally occurring combination therapies produced by micro-organisms, and conclude by discussing key opportunities and challenges for making more widespread use of drug combinations...
  5. pmc The next frontier of systems biology: higher-order and interspecies interactions
    Michael A Fischbach
    Department of Bioengineering and Therapeutic Sciences and California Institute of Quantitative Biosciences, University of California, San Francisco, CA 94158, USA
    Genome Biol 11:208. 2010
    ..Systems approaches are not so different in essence from classical genetic and biochemical approaches, and in the future may become adopted so widely that the term 'systems biology' itself will become obsolete...
  6. pmc The identification of bacillaene, the product of the PksX megacomplex in Bacillus subtilis
    Rebecca A Butcher
    Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:1506-9. 2007
    ..Knowledge of bacillaene's structure has enabled us to annotate the pksX gene cluster and should facilitate the study of bacillaene's biosynthesis as well as its biological role in B. subtilis...
  7. pmc Directed evolution can rapidly improve the activity of chimeric assembly-line enzymes
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:11951-6. 2007
    ..Because functional restoration in these examples required only modest library sizes (10(3) to 10(4) clones) and three or fewer rounds of screening, our approach may be widely applicable even for NRPSs from genetically challenging hosts...
  8. pmc The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:16502-7. 2006
    ..Our findings indicate that the iroA gene cluster allows bacteria to evade this component of the innate immune system, rejuvenating their Ent-mediated iron-acquisition pathway and playing an important role in their virulence...
  9. ncbi request reprint Bromoenterobactins as potent inhibitors of a pathogen-associated, siderophore-modifying C-glycosyltransferase
    Hening Lin
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 128:9324-5. 2006
    ..This finding could lead to the discovery of effective antibiotics targeting iroA-containing bacteria...
  10. pmc Biosynthetic tailoring of microcin E492m: post-translational modification affords an antibacterial siderophore-peptide conjugate
    Elizabeth M Nolan
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 129:14336-47. 2007
    ..Nonenzymatic and base-catalyzed migration of the peptide to the C6' position affords the C6' glycosyl ester linkage observed in the mature toxin, MccE492m, isolated from bacterial cultures...
  11. pmc Thirteen posttranslational modifications convert a 14-residue peptide into the antibiotic thiocillin
    Laura C Wieland Brown
    Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA
    Proc Natl Acad Sci U S A 106:2549-53. 2009
    ..Remarkably, the C-terminal 14 residues of a 52-residue peptide precursor undergo 13 posttranslational modifications to give rise to thiocillin, making this antibiotic the most heavily posttranslationally-modified peptide known to date...
  12. pmc Dapdiamides, tripeptide antibiotics formed by unconventional amide ligases
    Jessica Dawlaty
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Nat Prod 73:441-6. 2010
    ..The dapdiamide family's promiscuous biosynthetic pathway contains two unconventional amide ligases that are predicted to couple its constituent monomers...
  13. doi request reprint A family of pyrazinone natural products from a conserved nonribosomal peptide synthetase in Staphylococcus aureus
    Michael Zimmermann
    Department of Bioengineering and Therapeutic Sciences, California Institute for Quantitative Biosciences, University of California, San Francisco, 94158, USA
    Chem Biol 17:925-30. 2010
    ..As an unexpected family of small molecule natural products from the pathogen S. aureus, the pyrazinones may open a new window into the interspecies interactions that underlie the poorly understood process of skin colonization...
  14. ncbi request reprint Localized protein interaction surfaces on the EntB carrier protein revealed by combinatorial mutagenesis and selection
    Jonathan R Lai
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Am Chem Soc 128:11002-3. 2006
    ..Therefore, designing noncognate carrier protein interactions in PKS and NRPS systems should be possible with very few mutations on a particular carrier protein...
  15. pmc A biosynthetic gene cluster for the acetyl-CoA carboxylase inhibitor andrimid
    Mi Jin
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Am Chem Soc 128:10660-1. 2006
    ..Therefore, future efforts can exploit the genetic manipulability of E. coli to engineer the andrimid synthase with the goal of producing a diverse set of andrimid analogues for clinical evaluation...
  16. ncbi request reprint New antibiotics from bacterial natural products
    Jon Clardy
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Biotechnol 24:1541-50. 2006
    ....
  17. pmc Natural products version 2.0: connecting genes to molecules
    Christopher T Walsh
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    J Am Chem Soc 132:2469-93. 2010
    ..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?..
  18. doi request reprint Total biosynthesis: in vitro reconstitution of polyketide and nonribosomal peptide pathways
    Elizabeth S Sattely
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave, Boston, MA 02115, USA
    Nat Prod Rep 25:757-93. 2008
    ..This review surveys efforts to reconstitute key steps in polyketide and nonribosomal peptide biosynthetic pathways with purified enzymes and substrates; 344 references are cited...
  19. pmc Inhibitors of sterol biosynthesis as Staphylococcus aureus antibiotics
    Christopher T Walsh
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Angew Chem Int Ed Engl 47:5700-2. 2008
  20. pmc A singular enzymatic megacomplex from Bacillus subtilis
    Paul D Straight
    Department of Microbiology and Molecular Genetics and Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:305-10. 2007
    ..Such an enzymatic megacomplex is unprecedented in bacterial subcellular organization and has important implications for engineering novel NRPS/PKSs...
  21. pmc The evolution of gene collectives: How natural selection drives chemical innovation
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:4601-8. 2008
    ..We discuss known examples to begin addressing two fundamental questions about the evolution of biosynthetic gene clusters: How do they propagate by horizontal transfer? How do they change to create new molecules?..
  22. pmc Production of α-galactosylceramide by a prominent member of the human gut microbiota
    Laura C Wieland Brown
    Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, California, United States of America
    PLoS Biol 11:e1001610. 2013
    ..Moreover, our data suggest that some Bacteroides sphingolipids might influence host immune homeostasis...
  23. pmc Structurally diverse natural products that cause potassium leakage trigger multicellularity in Bacillus subtilis
    Daniel Lopez
    Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 106:280-5. 2009
    ..We propose that KinC responds to lowered intracellular potassium concentration and that this is a quorum-sensing mechanism that enables B. subtilis to respond to related and unrelated bacteria...
  24. ncbi request reprint One pathway, many products
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 3:353-5. 2007
    ..Biosynthetic pathways for secondary metabolites usually make many products, not just one. In this Commentary, we consider why molecular promiscuity might be an evolutionarily advantageous feature of these pathways...
  25. ncbi request reprint Biochemistry. Directing biosynthesis
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Science 314:603-5. 2006
  26. ncbi request reprint Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Chem Rev 106:3468-96. 2006
  27. pmc A protein interaction surface in nonribosomal peptide synthesis mapped by combinatorial mutagenesis and selection
    Jonathan R Lai
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 103:5314-9. 2006
    ..These results suggest that helix 3 is a major recognition element in EntB-ArCP and demonstrate the utility of selection-based approaches for studying NRPS biosynthesis...
  28. pmc Trehalose biosynthesis promotes Pseudomonas aeruginosa pathogenicity in plants
    Slavica Djonovic
    Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, United States of America
    PLoS Pathog 9:e1003217. 2013
    ....
  29. ncbi request reprint How pathogenic bacteria evade mammalian sabotage in the battle for iron
    Michael A Fischbach
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Chem Biol 2:132-8. 2006
    ..The resulting modified forms of enterobactin, known as salmochelins, can evade siderocalin and are less hydrophobic than enterobactin, restoring this siderophore's iron-scavenging ability in mammals...