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Scot Wolfe PhD

TitleProfessor
InstitutionUniversity of Massachusetts Medical School
DepartmentMolecular, Cell and Cancer Biology
AddressUniversity of Massachusetts Medical School
364 Plantation Street, LRB-619
Worcester MA 01605
Phone508-856-3953
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    Other Positions
    InstitutionUMMS - School of Medicine
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - School of Medicine
    DepartmentMolecular, Cell and Cancer Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBiochemistry and Molecular Pharmacology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentBioinformatics and Computational Biology

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentInterdisciplinary Graduate Program

    InstitutionUMMS - Graduate School of Biomedical Sciences
    DepartmentMD/PhD Program

    InstitutionUMMS - Programs, Centers and Institutes
    DepartmentBioinformatics and Integrative Biology

    InstitutionUMMS - Programs, Centers and Institutes
    DepartmentChemical Biology


    Collapse Biography 
    Collapse education and training
    California Institute of Technology, Pasadena, CA, United StatesBSChemistry & Biology
    Harvard University, Cambridge, MA, United StatesAMChemistry
    Harvard University, Cambridge, MA, United StatesPHDOrganic Chemistry

    Collapse Overview 
    Collapse overview


    Academic Background



    Scot Wolfe received his B.S. in Chemistry and Biology from Caltech in 1990, and his Ph.D. from Harvard in Chemistry in 1996. From 1996-2001 he was a post-doctoral fellow at Massachusetts Institute of Technology where his work was supported in part by the Leukemia and Lymphoma Society. In 2001, Dr. Wolfe joined the faculty of UMMS.



     



     



     



     



     






    Engineering precise gene editing systems for application in gene therapy and the analysis of gene regulatory networks



    Scot Wolfe My research program is focused on four inter-related areas (see our lab website for more details labs.umassmed.edu/WolfeLab):





    • Engineering programmable nucleases for the targeted cleavage of a single site within a vertebrate genome for gene therapy




    • Applying programmable nucleases to interrogate gene regulatory networks



    • Understanding fundamental aspects of protein-DNA recognition



     


    Creating more precise CRISPR/Cas9 nucleases for gene therapy - We are utilzing our expertise in protein engineering and protein-DNA recognition to create hybrid CRISPR/Cas9 nucleases to achieve single-site cleavage precision within the human genome.  Our new gene editing platforms provide dramatic improvements in specificity that make them promising tools to serve as the backbone for new cell-based therapeutics or gene therapy reagents. 


     


    Utilizing CRISPR/Cas9 to understand transcriptional regulatory networks in dendritic cells - We are collaborating with a team lead by Jeremy Luban (UMMS – PMM) and Manuel Garber (UMMS – BIB) to exploit recent technical advances in stem cell biology, reverse-genetic tools for primary human cells, and genome-wide assessment of transcripts, local chromatin features and long-range chromatin interactions to construct a model for the transcriptional regulatory network that underlies pathogen detection and maturation in human dendritic cells. We are utilizing CRISPR/Cas9 to modify transcription factors and regulatory elements that may underlie regulatory responses within these processes.  


     


    Utilizing CRISPR/Cas9 to inactivate latent HIV provirus in reservoir cells - We are collaborating with Jeremy Luban (UMMS – PMM) to lead a team that is investigating the chromatin architecture of latent HIV provirus in reservoir cells.  This data will be used to develop precise Cas9 nucleases and corresponding delivery systems to selectively inactivate provirus in reservoir cells to provide a path toward a functional cure for HIV.  


     


    Protein-DNA recognition - Our research on protein-DNA recognition is focused primarily on two of the most abundant families of DNA-binding domains in metazoans:




    Cys2His2 Zinc fingers & Homeodomains





    We have recently performed comprehensive analysis of homeodomain and Cys2His2 zinc finger specificities in D. melanogaster – (fruit fly) in collaboration with Michael Brodsky (UMMS-MCCB) & Gary Stormo (Wash. U). We have coupled this data with specificity data from artificial zinc fingers and homeodomains that we have selected using our bacterial one-hybrid system.  Using this information we can build simple qualitative models of recognition that allow the design of homeodomains with novel DNA-binding specificity.  This dataset can also be used to broadly predict the specificity of homeodomains (http://ural.wustl.edu/flyhd) and zinc fingers (http://stormo.wustl.edu/ZFModels/).  We continue to explore aspects of DNA recognition by these DNA-binding domain families to both more broadly and accurately predicting the specificity of naturally-occurring family members in all species and for rationally engineering the specificity of these DNA-binding domains.


