Factors affecting the normal and branched-chain acyl moieties of teicoplanin components produced by Actinoplanes teichomyceticus

Abstract

Teicoplanin, a glycopeptide antibiotic produced by Actinopfanes teichornyceticus, comprises five main components, denoted T-A2-1 to T-A2-5, differing in the structure of their acyl side chain, which is linear in T-A2-1 and T-A2-3 and branched in the other components. Production of T-A2-1, characterized by a linear C1O:l acyl moiety, is entirely dependent on the presence of linoleate in the fermentation medium. Addition to the medium of oleic acid esters at 2 g 1-l increases the yields of T-A2-3, characterized by a linear C1O:O acyl chain, about threefold. The antibiotic linear side chains thus appear to originate from C18 unsaturated acid by P-oxidation degradation. The percentage of T-A2-2, T-A2-4 and T-A2-5, bearing the iso-ClO:O, anteiso-Cll :O and iso-Cl1 :O acyl moieties, respectively, is strongly influenced by the presence in the medium of the amino acids known to be precursors of branched-chain fatty acids. Thus, valine increases the production of T-A2-2 whereas isoleucine or leucine increase the relative yields of T-A2-4 or T-A2-5, respectively. Analysis of the total cell lipids upon addition of the same amino acid shows corresponding increases in the proportion of the iso-Cl6 : 0, iso-Cl5 : 0 or anteiso-C17 : 0. A mutant A. teichornyceticus strain, which produces a novel teicoplanin with a linear 0 : 0 chain, differs from the wild strain in the presence of the linear C17: 1 acid in its lipids. The relative incorporation of [14C]acetate into teicoplanin acyl moieties is substantially lower when this precursor is added to grown A. teichornyceticus mycelium rather than at the time of inoculation. The results suggest that teicoplanin branched acyl moieties also originate from P-oxidation degradation of cellular long-chain fatty acids.

Production of teicoplanin by valine analogue-resistant mutant strains of Actinoplanes teichomyceticus

“…L-valine is the precursor of the acyl moiety of teicoplanin A 2-2 , which is the main component in the antibiotic (Assi et al 1986;Borghi et al 1991;Wang et al 1996). A. teichomyceticus 97-5-74 is susceptible to DL-VH, the L-valine analogue.…”

“…L-valine is the biosynthetic precursor of the fatty acid moieties of teicoplanin A 2-2 . The biosynthesis of teicoplanin in A. teichomyceticus is profoundly influenced by the addition of L-valine to the culture medium: L-valine-directed biosynthesis leads to teicoplanin A 2-2 production and an increased total teicoplanin in titer (Assi et al 1986;Borghi et al 1991;Wang et al 1996).…”

Factors influencing cell fatty acid composition and A40926 antibiotic complex production in Nonomuraea sp. ATCC 39727

“…Main components of the complex are A 0 (R1 = iso-C11:0), A 1 (R1 = n-C11:0), B 0 (R1 = iso-C12:0) and B 1 (R1 = n-C12:0). The origin of the fatty acids constituting the acyl moieties of the glycopeptide molecules has been previously studied in the structurally closely related teicoplanin [2], A40926 [20] and in the lipopeptide antibiotic ramoplanin [3]. Borghi et al [2] studied factors aVecting the normal and branched-chain acyl moieties of teicoplanin, and demostrated that teicoplanin acyl moieties are biosynthesized from longer cell fatty acids by shortening of the carbon chains.…”

“…The origin of the fatty acids constituting the acyl moieties of the glycopeptide molecules has been previously studied in the structurally closely related teicoplanin [2], A40926 [20] and in the lipopeptide antibiotic ramoplanin [3]. Borghi et al [2] studied factors aVecting the normal and branched-chain acyl moieties of teicoplanin, and demostrated that teicoplanin acyl moieties are biosynthesized from longer cell fatty acids by shortening of the carbon chains. Since apparently the shortening is performed by the classical -oxidation mechanism by loss of acetic acid units starting from the carboxyl end, the characteristic end terminal features (branched or linear) are conserved.…”

Production of Teicoplanin fromActinoplanes teichomyceticusID9303 by Adding Proline

“…The productivity and ratio of teicoplanin were affected by the addition of amino acids at various concentrations to the media. 5,6) An influence of leucine and valine on ramoplanin (a kind of glycopeptide antibiotic) production has been reported. 7) Judging by these results, it appeared that amino acids acted as a precursor or stimulator in the production of teicoplanin.…”