Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data from Both Streptomyces ansochromogenes and ΔwblA
Abstract
:1. Introduction
2. Results and Discussion
2.1. Sequencing and AntiSMASH Analysis of S. Ansochromogenes 7100 Genome
2.2. Genome-Wide Differentially Expressed Genes in ΔwblA
2.3. The Silent Nikkomycin Pathway and the Activated Tylosin Analogue Compounds (TACs) Biosynthetic Pathway in ΔwblA
2.4. Production of an Anthracycline Antibiotic Oviedomycin Activated by Disrupting Genes san7324 plus san7324L
2.5. Understanding on Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data
3. Materials and Methods
3.1. Strains and Growth Condition
3.2. HPLC Analysis of Oviedomycin
3.3. PacBio Sequencing, Assembly and Gene Annotation
3.4. RNA Isolation, Library Construction and Sequencing
3.5. Quality Control and Reads Mapping to the Reference Genome
3.6. Quantification of Gene Expression Level and Differential Expression Analysis
3.7. RT-PCR Analysis
3.8. Data Availability
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Region | Type | From (bp) | To (bp) | Most Similar Known Cluster | Similarity |
---|---|---|---|---|---|
Region 1 | NRPS, NRPS-like, betalactone, nucleoside | 118,096 | 202,793 | neopolyoxin C | 100% |
Region 2 | lanthipeptide-class-ii, terpene | 287,202 | 318,846 | heronamide A/heronamide B/heronamide C/heronamide D/heronamide E/heronamide F | 8% |
Region 3 | NRPS, T1PKS, terpene | 413,811 | 476,353 | eponemycin | 21% |
Region 4 | ectoine | 579,945 | 589,601 | ectoine | 75% |
Region 5 | NRPS-like | 681,454 | 723,406 | livipeptin | 100% |
Region 6 | terpene, T1PKS, PKS-like, NRPS, RiPP-like | 941,834 | 1,090,502 | filipin | 38% |
Region 7 | RiPP-like | 1,402,262 | 1,411,931 | - | |
Region 8 | T2PKS, T1PKS | 1,481,390 | 1,632,620 | spiramycin | 46% |
Region 9 | terpene | 1,658,532 | 1,682,854 | hopene | 92% |
Region 10 | butyrolactone | 2,066,935 | 2,076,146 | lactonamycin | 5% |
Region 11 | siderophore | 2,110,497 | 2,123,136 | - | - |
Region 12 | terpene | 2,269,830 | 2,290,914 | ashimides | 16% |
Region 13 | butyrolactone | 2,300,561 | 2,311,180 | prejadomycin/rabelomycin/gaudimycin C/gaudimycin D/UWM6/ gaudimycin A | 6% |
Region 14 | RiPP-like | 2,317,869 | 2,327,714 | streptonigrin | 5% |
Region 15 | butyrolactone | 2,408,057 | 2,418,502 | - | - |
Region 16 | NRPS, NAPAA | 2,440,769 | 2,482,644 | stenothricin | 13% |
Region 17 | siderophore | 2,636,536 | 2,648,477 | - | - |
Region 18 | thioamitides, RiPP-like | 3,052,710 | 3,074,720 | A-503083 A/A-503083 B/A-503083 E/A-503083 F | 3% |
Region 19 | terpene | 3,258,980 | 3,279,405 | albaflavenone | 100% |
Region 20 | NRPS, RRE-containing | 3,416,101 | 3,487,684 | granaticin | 8% |
Region 21 | T2PKS | 4,177,007 | 4,248,593 | oviedomycin | 95% |