     


    ZFNs/TALENs/Cas9 in Zebrafish - We are collaborating with Nathan Lawson (UMMS – MCCB) to develop new and improved tools for genome engineering in zebrafish.  We have used ZFNs, TALENs and Cas9 to make targeted knockouts of a number of genes of interest.  We are currently studying the function of miR-375 in pancreas development in the zebrafish to understand its function in the differentiation of alpha and beta cells of the endocrine pancreas.  


     


    B1H selection systems - We continue to develop a bacterial one-hybrid system for rapidly characterizing the DNA-binding specificities of sequence-specific transcription factors, both naturally-occurring and engineered. Using this technology have characterized >50% all of the sequence-specific transcription factors in the D. melanogaster genome (FlyFactorSurvey) in collaboration with the laboratory of Michael Brodsky (UMMS – MCCB). This dataset is being used to unravel transcription factor regulatory networks within the fly in collaboration with Saurabh Sinha (UI-Urbana Champaign). We have already begun building computational tools to allow the scientific community to identify cis-regulatory modules using clusters of phylogenetically conserved binding sites for these TFs in the fly genome that we have characterized to date (GenomeSurveyor -biotools.umassmed.edu/genomesurveyor).


     


     



     



     



     



     






     



     



     



     






    Collapse Rotation Projects


    Potential Rotation Projects



    Improving the Precision of CRISPR/Cas9 nucleases for gene therapy applications:



    We are working to improve the precision of the CRISPR/Cas9 system to generate nucleases that will cleave at only a single site in the genome.  These engineering efforts focus on increasing the DNA-binding precision of Cas9 and incorporating systems that will make cleavage drug-dependent.  These modified nucleases will then be applied to cell-culture systems for the targeted repair or inactivation of disease-causing alleles, or the inactivation of HIV proviral genomes.



     










    Creation of CRISPR/Cas9-based tools for zebrafish:



    We are developing CRISPR/Cas9 systems for spatial and temporally restricted editing or gene regulation in zebrafish.  These tools will be used to determine the tissue- or cell-type specific function of target genes during development. 










    End of Rotation Projects




     






     






     






     






     




