An unusually large multifunctional polypeptide in the erythromycin-producing polyketide synthase of Saccharopolyspora erythraea

Erythromycin A, a clinically important polyketide antibiotic, is produced by the Gram-positive bacterium Saccharopolyspora erythraea. In an arrangement that seems to be generally true of antibiotic biosynthetic genes in Streptomyces and related bacteria like S. erythraea, the ery genes encoding the biosynthetic pathway to erythromycin are clustered around the gene (ermE) that confers self-resistance on S. erythraea. The aglycone core of erythromycin A is derived from one propionyl-CoA and six methylmalonyl-CoA units, which are incorporated head-to-tail into the growing polyketide chain, in a process similar to that of fatty-acid biosynthesis, to generate a macrolide intermediate, 6-deoxyerythronolide B. 6-Deoxyerythronolide B is converted into erythromycin A through the action of specific hydroxylases, glycosyltransferases and a methyltransferase. We report here the analysis of about 10 kilobases of DNA from S. erythraea, cloned by chromosome 'walking' outwards from the erythromycin-resistance determinant ermE, and previously shown to be essential for erythromycin biosynthesis. Partial sequencing of this region indicates that it encodes the synthase. Our results confirm this, and reveal a novel organization of the erythromycin-producing polyketide synthase, which provides further insight into the mechanism of chain assembly.     

Host tree unsuitability recognized by pine shoot beetles in flight

Summary In spring, the landing rate of flying European pine shoot beetles,Tomicus piniperda L., on injured Scots pine diminishes as colonization continues. This is due to olfactory cues that indicate progressive host degradation. Verbenone was shown to play a role in the beetle's recognition of this unsuitability of a formerly suitable host, since the compound was increasingly released from colonized tree sections as they aged, but not from uninfested sections. Also, the release of verbenone at natural rates in the forest inhibited the attraction of beetles to host monoterpenes.     

Observations on the toxicity and metabolic relationships of polygodial,the chemical defense of the nudibranchDendrodoris limbata

Summary Polygodial (1), the defense metabolite stored in the skin of the nudibranchDendrodoris limbata, is toxic for the mollusc itself when injected into the hepatopancreas. Biosynthetic experiments using labeled mevalonic acid were devised to investigate a possible metabolic relationship between1 and the mixture of sesquiterpenoidic esters2, stored in the hepatopancreas. The results suggest that1 and2 are biosynthesized by independent pathways.Thanks are due to G. Villani for supplyingDendrodoris limbata and to A. Trabucco for technical assistance.     

Presence of serum proteins in submaxillary duct perfusate

The secretory activity of the main excretory duct of rat submaxillary gland was investigated by the technique of luminal perfusion. Immunologic studies of the perfusate revealed the presence of serum antigens and the absence of intrinsic submaxillary gland antigens. It is suggested that the submaxillary duct permits passive transport of serum proteins to saliva from serum.     

Effects of butyrate and insulin and their interaction on the DNA synthesis of rumen epithelial cells in culture

Summary Rumen epithelial cells (REC) were incubated in the presence of various concentrations of butyrate or insulin or with both of them, to obtain information on their effect on the DNA synthesis of cultured cells. The 24-h values of³H-thymidine incorporation into cellular DNA were measured in the presence of butyrate, insulin or butyrate plus insulin. While butyrate reduced DNA synthesis, insulin produced an increase over the control. Combined butyrate plus insulin treatment influenced the incorporation of label in accordance with the relative proportion of these two substances.     

The molecular mechanism by which insulin stimulates glycogen synthesis in mammalian skeletal muscle

The ability of insulin to promote the phosphorylation of some proteins and the dephosphorylation of others is paradoxical. An insulin-stimulated protein kinase is shown to activate the type-1 protein phosphatase that controls glycogen metabolism, by phosphorylating its regulatory subunit at a specific serine. Furthermore, the phosphorylation of this residue is stimulated by insulin in vivo. Increased and decreased phosphorylation of proteins by insulin can therefore be explained through the same basic underlying mechanism.