Region 22 | betalactone | 4,526,013 | 4,553,501 | divergolide A/divergolide B/divergolide C/divergolide D | 6% |
Region 23 | terpene | 5,147,528 | 5,167,076 | mitomycin | 3% |
Region 24 | siderophore | 5,623,772 | 5,635,544 | desferrioxamin B/desferrioxamine E | 83% |
Region 25 | melanin, RRE-containing, phosphonate | 5,736,851 | 5,791,306 | fosfazinomycin A | 78% |
Region 26 | ectoine | 6,302,336 | 6,311,857 | showdomycin | 52% |
Region 27 | T2PKS | 6,332,547 | 6,405,060 | spore pigment | 83% |
Region 28 | terpene | 6,423,141 | 6,443,139 | neocarazostatin A | 100% |
Region 29 | ectoine | 6,762,458 | 6,772,862 | ectoine | 100% |
Region 30 | NRPS-like, NRPS, terpene | 7,351,300 | 7,421,452 | enduracidin | 4% |
Region 31 | T3PKS | 7,458,394 | 7,497,631 | herboxidiene | 7% |
Region 32 | T1PKS, NRPS, PKS-like | 7,669,936 | 7,736,833 | LL-D49194α1 (LLD) | 3% |
Region 33 | melanin | 7,963,719 | 7,974,099 | melanin | 57% |
Region 34 | T1PKS | 8,145,007 | 8,259,932 | sceliphrolactam | 92% |
Region 35 | T3PKS, lanthipeptide-class-i, T1PKS | 8,397,854 | 8,505,277 | A-47934 | 8% |
Region 36 | lanthipeptide-class-i | 8,764,849 | 8,790,087 | primycin | 8% |
Region 37 | butyrolactone | 8,824,305 | 8,835,291 | - | |
Region 38 | lassopeptide | 8,842,116 | 8,864,247 | SSV-2083 | 36% |
Region 39 | NRPS, lassopeptide | 8,883,560 | 8,950,374 | achromosin | 100% |
Region 40 | terpene | 9,046,490 | 9,072,076 | carotenoid | 63% |
Region 41 | lassopeptide | 9,413,607 | 9,436,052 | - | - |
Gene ID | Step or Gene Name | KO_id in KEGG Pathway | Fold Change (ΔwblA_24 h/WT_24 h) | Fold Change (ΔwblA_48 h/WT_48 h) | Start | End | Strand | Function | |
---|---|---|---|---|---|---|---|---|---|
ctg1_1366 | step 1 | K00626 | 2.9 | 2.5 | 1701042 | 1702256 | − | acetyl-CoA C-acetyltransferase | |
ctg1_2557 | step 1 | K00626 | 1.0 | 8.3 | 3127039 | 3128238 | − | acetyl-CoA C-acetyltransferase | |
ctg1_4516 | step 1 | K00626 | 1.6 | 7.3 | 5304370 | 5305590 | − | acetyl-CoA C-acetyltransferase | |
ctg1_2421 | step 2 | K00826 | 1.7 | 2.6 | 2966975 | 2968063 | − | branched-chain amino acid aminotransferase | |
ctg1_1739 | step 3 | K00263 | 0.6 | 0.6 | 2144241 | 2145296 | + | leucine dehydrogenase | |
ctg1_4276 | step 4 | K01692 | 0.1 | 0.2 | 5031893 | 5032639 | + | enoyl-CoA hydratase | |
ctg1_5640 | step 4 | K01692 | 0.2 | 0.5 | 6578023 | 6578784 | − | enoyl-CoA hydratase | |
ctg1_6838 | step 4 | K01692 | 0.1 | 0.3 | 7905240 | 7906040 | + | enoyl-CoA hydratase | |
ctg1_7415 | step 4 | K01692 | 0.2 | 0.7 | 8560092 | 8560883 | + | enoyl-CoA hydratase | |
ctg1_4798 | step 5 | K01640 | 6.5 | 3.9 | 5638643 | 5639584 | − | hydroxymethylglutaryl-CoA lyase | |
ctg1_6290 | step 6 | K01907 | 3.2 | 0.7 | 7305337 | 7307313 | + | acetoacetyl-CoA synthetase | |