    Collapse Bibliographic 
    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
    List All   |   Timeline
    1. Zhu LJ, Lawrence M, Gupta A, Pagès H, Kucukural A, Garber M, Wolfe SA. GUIDEseq: a bioconductor package to analyze GUIDE-Seq datasets for CRISPR-Cas nucleases. BMC Genomics. 2017 May 15; 18(1):379. PMID: 28506212.
      View in: PubMed
    2. Markert MJ, Zhang Y, Enuameh MS, Reppert SM, Wolfe SA, Merlin C. Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis. G3 (Bethesda). 2016 Apr 07; 6(4):905-15. PMID: 26837953.
      View in: PubMed
    3. Brunner D, Burke W, Kuang AQ, LaBombard B, Lipschultz B, Wolfe S. Feedback system for divertor impurity seeding based on real-time measurements of surface heat flux in the Alcator C-Mod tokamak. Rev Sci Instrum. 2016 Feb; 87(2):023504. PMID: 26931846.
      View in: PubMed
    4. Yin H, Song CQ, Dorkin JR, Zhu LJ, Li Y, Wu Q, Park A, Yang J, Suresh S, Bizhanova A, Gupta A, Bolukbasi MF, Walsh S, Bogorad RL, Gao G, Weng Z, Dong Y, Koteliansky V, Wolfe SA, Langer R, Xue W, Anderson DG. Therapeutic genome editing by combined viral and non-viral delivery of CRISPR system components in vivo. Nat Biotechnol. 2016 Mar; 34(3):328-33. PMID: 26829318.
      View in: PubMed
    5. Bolukbasi MF, Gupta A, Wolfe SA. Creating and evaluating accurate CRISPR-Cas9 scalpels for genomic surgery. Nat Methods. 2016 Jan; 13(1):41-50. PMID: 26716561.
      View in: PubMed
    6. Wang JP, Rancy SK, Lee SK, Feinberg JH, Wolfe SW. Shoulder and Elbow Recovery at 2 and 11 Years Following Brachial Plexus Reconstruction. J Hand Surg Am. 2016 Feb; 41(2):173-9. PMID: 26718077.
      View in: PubMed
    7. Sontheimer EJ, Wolfe SA. Cas9 gets a classmate. Nat Biotechnol. 2015 Dec 09; 33(12):1240-1241. PMID: 26650011.
      View in: PubMed
    8. Bolukbasi MF, Gupta A, Oikemus S, Derr AG, Garber M, Brodsky MH, Zhu LJ, Wolfe SA. DNA-binding-domain fusions enhance the targeting range and precision of Cas9. Nat Methods. 2015 Dec; 12(12):1150-6. PMID: 26480473.
      View in: PubMed
    9. Dy CJ, Lee SK, Mancuso CA, Wolfe SW. In Reply. J Hand Surg Am. 2015 Jul; 40(7):1504-5. PMID: 26095057.
      View in: PubMed
    10. Blatti C, Kazemian M, Wolfe S, Brodsky M, Sinha S. Integrating motif, DNA accessibility and gene expression data to build regulatory maps in an organism. Nucleic Acids Res. 2015 Apr 30; 43(8):3998-4012. PMID: 25791631.
      View in: PubMed
    11. Ma H, Naseri A, Reyes-Gutierrez P, Wolfe SA, Zhang S, Pederson T. Multicolor CRISPR labeling of chromosomal loci in human cells. Proc Natl Acad Sci U S A. 2015 Mar 10; 112(10):3002-7. PMID: 25713381.
      View in: PubMed
    12. Wang JP, Rancy SK, DiCarlo EF, Wolfe SW. Recurrent pigmented villonodular synovitis and multifocal giant cell tumor of the tendon sheath: case report. J Hand Surg Am. 2015 Mar; 40(3):537-41. PMID: 25577961.
      View in: PubMed
    13. Kok FO, Shin M, Ni CW, Gupta A, Grosse AS, van Impel A, Kirchmaier BC, Peterson-Maduro J, Kourkoulis G, Male I, DeSantis DF, Sheppard-Tindell S, Ebarasi L, Betsholtz C, Schulte-Merker S, Wolfe SA, Lawson ND. Reverse genetic screening reveals poor correlation between morpholino-induced and mutant phenotypes in zebrafish. Dev Cell. 2015 Jan 12; 32(1):97-108. PMID: 25533206.
      View in: PubMed
    14. Dy CJ, Garg R, Lee SK, Tow P, Mancuso CA, Wolfe SW. A systematic review of outcomes reporting for brachial plexus reconstruction. J Hand Surg Am. 2015 Feb; 40(2):308-13. PMID: 25510158.
      View in: PubMed
    15. Weicksel SE, Gupta A, Zannino DA, Wolfe SA, Sagerström CG. Targeted germ line disruptions reveal general and species-specific roles for paralog group 1 hox genes in zebrafish. BMC Dev Biol. 2014 Jun 05; 14:25. PMID: 24902847.
