Negative Correlation between Lipid Content and Antibiotic Activity inStreptomyces: General Rule and Exceptions

Streptomycetes are well known antibiotic producers and are among the rare prokaryotes able to store carbon as lipids. Previous comparative studies of the weak antibiotic producerStreptomyces lividanswith itsppkmutant and withStreptomyces coelicolor, which both produce antibiotics, suggested the existence of a negative correlation between total lipid content and the ability to produce antibiotics. To determine whether such a negative correlation can be generalized to otherStreptomycesspecies, fifty-four strains were picked randomly and grown on modified R2YE medium, limited in phosphate, with glucose or glycerol as the main carbon source. The total lipid content and antibiotic activity againstMicrococcus luteuswere assessed for each strain. This study revealed that the ability to accumulate lipids was not evenly distributed among strains and that glycerol was more lipogenic than glucose and had a negative impact on antibiotic biosynthesis. Furthermore, a statistically significant negative Pearson correlation between lipid content and antibiotic activity could be established for most strains, but a few strains escape this general law. These exceptions are likely due to limits and biases linked to the type of test used to determine antibiotic activity, which relies exclusively onMicrococcus luteussensitivity. They are characterized either by high lipid content and high antibiotic activity or by low lipid content and undetectable antibiotic activity againstMicrococcus luteus. Lastly, the comparative genomic analysis of two strains with contrasting lipid content, and both namedStreptomyces antibioticus(DSM 41,481 and DSM 40,868, which we found to be phylogenetically related toStreptomyces lavenduligriseus),indicated that some genetic differences in various pathways related to the generation/consumption of acetylCoA could be responsible for such a difference.