ctg1_6691 | step 7 | K00020 | 0.4 | 1.3 | 7743630 | 7744517 | − | 3-hydroxyisobutyrate dehydrogenase | |
ctg1_6874 | step 8 | K00128 | 7.7 | 2.1 | 7947480 | 7948802 | + | aldehyde dehydrogenase (NAD+) | |
ctg1_2035 | step 9 | K01847 | 0.6 | 14.6 | 2497253 | 2499067 | + | methylmalonyl-CoA mutase | |
ctg1_2036 | step 9 | K01847 | 1.0 | 12.8 | 2499067 | 2501241 | + | methylmalonyl-CoA mutase | |
ctg1_2543 | step 9 | K01848 | 2.8 | 1.7 | 3114436 | 3116136 | − | methylmalonyl-CoA mutase, N-terminal domain | |
ctg1_4919 | step 10 | K01965 | 15.9 | 2.0 | 5767295 | 5768551 | − | propionyl-CoA carboxylase alpha chain | |
ctg1_1275 | PKS1 | * | 90.0 | 7.0 | 1574987 | 1588348 | − | Polyketone synthase | |
ctg1_1274 | PKS2 | * | 27.4 | 3.7 | 1568736 | 1574990 | − | Polyketone synthase | |
ctg1_1273 | PKS3 | * | 32.9 | 5.0 | 1557006 | 1568672 | − | Polyketone synthase | |
ctg1_1272 | PKS4 | * | 37.7 | 8.4 | 1552212 | 1556942 | − | Polyketone synthase | |
ctg1_1271 | PKS5 | * | 20.3 | 4.2 | 1545995 | 1552108 | − | Polyketone synthase | |
ctg1_1284 | Orf9 | * | 14.4 | 1.7 | 1599380 | 1599619 | − | ferredoxin | |
ctg1_1285 | Orf10 | * | 25.7 | 1.5 | 1599659 | 1600816 | − | cytochrome p450 | |
ctg1_1277 | Orf2 | * | 72.2 | 5.3 | 1590321 | 1591208 | + | dTDP-glucose_synthase | |
ctg1_1278 | Orf3 | * | 192.0 | 11.3 | 1591278 | 1592276 | + | dTDP-glucose 4,6-dehydratase | |
ctg1_1287 | Orf12 | * | 39.2 | 4.3 | 1601980 | 1602597 | + | dTDP-4-dehydrorhamnose 3,5-epimerase | |
ctg1_1280 | Orf5 | * | 2.8 | 1.6 | 1594851 | 1595702 | + | 4-ketoreductase_in_D-allose_pathway | |
ctg1_1281 | Orf6 | * | 22.3 | 4.1 | 1595710 | 1597002 | − | D-allose_glycosyltransferase | |
ctg1_1282 | Orf7 | * | 40.3 | 3.8 | 1597061 | 1598248 | − | 2’OH-methyltransferase | |
ctg1_1286 | Orf11 | * | 40.5 | 3.5 | 1601199 | 1601969 | + | methyltransferase | |
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Li, Y.; Yu, H.; Guan, H.; Li, J.; Zhang, J.; Xiang, H.; Li, J.; Tan, H. Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data from Both Streptomyces ansochromogenes and ΔwblA. Antibiotics 2021, 10, 1097. https://doi.org/10.3390/antibiotics10091097
Li Y, Yu H, Guan H, Li J, Zhang J, Xiang H, Li J, Tan H. Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data from Both Streptomyces ansochromogenes and ΔwblA. Antibiotics. 2021; 10(9):1097. https://doi.org/10.3390/antibiotics10091097
Chicago/Turabian StyleLi, Yue, Haiying Yu, Hanye Guan, Jingjing Li, Jihui Zhang, Hua Xiang, Jine Li, and Huarong Tan. 2021. "Activation of Cryptic Antibiotic Biosynthetic Gene Clusters Guided by RNA-seq Data from Both Streptomyces ansochromogenes and ΔwblA" Antibiotics 10, no. 9: 1097. https://doi.org/10.3390/antibiotics10091097