      View in: PubMed
    16. Gupta A, Christensen RG, Bell HA, Goodwin M, Patel RY, Pandey M, Enuameh MS, Rayla AL, Zhu C, Thibodeau-Beganny S, Brodsky MH, Joung JK, Wolfe SA, Stormo GD. An improved predictive recognition model for Cys(2)-His(2) zinc finger proteins. Nucleic Acids Res. 2014 Apr; 42(8):4800-12. PMID: 24523353.
      View in: PubMed
    17. Kok FO, Gupta A, Lawson ND, Wolfe SA. Construction and application of site-specific artificial nucleases for targeted gene editing. Methods Mol Biol. 2014; 1101:267-303. PMID: 24233786.
      View in: PubMed
    18. Kearns NA, Genga RM, Enuameh MS, Garber M, Wolfe SA, Maehr R. Cas9 effector-mediated regulation of transcription and differentiation in human pluripotent stem cells. Development. 2014 Jan; 141(1):219-23. PMID: 24346702.
      View in: PubMed
    19. Cheng Q, Kazemian M, Pham H, Blatti C, Celniker SE, Wolfe SA, Brodsky MH, Sinha S. Computational identification of diverse mechanisms underlying transcription factor-DNA occupancy. PLoS Genet. 2013; 9(8):e1003571. PMID: 23935523.
      View in: PubMed
    20. Kazemian M, Pham H, Wolfe SA, Brodsky MH, Sinha S. Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development. Nucleic Acids Res. 2013 Sep; 41(17):8237-52. PMID: 23847101.
      View in: PubMed
    21. Gupta A, Hall VL, Kok FO, Shin M, McNulty JC, Lawson ND, Wolfe SA. Targeted chromosomal deletions and inversions in zebrafish. Genome Res. 2013 Jun; 23(6):1008-17. PMID: 23478401.
      View in: PubMed
    22. Enuameh MS, Asriyan Y, Richards A, Christensen RG, Hall VL, Kazemian M, Zhu C, Pham H, Cheng Q, Blatti C, Brasefield JA, Basciotta MD, Ou J, McNulty JC, Zhu LJ, Celniker SE, Sinha S, Stormo GD, Brodsky MH, Wolfe SA. Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants. Genome Res. 2013 Jun; 23(6):928-40. PMID: 23471540.
      View in: PubMed
    23. Zhu C, Gupta A, Hall VL, Rayla AL, Christensen RG, Dake B, Lakshmanan A, Kuperwasser C, Stormo GD, Wolfe SA. Using defined finger-finger interfaces as units of assembly for constructing zinc-finger nucleases. Nucleic Acids Res. 2013 Feb 1; 41(4):2455-65. PMID: 23303772.
      View in: PubMed
    24. Merlin C, Beaver LE, Taylor OR, Wolfe SA, Reppert SM. Efficient targeted mutagenesis in the monarch butterfly using zinc-finger nucleases. Genome Res. 2013 Jan; 23(1):159-68. PMID: 23009861.
      View in: PubMed
    25. Anderson DM, George R, Noyes MB, Rowton M, Liu W, Jiang R, Wolfe SA, Wilson-Rawls J, Rawls A. Characterization of the DNA-binding properties of the Mohawk homeobox transcription factor. J Biol Chem. 2012 Oct 12; 287(42):35351-9. PMID: 22923612.
      View in: PubMed
    26. Shin J, Padmanabhan A, de Groh ED, Lee JS, Haidar S, Dahlberg S, Guo F, He S, Wolman MA, Granato M, Lawson ND, Wolfe SA, Kim SH, Solnica-Krezel L, Kanki JP, Ligon KL, Epstein JA, Look AT. Zebrafish neurofibromatosis type 1 genes have redundant functions in tumorigenesis and embryonic development. Dis Model Mech. 2012 Nov; 5(6):881-94. PMID: 22773753.
      View in: PubMed
    27. Christensen RG, Enuameh MS, Noyes MB, Brodsky MH, Wolfe SA, Stormo GD. Recognition models to predict DNA-binding specificities of homeodomain proteins. Bioinformatics. 2012 Jun 15; 28(12):i84-9. PMID: 22689783.
      View in: PubMed
    28. Gupta A, Christensen RG, Rayla AL, Lakshmanan A, Stormo GD, Wolfe SA. An optimized two-finger archive for ZFN-mediated gene targeting. Nat Methods. 2012 Jun; 9(6):588-90. PMID: 22543349.
      View in: PubMed
