40997-92-0Relevant articles and documents
Mapping the sirodesmin PL biosynthetic pathway- A remarkable intrinsic steric deuterium isotope effect on a 1H NMR chemical shift determines β-proton exchange in tyrosine
Pedras, M. Soledade C.,Yu, Yang
supporting information; experimental part, p. 556 - 562 (2009/10/17)
Sirodesmin PL is both an antibiotic and a phytotoxin produced by a fungal plant pathogen (Leptosphaeria maculans,asexual stage Phoma lingam) that causes blackleg disease on crucifers. To determine potential biosynthetic precursors of sirodesmin PL, deuterated compounds were synthesized and incubated with cultures of L. maculans. Incorporations of deuterium into sirodesmin PL (7) and its precursor phomamide (4) were determined using 1H and 13C NMR spectroscopy, LCHRMS-ESI and HRMS-EI spectrometry. Spectroscopic analyses established that [3,3-2H2]L- tyrosine (1a), [3,3-2H2]O-prenyl-L-tyrosine (9a), [3,3,5',5',5'-2H5]O-prenyl-L-tyrosine (9b), and [5,5- 2H2]phomamide (4a) were incorporated efficiently into sirodesmin PL (7). Interestingly, an unexpected "twist" revealed that one of the β-deuteria (pro-R) of [3,3-2H2]L-tyrosine (1a) was exchanged stereospecifically before incorporation into sirodesmin PL (7). As well, our studies revealed that O-prenyl-Ltyrosine is likely to be the first committed precursor en route to sirodesmin PL (7).
Structure-Activity Studies with the αβ-Dihydroxyacid Dehydratase of Salmonella typhimurium
Armstrong, Frank B.,Lipscomb, Elizabeth L.,Crout, David H. G.,Morgan, Phillip J.
, p. 691 - 696 (2007/10/02)
(2RS,3RS)- and (2RS,3SR)-2,3-Dihydroxybutanoic acids, (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid, (2RS)-2-ethyl-2,3-dihydroxypentanoic acid, (2RS,3RS)- and (2RS,3SR)-2,3-dihydroxy-3-methylhexanoic acids, and (2RS,3RS)- and (2RS,3SR)-2,3-dihydroxy-3-methylheptanoic acids were synthesised.These acids, as well as (RS)-2,3-dihydroxy-3-methylbutanoic acid and (RS)-glyceric acid were tested as substrates for the αβ-dihydroxyacid dehydratase of the isoleucine-valine biosynthetic pathway of Salmonella typhimurium.For acids having a propyl group at C-3, the activities were greatly reduced compared with those obtained for the natural substrates (2R,3R)-2,3-dihydroxy-3-methylpentanoic acid and (R)-2,3-dihydroxy-3-methylbutanoic acid .For acids having an n-butyl substituent at C-3, the activities were close to zero. (2RS,3SR)-2,3-Dihydroxybutanoic acid (threo isomer) underwent dehydration at a rate comparable with that of (2R,3R)-DHI, the natural substrate in the isoleucine pathway, whereas the (2RS,3RS)-acid (erythro-isomer) had much lower activity and (RS)-glyceric acid had even less activity.These results illustrate differences in the alkyl group requirements with respect to the areas of the binding site of the enzyme that accomodate the C-3 substituents.They also demonstrate the size limits of the alkyl groups that can be accomodated in substrate analogues.
