171:. However, when used in conjunction with one another, the streptogramins can inhibit bacterial growth and are bactericidal. Streptogramin A first binds to the peptidyl transferase domain of the 50s ribosomal subunit, preventing the early events of elongation. The binding of streptogramin A causes a conformational change that increases the ribosomal binding activity of streptogramin B 100-fold. Upon binding the ribosome (which streptogramin B can accomplish at any stage of protein synthesis), streptogramin B prevents protein chain extension and can initiate the release of incomplete peptides. When both streptogramins are bound to the ribosome, they form an extremely stable ternary complex.
86:
63:(lactone-cyclized peptides). While structurally different, these two groups of antibiotics act synergistically, providing greater antibiotic activity than the combined activity of the separate components. These antibiotics have until recently been commercially manufactured as feed additives in agriculture, although today there is increased interest in their ability to combat antibiotic-resistant bacteria, particularly vancomycin-resistant bacteria.
363:
Sighel, Denise; Notarangelo, Michela; Aibara, Shintaro; Re, Angela; Ricci, Gianluca; Guida, Marianna; Soldano, Alessia; Adami, Valentina; Ambrosini, Chiara; Broso, Francesca; Rosatti, Emanuele
Filiberto; Longhi, Sara; Buccarelli, Mariachiara; d'Alessandris, Quintino G.; Giannetti, Stefano; Pacioni,
413:
Sighel, Denise; Battistini, Giulia; Rosatti, Emanuele
Filiberto; Vigna, Jacopo; Pavan, Matteo; Belli, Romina; Peroni, Daniele; Alessandrini, Federica; Longhi, Sara; Pancher, Michael; Rorbach, Joanna; Moro, Stefano; Quattrone, Alessandro; Mancini, Ines (2023). "Streptogramin a derivatives as
92:
The streptogramin A PKS-NRPS is composed of 6 proteins: VirA contains modules 1 though 6; VirF, VirG, and VirH contain modules 6 through 10; VirI is the AT domain that acts for every PKS module; and VirJ contains the TE domain. The starter unit for the biosynthesis of streptogramin A is
117:
to add a methyl group to position 12 on the macromolecule. The mechanism of the reaction is proposed below. VirC and HMG-CoA synthase bear striking structural similarities and while the mechanism for VirC is not known, it can be proposed to be similar to that of HMG-CoA synthase.
174:
Recently, it has been reported how inhibition of the mitochondrial ribosome by streptogramins A (alone or in combination with streptogramins B) can block glioblastoma stem cell growth, thus allowing for potential repurposing of these antibiotics as antineoplastic agents.
75:
in nature, but contains some amino acid components as well. Its gene cluster codes for a hybrid PKS-NRPS protein that consists of eight PKS modules and two NRPS modules. Other enzymes are required for tailoring of streptogramin A, particularly for the unusual
130:
Such an elaborate mechanism of methylation is necessary since SAM is not able to insert a methyl group onto a carbonyl carbon. Another round of malonate extension occurs, followed by the malonate's reaction with an adjacent serine extender to form an
191:
Multiple mechanisms of streptogramin resistance have developed despite
Synercid's fairly recent development. The three major mechanisms of resistance include active efflux, covalent target modification and antibiotic inactivation enzymes.
178:
In 1999 the FDA had approved
Synercid, a drug containing streptogramins A and B in a 7:3 ratio respectively. This intravenously injected drug is used to treat patients with bacteremia caused by vancomycin-resistant
471:
LeFevre, J.; Glass, T.; Kolpak, M.; Kingston, D. (1983). "Biosynthesis of
Antibiotics of the Virginiamycin Family, 2. Assignment of the13C-NMR Spectra of Virginiamycin M1and Antibiotic A2315A".
135:
ring. This reaction is catalyzed by a cyclization domain on the Ser9 NRPS module. The diagram below shows the biogenesis of the oxazole ring from serine and malonate.
364:
Simone; Ricci-Vitiani, Lucia; Rorbach, Joanna; Pallini, Roberto; Roulland, Sandrine; Amunts, Alexey; Mancini, Ines; Modelska, Angelika; Quattrone, Alessandro (2021).
293:
Kingston, D.; Kolpak, M.; LeFevre, J.; Borup-Grochtman, I. (1983). "Biosynthesis of
Antibiotics of the Virginiamycin Family. 3. Biosynthesis of Virginiamycin M1".
156:
47:. The streptogramin family of antibiotics consists of two distinct groups: group A antibiotics contain a 23-membered unsaturated ring with
113:
residue into the growing polyketide chain, followed by two more rounds of chain extension with malonate. At this point, four enzymes use
124:
501:
232:
Mukhtar, T. A.; Wright, G.D. (2005). "Streptogramins, Oxazolidinones, and Other
Inhibitors of Bacterial Protein Synthesis".
85:
241:
43:
511:
246:
147:
155:
449:
345:
506:
441:
395:
337:
259:
80:
reaction. The figure below shows the origins of the synthetic components of streptogramin A.
480:
431:
423:
385:
377:
329:
302:
251:
209:
320:
Vannuffel, P.; Cocito, C. (1996). "Mechanism of action of streptogramins and macrolides".
56:
390:
365:
168:
102:
94:
495:
453:
333:
38:
17:
349:
60:
366:"Inhibition of mitochondrial translation suppresses glioblastoma stem cell growth"
427:
414:
mitochondrial translation inhibitors to suppress glioblastoma stem cell growth".
381:
146:
residue is added to the chain, followed by hydroxylation and dehydration to form
105:
and branched-chain keto acid dehydrogenation. Two rounds of chain extension with
77:
34:
114:
72:
123:
445:
399:
263:
341:
106:
484:
436:
306:
143:
132:
110:
52:
48:
255:
150:, which is thought to occur through a reverse Michael-type reaction.
98:
281:
Medicinal
Natural Products: A Biosynthetic Approach
37:within the larger family of antibiotics known as
8:
227:
225:
223:
283:, 2009, John Wiley & Sons Ltd. p450-451
167:By themselves, streptogramins A and B are
435:
389:
245:
275:
273:
41:. They are synthesized by the bacteria
416:European Journal of Medicinal Chemistry
201:
7:
109:follow. An NRPS module introduces a
97:, which is given by the amino acid
25:
334:10.2165/00003495-199600511-00006
154:
122:
84:
1:
428:10.1016/j.ejmech.2022.114979
382:10.1016/j.celrep.2021.109024
187:Resistance to streptogramins
528:
210:"KEGG COMPOUND: C11299"
101:after it has undergone
44:Streptomyces virginiae
502:Macrolide antibiotics
71:Streptogramin A is a
18:Streptogramin group a
181:Enterococcus faecium
27:Group of antibiotics
485:10.1021/np50028a008
307:10.1021/ja00353a041
301:(15): 5106–5110.
256:10.1021/cr030110z
141:
16:(Redirected from
519:
488:
458:
457:
439:
410:
404:
403:
393:
360:
354:
353:
317:
311:
310:
295:J. Am. Chem. Soc
290:
284:
277:
268:
267:
249:
229:
218:
217:
206:
158:
139:
126:
88:
59:antibiotics are
21:
527:
526:
522:
521:
520:
518:
517:
516:
492:
491:
470:
467:
465:Further reading
462:
461:
412:
411:
407:
362:
361:
357:
319:
318:
314:
292:
291:
287:
278:
271:
247:10.1.1.460.6691
231:
230:
221:
208:
207:
203:
198:
189:
165:
69:
31:Streptogramin A
28:
23:
22:
15:
12:
11:
5:
525:
523:
515:
514:
509:
504:
494:
493:
490:
489:
479:(4): 475–480.
466:
463:
460:
459:
405:
355:
312:
285:
279:Dewick, Paul.
269:
240:(2): 529–542.
219:
200:
199:
197:
194:
188:
185:
169:bacteriostatic
164:
163:Mode of action
161:
160:
159:
148:dehydroproline
128:
127:
103:transamination
95:isobutyryl-CoA
90:
89:
68:
65:
39:streptogramins
33:is a group of
26:
24:
14:
13:
10:
9:
6:
4:
3:
2:
524:
513:
510:
508:
505:
503:
500:
499:
497:
486:
482:
478:
474:
469:
468:
464:
455:
451:
447:
443:
438:
433:
429:
425:
421:
417:
409:
406:
401:
397:
392:
387:
383:
379:
375:
371:
367:
359:
356:
351:
347:
343:
339:
335:
331:
327:
323:
316:
313:
308:
304:
300:
296:
289:
286:
282:
276:
274:
270:
265:
261:
257:
253:
248:
243:
239:
235:
228:
226:
224:
220:
215:
214:www.genome.jp
211:
205:
202:
195:
193:
186:
184:
182:
176:
172:
170:
162:
157:
153:
152:
151:
149:
145:
136:
134:
125:
121:
120:
119:
116:
112:
108:
104:
100:
96:
87:
83:
82:
81:
79:
74:
66:
64:
62:
61:depsipeptides
58:
54:
50:
46:
45:
40:
36:
32:
19:
476:
473:J. Nat. Prod
472:
437:11572/364207
419:
415:
408:
373:
370:Cell Reports
369:
358:
325:
321:
315:
298:
294:
288:
280:
237:
233:
213:
204:
190:
180:
177:
173:
166:
137:
129:
91:
70:
67:Biosynthesis
55:bonds while
42:
30:
29:
512:Polyketides
138:Finally, a
78:methylation
35:antibiotics
496:Categories
196:References
115:acetyl-CoA
73:polyketide
454:254336666
328:: 20–30.
242:CiteSeerX
234:Chem. Rev
507:Oxazoles
446:36495628
400:33910005
350:37305530
264:15700955
107:malonate
391:8097689
342:8724813
144:proline
133:oxazole
111:glycine
57:group B
53:peptide
49:lactone
452:
444:
398:
388:
348:
340:
262:
244:
99:valine
450:S2CID
376:(4).
346:S2CID
322:Drugs
442:PMID
396:PMID
338:PMID
260:PMID
51:and
481:doi
432:hdl
424:doi
420:246
386:PMC
378:doi
330:doi
303:doi
299:105
252:doi
238:105
498::
477:46
475:.
448:.
440:.
430:.
422:.
418:.
394:.
384:.
374:35
372:.
368:.
344:.
336:.
326:51
324:.
297:.
272:^
258:.
250:.
236:.
222:^
212:.
183:.
487:.
483::
456:.
434::
426::
402:.
380::
352:.
332::
309:.
305::
266:.
254::
216:.
142:-
140:D
20:)
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.
