An N-acyl homolog of mycothiol is produced in marine actinomycetes.
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-alpha-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.
Newton
Gerald L
GL
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA.
Jensen
Paul R
PR
Macmillan
John B
JB
Fenical
William
W
Fahey
Robert C
RC
D039903:Actinobacteria / Q000737:chemistry* / Q000201:enzymology / Q000302:isolation & purification; D000581:Amidohydrolases / Q000378:metabolism; D053898:Biosynthetic Pathways; D003545:Cysteine / Q000737:chemistry* / Q000302:isolation & purification*; D006020:Glycopeptides / Q000737:chemistry* / Q000302:isolation & purification*; D007294:Inositol / Q000737:chemistry* / Q000302:isolation & purification*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D014871:Water Microbiology
D006020:Glycopeptides; C089265:mycothiol; D007294:Inositol; D000581:Amidohydrolases; C413523:mycothiol S-conjugate amidase; D003545:Cysteine