Engineered biosynthesis of antiprotealide and other unnatural salinosporamide proteasome inhibitors.
A new shunt in the phenylalanine biosynthetic pathway to the nonproteinogenic amino acid L-3-cyclohex-2'-enylalanine was exploited in the marine bacterium Salinispora tropica by mutagenesis to allow for the genetic engineering of unnatural derivatives of the potent proteasome inhibitor salinosporamide A (2) such as antiprotealide (1).
Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92093, USA.
Ryan P
RP
McGlinchey
Markus
M
Nett
Alessandra S
AS
Eustáquio
Ratnakar N
RN
Asolkar
William
W
Fenical
Bradley S
BS
Moore
D007769:Lactams / Q000737:chemistry* / Q000378:metabolism*; D007783:Lactones / Q000737:chemistry* / Q000378:metabolism*; D008848:Micromonosporaceae / Q000235:genetics*; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry*; D015202:Protein Engineering; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism*
D007769:Lactams; D007783:Lactones; D011480:Protease Inhibitors; D011758:Pyrroles; C531354:antiprotealide; C475865:marizomib; D046988:Proteasome Endopeptidase Complex