TABLE 3.
Effect of the lack of OppA2, the lack of the pSCL4 plasmid, or the lack of both pSCL4 and OppA2 on the transcription of the hlm genes for holomycin biosynthesisa
| Mutant | Gene |
Mc |
BH false-discovery rate-corrected P value |
Fold change |
Gene functionb | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| 22.5 h | 46.5 h | 60 h | 22.5 h | 46.5 h | 60 h | 22.5 h | 46.5 h | 60 h | |||
| S. clavuligerus ΔoppA2::aac | hlmA | 0.93 | 0.59 | 0.58 | 8.1E−01 | 8.2E−01 | 8.7E−01 | 1.90 | 1.51 | 1.50 | Acyltransferase |
| hlmB | 1.19 | 1.54 | 0.48 | 6.9E−01 | 3.5E−01 | 8.8E−01 | 2.28 | 2.92 | 1.39 | Acyl-CoA dehydrogenase | |
| hlmC | 0.72 | 0.62 | 0.39 | 8.5E−01 | 7.8E−01 | 9.1E−01 | 1.64 | 1.54 | 1.31 | Thiosterase | |
| hlmD | 0.76 | 0.25 | 0.58 | 8.3E−01 | 9.2E−01 | 8.5E−01 | 1.69 | 1.19 | 1.49 | Oxidoreductase | |
| hlmE | 0.79 | 0.41 | 063 | 8.4E−01 | 8.8E−01 | 8.5E−01 | 1.73 | 1.33 | 1.54 | NRPS | |
| hlmF | 1.34 | 0.42 | 0.45 | 7.5E−01 | 9.0E−01 | 9.2E−01 | 2.52 | 1.34 | 1.37 | Cys-decarboxylase like | |
| hlmG | 0.56 | 0.18 | 0.47 | 9.0E−01 | 9.5E−01 | 8.9E−01 | 1.48 | 1.13 | 1.39 | Globin | |
| hlmH | 1.91 | 0.98 | 0.53 | 4.4E−01 | 6.3E−01 | 8.8E−01 | 3.76 | 1.97 | 1.45 | MFS transporter | |
| hlmI | 1.44 | 0.83 | 0.68 | 6.7E−01 | 6.9E−01 | 8.3E−01 | 2.72 | 1.78 | 1.60 | Thioredoxin reductase | |
| hlmK | 0.50 | 1.93 | 3.07 | 9.1E−01 | 2.5E−01 | 1.3E−01 | 1.42 | 3.80 | 8.35 | Thiosterase domain | |
| hlmL | 1.77 | 0.61 | 0.37 | 1.8E−03 | 2.7E−01 | 6.7E−01 | 3.42 | 1.52 | 1.29 | Condensation domain | |
| hlmM | 1.67 | 0.42 | 0.15 | 6.8E−03 | 5.4E−01 | 9.1E−01 | 3.18 | 1.33 | 1.11 | LuxR-type regulator | |
| S. clavuligerus pSCL4− | hlmA | 3.60 | 4.01 | 2.78 | 1.27E−02 | 4.34E−03 | 3.95E−02 | 12.13 | 16.12 | 6.84 | Acyltransferase |
| hlmB | 2.44 | 3.01 | 0.99 | 6.47E−02 | 1.62E−02 | 4.75E−01 | 5.42 | 8.03 | 1.99 | Acyl-CoA dehydrogenase | |
| hlmC | 3.72 | 4.49 | 2.23 | 4.72E−03 | 6.43E−04 | 6.86E−02 | 13.19 | 22.44 | 4.69 | Thiosterase | |
| hlmD | 3.52 | 4.08 | 2.30 | 6.29E−03 | 1.34E−03 | 5.47E−02 | 11.45 | 16.92 | 4.92 | Oxidoreductase | |
| hlmE | 4.06 | 4.80 | 2.99 | 3.38E−03 | 5.13E−04 | 1.89E−02 | 16.62 | 27.79 | 7.94 | NRPS | |
