Metabolites from the induced expression of cryptic single operons found in the genome of Burkholderia pseudomallei.
Bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. A subset of these cryptic genetic elements appears as individual operons. Here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium  Burkholderia pseudomallei . Placing these operons under the control of an inducible promoter led to the production of seven new metabolites. Among the molecules we identified are inhibitors of type-4 phosphodiesterases, suggesting that previously cryptic biosynthetic operons may encode metabolites that could contribute to microbial virulence by disrupting host signaling pathways.
Laboratory for Genetically Encoded Small Molecules, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, New York 10065, United States.
John B
JB
Biggins
Xiaofei
X
Liu
Zhiyang
Z
Feng
Sean F
SF
Brady
D016957:Burkholderia pseudomallei / Q000235:genetics* / Q000378:metabolism*; D015870:Gene Expression; D016680:Genome, Bacterial / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009876:Operon / Q000235:genetics*
Appl Environ Microbiol. 2008 May;74(10):2985-9
18310423
FEMS Microbiol Rev. 2009 Nov;33(6):1079-99
19732156
J Bacteriol. 2009 Jun;191(12):3909-18
19376863
Nat Chem Biol. 2009 Jul;5(7):450-2
19536102
BMC Microbiol. 2006 May 26;6:46
16725056
EMBO Mol Med. 2009 Jul;1(4):201-10
20049722
J Nat Prod. 2006 Apr;69(4):710-2
16643061
Chembiochem. 2009 Mar 2;10(4):625-33
19165837
Curr Opin Microbiol. 2006 Jun;9(3):252-60
16651020
Prog Med Chem. 2009;47:37-74
19328289
Org Lett. 2010 Feb 19;12(4):716-9
20095633
Br J Pharmacol. 2003 Nov;140(5):855-62
14585803
J Bacteriol. 2005 Jan;187(2):785-90
15629951
Nat Chem Biol. 2007 Sep;3(9):584-92
17704773
J Clin Microbiol. 2006 Dec;44(12):4601-4
17050819
BMC Genomics. 2005 Dec 07;6:174
16336651
Am Rev Respir Dis. 1985 Jun;131(6):923-7
3890643
J Antibiot (Tokyo). 1984 Jan;37(1):10-2
6321422
BMC Bioinformatics. 2009 Jun 16;10:185
19531248
Fungal Genet Biol. 2008 Mar;45(3):302-9
18029206
J Am Chem Soc. 2007 Oct 10;129(40):12102-3
17880089
Drug Discov Today. 2005 Nov 15;10(22):1503-19
16257373
Angew Chem Int Ed Engl. 2005 Oct 28;44(42):6828-46
16249991
Cell. 2006 Apr 21;125(2):237-46
16630813
Circ Res. 2007 Feb 16;100(3):309-27
17307970
Drug Discov Today. 2003 Dec 1;8(23):1078-84
14693467