One ofthe most versatile uses of antibiotics is as potent drugs for clinical application. In recent years, attention has also been paid to agricultural uses of antibiotics, such as for feed additives for protecting plants and livestock against infectious diseases and for accelerating their growth. They are also used as food additives to retain freshness for an extended period. The usefulness of antibiotics is not limited only to our daily needs, but also encompasses our research interests: they offer us remarkable experimental devices for biochemistry novel biochemical tools, which have made a significant contribution to progress in this field (18). Cerulenin, an antibiotic discovered by Hata et al. in 1960, was originally found as an antifungal antibiotic (30). Studies of its mode of action have revealed that it specifically inhibits the biosynthesis of fatty acids and sterols involving yeasts (55, 56). It should be particularly noted that such specificity of cerulenin has been used by investigators in various fields of biochemistry. In this connection, the present review deals with studies, which have hitherto been reported, on the production, isolation, structure, and mode of action of cerulenin and its application as a biochemical tool. Unfortunately, the instability of the antibiotic in the animal body prevents its use in therapy as an antimicrobial agent or as an antilipogenic agent.

The antibiotic cerulenin, a novel tool for biochemistry as an inhibitor of fatty acid synthesis.

Bacterial lipids: Metabolism and membrane homeostasis

Introduction..................................................................... 232 Pertinent Properties of the Cell Envelope ......... ............................. 233 E. coli Fatty Acid Auxotrophs .............. ................................... 233 Specific inhibitors of Fatty Acid Synthesis ......... ............................ 234 LIPID BILAYER PHASE PROPERTIES ........ ............................ 234 Empirical Rules Deduced from Model Systems ........ ......................... 234 Physical Properties of the E. coli Membrane Lipids ....... ..................... 236 Phase transitions............................................................ 236 (i) X-ray diffraction ......................................................... 236 (ii) DSC ..................................................................... 237 (iii) Fluorescent probes ..................................................... 237 (iv) Spin labeling .............. ............................................. 237 Phase separations. (i) Physical studies ......... .............................. 237 (ii) Freeze-fracture electron microscopy ...................................... 239 Lateral movement of lipids ............... ................................... 240 CORRELATIONS BETWEEN MEMBRANE-ASSOCIATED PHYSIOLOGY AND LIPID PHYSICAL PROPERTIES ........ ............................ 240 General Physiology ............................................................ 240 Lactose Transport System ................ ..................................... 240 Relevant properties of lactose transport system ....... ....................... 240 Transport system induction and lipid synthesis ....... ........................ 241 Transport and lipid phase changes ........... ................................ 241 Other Transport Systems .................. .................................... 243 Sugar transport systems ................ ..................................... 243 Amino acid transport systems ............. .................................. 243 Other Physiological Processes ................................................ 243 Lipid requirement for alkaline phosphatase derepression ...... .............. 243 Chemotaxis ............. . .................................................... 244 Initiation of DNA synthesis ............... ................................... 244 Methylgalactoside permease induction ......... .............................. 244 Cell integrity ................. ............................................... 244 Enzymatic activity ........................................................... 244 Requirement for Lipids with Specific Physical Properties ...... ................ 245 Requirement for membrane liquidity ......................................... 245 Minimum UFA content...................................................... 246 Minimum saturated fatty acid content ......... ............................... 246 Significance of temperature-induced alterations in fatty acids ..... ........... 247 REGULATION OF LIPID PHYSICAL PROPERTIES ........................... 247 Possible Lipid Alterations Producing Altered Phase Transitions ..... ........... 247 Sites of Control ................................................................ 247 In Vitro Studies ............................................................... 247 (i) Acyltransferase specificity ............. ................................... 248 (ii) Fatty acid synthetase ................ .................................... 249 In Vivo Studies ................................................................ 249 (i) Determination of fatty acid chain length ........ ........................... 249 (ii) Regulation of the saturated-to-unsaturated fatty acid ratio ..... ........... 250 (iii) Temperature control of fatty acid composition ....... ..................... 250 CONCLUSION.................................................................. 251 LITERATURE CITED .............. ............................................ 252

https://mmbr.asm.org/content/mmbr/39/3/232.full.pdf

Physical properties of membrane lipids: biological relevance and regulation.

Enzymology, genetics, and regulation of membrane phospholipid synthesis in Escherichia coli.

The fluidity of cell membranes and its regulation.

The antibiotic cerulenin markedly inhibits the growth of Escherichia coli. The effects of the antibiotic on cellular syntheses were studied by measuring the incorporation of labeled precursors into lipids and macromolecules. During the first 40 min after the addition of cerulenin to a culture of growing cells, lipid synthesis was inhibited more than 90% and ribonucleic acid and deoxyribonucleic acid synthesis about 25%, whereas protein synthesis was not affected. At later periods after cerulenin addition (1 to 2 h), the inhibition of cell growth and of lipid and protein synthesis was complete. Upon removal of cerulenin from the culture, growth was restored and lipid synthesis resumed more rapidly than did the synthesis of protein. Addition of both palmitate and oleate, but not of either fatty acid alone, reversed the inhibition of growth by cerulenin. These findings support the conclusion that the antibiotic effects of cerulenin are due to a specific inhibition of fatty acid synthesis.

James R. Walker

Papers

Inhibition of Lipid Synthesis in Escherichia coli Cells by the Antibiotic Cerulenin