TY - JOUR
T1 - An N-acyl homolog of mycothiol is produced in marine actinomycetes
AU - Newton, Gerald L.
AU - Jensen, Paul R.
AU - MacMillan, John B.
AU - Fenical, William
AU - Fahey, Robert C.
N1 - Funding Information:
Acknowledgments This work was supported by NIH grant AI49174 from the National Institute of Allergy and Infectious Diseases and grant MCB-0235705 from the National Science Foundation to RCF. Additional support was provided from the NIH, National Cancer Institute, under grant CA-44848 (to WF), and in part by the National Sea Grant College Program of the US Department of Commerce’s National Oceanic and Atmospheric Administration under NOAA Grant # NA040AR4170038, project # R/MP-96, through the California Sea Grant College Program; and in part by the California State Resources Agency to WF. The views expressed herein do not necessarily reXect the views of any of those organizations. We thank Nancy Buchmeier for critical review of the manuscript.
PY - 2008/11
Y1 - 2008/11
N2 - Marine actinomycetes have generated much recent interest as a potentially valuable source of novel antibiotics. Like terrestrial actinomycetes the marine actinomycetes are shown here to produce mycothiol as their protective thiol. However, a novel thiol, U25, was produced by MAR2 strain CNQ703 upon progression into stationary phase when secondary metabolite production occurred and became the dominant thiol. MSH and U25 were maintained in a reduced state during early stationary phase, but become significantly oxidized after 10 days in culture. Isolation and structural analysis of the monobromobimane derivative identified U25 as a homolog of mycothiol in which the acetyl group attached to the nitrogen of cysteine is replaced by a propionyl residue. This N-propionyl-desacetyl- mycothiol was present in 13 of the 17 strains of marine actinomycetes examined, including five strains of Salinispora and representatives of the MAR2, MAR3, MAR4 and MAR6 groups. Mycothiol and its precursor, the pseudodisaccharide 1-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol, were found in all strains. High levels of mycothiol S-conjugate amidase activity, a key enzyme in mycothiol-dependent detoxification, were found in most strains. The results demonstrate that major thiol/disulfide changes accompany secondary metabolite production and suggest that mycothiol-dependent detoxification is important at this developmental stage.
AB - Marine actinomycetes have generated much recent interest as a potentially valuable source of novel antibiotics. Like terrestrial actinomycetes the marine actinomycetes are shown here to produce mycothiol as their protective thiol. However, a novel thiol, U25, was produced by MAR2 strain CNQ703 upon progression into stationary phase when secondary metabolite production occurred and became the dominant thiol. MSH and U25 were maintained in a reduced state during early stationary phase, but become significantly oxidized after 10 days in culture. Isolation and structural analysis of the monobromobimane derivative identified U25 as a homolog of mycothiol in which the acetyl group attached to the nitrogen of cysteine is replaced by a propionyl residue. This N-propionyl-desacetyl- mycothiol was present in 13 of the 17 strains of marine actinomycetes examined, including five strains of Salinispora and representatives of the MAR2, MAR3, MAR4 and MAR6 groups. Mycothiol and its precursor, the pseudodisaccharide 1-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol, were found in all strains. High levels of mycothiol S-conjugate amidase activity, a key enzyme in mycothiol-dependent detoxification, were found in most strains. The results demonstrate that major thiol/disulfide changes accompany secondary metabolite production and suggest that mycothiol-dependent detoxification is important at this developmental stage.
KW - Marine actinomycetes
KW - Mca
KW - Mycothiol
KW - N-propionyl-desacetyl-mycothiol
KW - Salinispora arencola
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U2 - 10.1007/s00203-008-0405-3
DO - 10.1007/s00203-008-0405-3
M3 - Article
C2 - 18629474
AN - SCOPUS:55449105798
SN - 0302-8933
VL - 190
SP - 547
EP - 557
JO - Archives of Microbiology
JF - Archives of Microbiology
IS - 5
ER -