    29. Chu SW, Noyes MB, Christensen RG, Pierce BG, Zhu LJ, Weng Z, Stormo GD, Wolfe SA. Exploring the DNA-recognition potential of homeodomains. Genome Res. 2012 Oct; 22(10):1889-98. PMID: 22539651.
      View in: PubMed
    30. Zhu C, Smith T, McNulty J, Rayla AL, Lakshmanan A, Siekmann AF, Buffardi M, Meng X, Shin J, Padmanabhan A, Cifuentes D, Giraldez AJ, Look AT, Epstein JA, Lawson ND, Wolfe SA. Evaluation and application of modularly assembled zinc-finger nucleases in zebrafish. Development. 2011 Oct; 138(20):4555-64. PMID: 21937602.
      View in: PubMed
    31. Lawson ND, Wolfe SA. Forward and reverse genetic approaches for the analysis of vertebrate development in the zebrafish. Dev Cell. 2011 Jul 19; 21(1):48-64. PMID: 21763608.
      View in: PubMed
    32. Christensen RG, Gupta A, Zuo Z, Schriefer LA, Wolfe SA, Stormo GD. A modified bacterial one-hybrid system yields improved quantitative models of transcription factor specificity. Nucleic Acids Res. 2011 Jul; 39(12):e83. PMID: 21507886.
      View in: PubMed
    33. Bussmann J, Wolfe SA, Siekmann AF. Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling. Development. 2011 May; 138(9):1717-26. PMID: 21429983.
      View in: PubMed
    34. Zhu LJ, Christensen RG, Kazemian M, Hull CJ, Enuameh MS, Basciotta MD, Brasefield JA, Zhu C, Asriyan Y, Lapointe DS, Sinha S, Wolfe SA, Brodsky MH. FlyFactorSurvey: a database of Drosophila transcription factor binding specificities determined using the bacterial one-hybrid system. Nucleic Acids Res. 2011 Jan; 39(Database issue):D111-7. PMID: 21097781.
      View in: PubMed
    35. Gupta A, Meng X, Zhu LJ, Lawson ND, Wolfe SA. Zinc finger protein-dependent and -independent contributions to the in vivo off-target activity of zinc finger nucleases. Nucleic Acids Res. 2011 Jan; 39(1):381-92. PMID: 20843781.
      View in: PubMed
    36. Kazemian M, Blatti C, Richards A, McCutchan M, Wakabayashi-Ito N, Hammonds AS, Celniker SE, Kumar S, Wolfe SA, Brodsky MH, Sinha S. Quantitative analysis of the Drosophila segmentation regulatory network using pattern generating potentials. PLoS Biol. 2010 Aug 17; 8(8). PMID: 20808951.
      View in: PubMed
    37. Cifuentes D, Xue H, Taylor DW, Patnode H, Mishima Y, Cheloufi S, Ma E, Mane S, Hannon GJ, Lawson ND, Wolfe SA, Giraldez AJ. A novel miRNA processing pathway independent of Dicer requires Argonaute2 catalytic activity. Science. 2010 Jun 25; 328(5986):1694-8. PMID: 20448148.
      View in: PubMed
    38. Siekmann AF, Standley C, Fogarty KE, Wolfe SA, Lawson ND. Chemokine signaling guides regional patterning of the first embryonic artery. Genes Dev. 2009 Oct 1; 23(19):2272-7. PMID: 19797767.
      View in: PubMed
    39. Ince-Cushman A, Rice JE, Reinke M, Greenwald M, Wallace G, Parker R, Fiore C, Hughes JW, Bonoli P, Shiraiwa S, Hubbard A, Wolfe S, Hutchinson IH, Marmar E, Bitter M, Wilson J, Hill K. Observation of self-generated flows in tokamak plasmas with lower-hybrid-driven current. Phys Rev Lett. 2009 Jan 23; 102(3):035002. PMID: 19257362.
      View in: PubMed
    40. Marx RG, Fives G, Chu SK, Daluiski A, Wolfe SW. Allograft reconstruction for symptomatic chronic complete proximal hamstring tendon avulsion. Knee Surg Sports Traumatol Arthrosc. 2009 Jan; 17(1):19-23. PMID: 18682918.
      View in: PubMed
    41. Noyes MB, Christensen RG, Wakabayashi A, Stormo GD, Brodsky MH, Wolfe SA. Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites. Cell. 2008 Jun 27; 133(7):1277-89. PMID: 18585360.
      View in: PubMed
    42. Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA. Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol. 2008 Jun; 26(6):695-701. PMID: 18500337.
      View in: PubMed
