title: Arimetamycin A: improving clinically relevant families of natural products through sequence-guided screening of soil metagenomes.
abstract: Sequence-tag-guided screening of soil environmental DNA libraries can be used to guide the discovery of new compounds with improved properties. In heterologous expression experiments the eDNA-derived arm cluster encodes arimetamycin A, an anthracycline that is more potent than clinically used natural anthracyclines and retains activity against multidrug-resistant (MDR) cancer cells.
authors.affiliation: Laboratory of Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10065 (USA) http://lab.rockefeller.edu/brady/
authors.forename: Hahk-Soo
authors.initials: HS
authors.lastname: Kang
authors.forename: Sean F
authors.initials: SF
authors.lastname: Brady
mesh_terms: D018943:Anthracyclines / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D054892:Metagenome; D064307:Microbiota / Q000235:genetics*; D012988:Soil Microbiology; D013329:Structure-Activity Relationship
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001688:Biological Products; D004269:DNA, Bacterial
keywords: MDR; anthracyclines; antitumor agents; metagenomics; natural products
references.citation: Nat Protoc. 2007;2(5):1297-305
references.pmid: 17546026
references.citation: Appl Environ Microbiol. 2012 May;78(10):3744-52
references.pmid: 22427492
references.citation: Chembiochem. 2008 Mar 3;9(4):624-33
references.pmid: 18224649
references.citation: Curr Opin Biotechnol. 2004 Jun;15(3):199-204
references.pmid: 15193327
references.citation: Cancer Chemother Pharmacol. 1993;31(4):301-7
references.pmid: 8422694
references.citation: Curr Opin Microbiol. 2002 Jun;5(3):240-5
references.pmid: 12057676
references.citation: Biochem Pharmacol. 2001 Apr 15;61(8):933-8
references.pmid: 11286984
references.citation: FASEB J. 1998 Mar;12(3):265-74
references.pmid: 9506471
references.citation: J Antibiot (Tokyo). 1981 Dec;34(12):1596-607
references.pmid: 6949896
references.citation: Mol Biosyst. 2010 Jul;6(7):1180-5
references.pmid: 20473441
references.citation: Appl Environ Microbiol. 2006 Jun;72(6):4172-83
references.pmid: 16751529
references.citation: Mol Genet Genomics. 2001 Oct;266(2):276-88
references.pmid: 11683270
references.citation: Nat Chem Biol. 2009 Jul;5(7):494-501
references.pmid: 19448639
references.citation: Int J Oncol. 1993 Apr;2(4):677-81
references.pmid: 21573611
references.citation: Angew Chem Int Ed Engl. 2009;48(34):6257-61
references.pmid: 19621341
references.citation: Nat Prod Rep. 2007 Feb;24(1):162-90
references.pmid: 17268612
references.citation: Methods Enzymol. 2009;459:339-65
references.pmid: 19362647
references.citation: Appl Environ Microbiol. 2004 Sep;70(9):5522-7
references.pmid: 15345440
references.citation: Org Biomol Chem. 2009 May 7;7(9):1753-60
references.pmid: 19590766
references.citation: Eur J Med Chem. 2001 Jun;36(6):483-93
references.pmid: 11525839
references.citation: Appl Environ Microbiol. 2003 Jan;69(1):49-55
references.pmid: 12513976
references.citation: J Mol Microbiol Biotechnol. 2000 Jul;2(3):271-6
references.pmid: 10937435
references.citation: J Bacteriol. 1997 Dec;179(23):7360-8
references.pmid: 9393700
references.citation: Angew Chem Int Ed Engl. 2009;48(26):4688-716
references.pmid: 19514004
references.citation: Pharmacol Rev. 2004 Jun;56(2):185-229
references.pmid: 15169927
references.citation: J Med Chem. 2006 Feb 9;49(3):932-41
references.pmid: 16451059
references.citation: Proc Natl Acad Sci U S A. 2008 Mar 25;105(12):4595-600
references.pmid: 18250311
references.citation: Mol Pharmacol. 1994 May;45(5):908-15
references.pmid: 8190107
references.citation: Drug Discov Today. 2000 Jul;5(7):294-300
references.pmid: 10856912
references.citation: Appl Environ Microbiol. 1996 Feb;62(2):316-22
references.pmid: 8593035
references.citation: Chem Biol. 1998 Oct;5(10):R245-9
references.pmid: 9818143
references.citation: Cancer Res. 1987 May 15;47(10):2594-8
references.pmid: 2436751
references.citation: Curr Opin Chem Biol. 2012 Apr;16(1-2):109-16
references.pmid: 22455793
references.citation: J Microbiol Methods. 2005 Jul;62(1):1-11
references.pmid: 15823390
references.citation: J Biol Chem. 2005 Apr 1;280(13):13055-61
references.pmid: 15632111
references.citation: Gene. 1994 Dec 30;151(1-2):1-10
references.pmid: 7828855
references.citation: Cancer Chemother Pharmacol. 1986;18(3):185-97
references.pmid: 2948729
references.citation: Annu Rev Microbiol. 2003;57:369-94
references.pmid: 14527284
references.citation: Appl Microbiol Biotechnol. 2007 Jul;75(5):955-62
references.pmid: 17396253