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The lipopeptide antibiotic complex, A21978 C, is produced by Streptomyces roseosporus in liquid shake culture. The major antibiotics of this complex differ from each other in the type of fatty acyl unit attached to the N-terminal tryptophan. The cyclic peptide core of each antibiotic is the same (Fig. 1)1). Antibiotic activity of these compounds requires both the fatty acyl group and the cyclic peptide portion of the molecule z). During the study of the biosynthesis of these factors, it was found that the availability of branched chain fatty acid precursors determined the relative amount of each factor produced by the culture. This report describes that phenomenon and identifies two new factors produced by precursing the culture. S. roseosporus was grown in complex vegetative medium for 2 days, then transferred to a complex fermentation medium1) and grown for 5 to 7 days at 30°C. Additions to the culture were made aseptically after 2 days growth in the fermentation medium. As shown in Fig. 2a, the normal factor profile consists of approximately 1: 1.5: 1 of factors Cl : C2: C3. When the culture was precursed with valine, the proportion of C2 increased dramatically when compared to the other factors (Fig. 2b). Likewise, when isoleucine was added, the amount of Cl and C3 was enhanced (Fig. 2c). These results indicate that the availability of these amino acids to serve as branched chain fatty acid primers determines the type and proportion of factors produced by this culture. No detectable amounts of iso-odd carbon chain branched fatty acyl antibiotic was made by the culture. However, when leucine was added to the fermentation, two new factors (X and Y, Fig. 2d) were produced. These two compounds were found to have biological activity as determined by stream splitting studies (data not shown). The biological activity was lost when these factors were incubated with the broth of Actinoplanes utahensis which possesses an enzyme that removes the fatty acyl moieties from the other C factors'). The two new factors were isolated by concentration on Diaion HP-20 followed by pre-

Role of branched chain fatty acid precursors in regulating factor profile in the biosynthesis of A21978 C complex.