    43. Noyes MB, Meng X, Wakabayashi A, Sinha S, Brodsky MH, Wolfe SA. A systematic characterization of factors that regulate Drosophila segmentation via a bacterial one-hybrid system. Nucleic Acids Res. 2008 May; 36(8):2547-60. PMID: 18332042.
      View in: PubMed
    44. Meng X, Thibodeau-Beganny S, Jiang T, Joung JK, Wolfe SA. Profiling the DNA-binding specificities of engineered Cys2His2 zinc finger domains using a rapid cell-based method. Nucleic Acids Res. 2007; 35(11):e81. PMID: 17537811.
      View in: PubMed
    45. Meng X, Smith RM, Giesecke AV, Joung JK, Wolfe SA. Counter-selectable marker for bacterial-based interaction trap systems. Biotechniques. 2006 Feb; 40(2):179-84. PMID: 16526407.
      View in: PubMed
    46. Meng X, Wolfe SA. Identifying DNA sequences recognized by a transcription factor using a bacterial one-hybrid system. Nat Protoc. 2006; 1(1):30-45. PMID: 17406209.
      View in: PubMed
    47. Meng X, Brodsky MH, Wolfe SA. A bacterial one-hybrid system for determining the DNA-binding specificity of transcription factors. Nat Biotechnol. 2005 Aug; 23(8):988-94. PMID: 16041365.
      View in: PubMed
    48. Wolfe SA. Mapping key elements of a protein motif. Chem Biol. 2004 Jul; 11(7):889-91. PMID: 15271344.
      View in: PubMed
    49. Wolfe SA, Grant RA, Pabo CO. Structure of a designed dimeric zinc finger protein bound to DNA. Biochemistry. 2003 Nov 25; 42(46):13401-9. PMID: 14621985.
      View in: PubMed
    50. Fernández MJ, Adrio JL, Piret JM, Wolfe S, Ro S, Demain AL. Stimulatory effect of growth in the presence of alcohols on biotransformation of penicillin G into cephalosporin-type antibiotics by resting cells of Streptomyces clavuligerus NP1. Appl Microbiol Biotechnol. 1999 Oct; 52(4):484-8. PMID: 10570794.
      View in: PubMed
    51. Cho H, Adrio JL, Luengo JM, Wolfe S, Ocran S, Hintermann G, Piret JM, Demain AL. Elucidation of conditions allowing conversion of penicillin G and other penicillins to deacetoxycephalosporins by resting cells and extracts of Streptomyces clavuligerus NP1. Proc Natl Acad Sci U S A. 1998 Sep 29; 95(20):11544-8. PMID: 9751702.
      View in: PubMed
    52. Wolfe SW, Gupta A, Crisco JJ. Kinematics of the scaphoid shift test. J Hand Surg Am. 1997 Sep; 22(5):801-6. PMID: 9330136.
      View in: PubMed
    53. Zhang J, Wolfe S, Demain AL. Biochemical studies on the activity of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase from Streptomyces clavuligerus. Biochem J. 1992 May 1; 283 ( Pt 3):691-8. PMID: 1590759.
      View in: PubMed
    54. Xiao XF, Wolfe S, Demain AL. Purification and characterization of cephalosporin 7 alpha-hydroxylase from Streptomyces clavuligerus. Biochem J. 1991 Dec 1; 280 ( Pt 2):471-4. PMID: 1747122.
      View in: PubMed
    55. Owen TA, Holthuis J, Markose E, van Wijnen AJ, Wolfe SA, Grimes SR, Lian JB, Stein GS. Modifications of protein-DNA interactions in the proximal promoter of a cell-growth-regulated histone gene during onset and progression of osteoblast differentiation. Proc Natl Acad Sci U S A. 1990 Jul; 87(13):5129-33. PMID: 2367528.
      View in: PubMed
    56. Jhang J, Wolfe S, Demain AL. Phosphate regulation of ACV synthetase and cephalosporin biosynthesis in Streptomyces clavuligerus. FEMS Microbiol Lett. 1989 Jan 15; 48(2):145-50. PMID: 2721913.
      View in: PubMed
    57. Zhang JY, Wolfe S, Demain AL. Effect of ammonium as nitrogen source on production of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase by Cephalosporium acremonium C-10. J Antibiot (Tokyo). 1987 Dec; 40(12):1746-50. PMID: 3429339.
      View in: PubMed
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