4-Nitrotryptophan is a substrate for the non-ribosomal peptide synthetase TxtB in the thaxtomin A biosynthetic pathway.
Thaxtomin A, a cyclic dipeptide with a nitrated tryptophan moiety, is a phytotoxic pathogenicity determinant in scab-causing Streptomyces species that inhibits cellulose synthesis by an unknown mechanism. Thaxtomin A is produced by the action of two non-ribosomal peptide synthetase modules (TxtA and TxtB) and a complement of modifying enzymes, although the order of biosynthesis has not yet been determined. Analysis of a thaxtomin dual module knockout mutant and single module knockout mutants revealed that 4-nitrotryptophan is an intermediate in thaxtomin A biosynthesis prior to backbone assembly. The 4-nitrotryptophan represents a novel substrate for non-ribosomal peptide synthetases. Through identification of N-methyl-4-nitrotryptophan in a single module knockout and the use of adenylation domain specificity prediction software, TxtB was identified as the non-ribosomal peptide synthetase module specific for 4-nitrotryptophan.
Johnson
Evan G
EG
Department of Plant Pathology and Plant-Microbe Biology, Cornell University, Ithaca, NY 14853, USA.
Krasnoff
Stuart B
SB
Bignell
Dawn R D
DR
Chung
Wen-Chuan
WC
Tao
Tao
T
Parry
Ronald J
RJ
Loria
Rosemary
R
Gibson
Donna M
DM
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism*; D012329:RNA, Bacterial / Q000235:genetics; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism
C500105:4-nitro-tryptophan; D001426:Bacterial Proteins; D007211:Indoles; D010879:Piperazines; D012329:RNA, Bacterial; C406691:thaxtomine A; D014364:Tryptophan; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase