Fig. 1.
A) Comparison of genetic organization of tirandamycin biosynthetic gene clusters in strain TRM44567 and Streptomyces sp.307–9.
Fig. 1.
B) UV spectrum and MS peak in the crude extract of strain TRM44567 in R5 medium.
Table I
TRM44567 secondary metabolite gene cluster prediction.
| Number | Gene cluster position | Lengths (bp) | Typology | Similar gene clusters | Resemblance (%) |
|---|---|---|---|---|---|
| 1 | 8,773-35,720 | 26,948 | butyrolactone, terpene | 2-methylisoborneol | 75 |
| 2 | 214,388-239,491 | 25,104 | lanthipeptide-class-i | - | - |
| 3 | 667,293-708,315 | 41,023 | other | 7-deoxypactamycin | 11 |
| 4 | 744,740-767,544 | 22,805 | lanthipeptide-class-iv | venezuelin | 50 |
| 5 | 811,611-837,822 | 26,212 | amglyccycl, tyrolactone | acarbose | 14 |
| 6 | 1,098,443-1,154,095 | 55,653 | T1PKS, NRPS | jomthonic acid A/B/C | 5 |
| 7 | 1,329,308-1,339,462 | 10,155 | RiPP-like | - | - |
| 8 | 1,355,940-1,397,127 | 41,188 | T3PKS | gobichelin A/B | 16 |
| 9 | 1,541,462-1,565,687 | 24,226 | lanthipeptide-class-i | - | - |
| 10 | 2,467,823-2,476,751 | 8,929 | RiPP-like | - | - |
| 11 | 2,621,822-2,641,748 | 19,927 | Trpene | albaflavenone | 100 |
| 12 | 3,407,363-3,468,045 | 60,683 | siderophore, lipolanthine, T1PKS, lanthipeptide-class-iii, linaridin | kinamycin | 22 |
| 13 | 3,603,223-3,671,199 | 67,977 | NRPS, NRPS-like | thiocoraline | 60 |
| 14 | 3,715,948-3,744,688 | 28,741 | RiPP-like, terpene | ashimides | 12 |
| 15 | 3,772,034-3,793,450 | 21,417 | butyrolactone | γ-butyrolactone | 100 |
| 16 | 3,859,629-3,900,359 | 40,731 | NRPS, NAPAA | stenothricin | 13 |
| 17 | 4,043,123-4,056,246 | 13,124 | siderophore | atakemycin | 6 |
| 18 | 4,127,840-4,168,065 | 40,226 | NRPS-like | lobosamide A/B/C | 4 |
| 19 | 4,646,047-4,672,724 | 26,678 | terpene | hopene | 92 |
| 20 | 4,773,585-4,854,740 | 81,156 | NRPS, T1PKS | tirandamycin | 100 |
| 21 | 5,069,238-5,079,453 | 10,216 | Ripp-like | informatipeptin | 42 |
| 22 | 276,872-347,373 | 70,502 | T2PKS | prejadomycin/gaudimyc in | 29 |
| 23 | 776,140-787,912 | 11,773 | siderophore | desferrioxamin B/E | 83 |
| 24 | 905,539-914,564 | 9,026 | melanin | melanin | 60 |
| 25 | 1,263,341-1,304,207 | 40,867 | T3PKS | s56-p1 | 11 |
| 26 | 1,631,756-1,704,267 | 72,512 | T2PKS | spore pigment | 83 |
| 27 | 2,082,866-2,093,270 | 10,405 | ectoine | ectoine | 100 |
| 28 | 2,295,368-2,314,558 | 19,191 | CDPS | - | - |
| 29 | 2,369,855-2,402,869 | 33,015 | NAPAA | meilingmycin | 2 |
| 30 | 2,970,457-3,010,999 | 40,543 | T3PKS | herboxidiene | 7 |
| 31 | 3094,635-3,115,642 | 21,008 | terpene | desotamide | 9 |
| 32 | 3,430,099-3,508,231 | 78,133 | Melanin, T1PKS, NRPS | scabichelin | 100 |
| 33 | 3,579,258-3,620,409 | 41,152 | T3PKS | alkylresorcinol | 100 |
| 34 | 3,887,970-3,908,680 | 20,711 | CDPS | - | - |
| 35 | 3,920,922-3,964,188 | 43,267 | NRPS, NAPAA | stenothricin | 13 |
Table II
Tirandamycin biosynthesis-related gene function prediction and consistency analysis.
| Number | Gene lengths (bp) | Coding protein | Homologous strain | Resemblance (%) |
|---|---|---|---|---|
| 4283 | 645 | TamK (TetR family regulator) | Streptomyces sp. 307-9 | 99 |
| 4284 | 1494 | TamJ (efflux pump) | Streptomyces sp. 307-9 | 99 |
| 4285 | 1236 | TamI (cytochrome P450) | Streptomyces sp. 307-9 | 99 |
| 4286 | 2814 | TamH (LuxR family regulator) | Streptomyces sp. 307-9 | 97 |
| 4287 | 2094 | TamG (DNA helicase) | Streptomyces sp. 307-9 | 99 |
| 4288 | 1539 | TamF (Prenyltransferase) | Streptomyces sp. 307-9 | 97 |
| 4289 | 831 | TamE (glucosidase) | Streptomyces sp. 307-9 | 98 |
| 4290 | 3165 | TamD (NRPS) | Streptomyces sp. 307-9 | 97 |
| 4291 | 831 | TamC (hypothetical protein) | Streptomyces sp. 307-9 | 97 |
| 4292 | 777 | TamB (alpha/beta fold hydrolase) | Streptomyces sp. 307-9 | 98 |
| 4293 | 8400 | TamAIII | Streptomyces sp. 307-9 | 95 |
| 4294 | 10131 | TamAII | Streptomyces sp. 307-9 | 94 |
| 4295 | 17490 | TamAI | Streptomyces sp. 307-9 | 95 |
| 4296 | 1503 | TamL (FAD-binding oxidoreductase) | Streptomyces sp. 307-9 | 98 |
| 4297 | 234 | TamM (4’-phosphopantetheinyl transferase) | Streptomyces. sp. 307-9 | 97 |
| 4291 | 831 | TamC (hypothetical protein) | Streptomyces sp. 307-9 | 97 |
Fig. 2.
The structure of tirandamycin.
Table III
Comparison of the antibacterial activities of 44567-1 against different targets.
| Number | Target organism | Bacteriostatic activity screening (diameter of inhibition circle) |
|---|---|---|
| 1 | Escherichia coli ATCC® 25922™ | - |
| 2 | Staphylococcus aureus ATCC® 25923™ | 3.0 ± 0.2 mm |
| 3 | Enterococcus faecalis ATCC® 29212™ | - |
| 4 | Klebsiella pneumoniae ATCC® 10031™ | - |
| 5 | Acinetobacter baumannii ATCC® 19606™ | - |
| 6 | Pseudomonas aeruginosa ATCC® 27853™ | 32.0 ± 0.3 mm |
| 7 | Salmonella choleraesu | - |
| 8 | Salmonella castellani | - |
| 9 | Candida albicans ATCC® 64550™ | - |