| hlmF | 4.33 | 5.17 | 3.24 | 1.06E−02 | 1.96E−03 | 4.05E−02 | 20.15 | 36.11 | 9.42 | Cys-decarboxylase like | |
| hlmG | 4.23 | 4.87 | 3.09 | 2.63E−03 | 5.09E−04 | 1.67E−02 | 18.77 | 29.15 | 8.53 | Globin | |
| hlmH | 3.37 | 5.10 | 3.87 | 1.51E−02 | 3.10E−04 | 3.21E−03 | 10.31 | 34.35 | 14.64 | MFS transporter | |
| hlmI | 3.57 | 5.46 | 3.84 | 8.91E−03 | 1.22E−04 | 3.01E−03 | 11.84 | 44.08 | 14.28 | Thioredoxin reductase | |
| hlmK | 2.05 | 2.57 | 1.16 | 1.49E−01 | 4.82E−02 | 4.11E−01 | 4.14 | 5.93 | 2.24 | Thiosterase domain | |
| hlmL | 0.82 | 1.18 | 1.26 | 6.94E−02 | 6.63E−03 | 3.00E−03 | 1.77 | 2.26 | 2.40 | Condensation domain | |
| hlmM | 0.88 | 1.75 | 1.25 | 7.32E−02 | 3.78E−04 | 5.98E−03 | 1.84 | 3.36 | 2.38 | LuxR-type regulator | |
| S. clavuligerus ΔoppA2::aac pSCL4− | hlmA | 6.17 | 3.03 | 7.06 | 4.40E−02 | 7.10E−01 | 7.80E−02 | 72.16 | 8.16 | 133.56 | Acyltransferase |
| hlmB | 5.14 | 2.67 | 4.90 | 3.40E−02 | 9.20E−01 | 7.70E−02 | 35.30 | 6.38 | 29.88 | Acyl-CoA dehydrogenase | |
| hlmC | 5.69 | 3.25 | 6.10 | 5.10E−01 | 5.50E−01 | 7.80E−02 | 51.78 | 9.49 | 68.76 | Thiosterase | |
| hlmD | 5.73 | 2.92 | 5.79 | 4.50E−01 | 5.80E−01 | 9.80E−02 | 53.21 | 7.56 | 55.47 | Oxidoreductase | |
| hlmE | 6.24 | 3.30 | 6.75 | 4.80E−02 | 4.60E−01 | 9.60E−02 | 75.48 | 9.86 | 108.00 | NRPS | |
| hlmF | 7.12 | 3.97 | 7.53 | 4.70E−02 | 6.90E−01 | 1.30E−01 | 138.63 | 15.64 | 185.17 | Cys-decarboxylase like | |
| hlmG | 5.64 | 3.21 | 6.10 | 7.20E−03 | 4.00E−01 | 2.40E−01 | 49.88 | 9.24 | 68.39 | Globin | |
| hlmH | 4.77 | 2.89 | 6.54 | 7.20E−01 | 2.00E−01 | 3.40E−01 | 27.35 | 7.39 | 92.89 | MFS transporter | |
| hlmI | 4.49 | 3.24 | 7.13 | 8.60E−01 | 1.90E−01 | 1.60E−01 | 22.47 | 9.47 | 140.36 | Thioredoxin reductase | |
| hlmK | 3.61 | 2.23 | 4.16 | 6.70E−01 | 9.30E−03 | 2.20E−01 | 12.23 | 4.71 | 17.89 | Thiosterase domain | |
| hlmL | 1.79 | 1.29 | 2.41 | 3.20E−01 | 2.30E−03 | 1.30E−01 | 3.45 | 2.44 | 5.30 | Condensation domain | |
| hlmM | 1.89 | 1.16 | 3.00 | 3.40E−02 | 3.90E−01 | 3.30E−02 | 3.70 | 2.24 | 8.02 | LuxR-type regulator | |
a
The hlmA-to-hlmM genes correspond to SCLAV_5267 to SCLAV_5278 in the StrepDB database. Values for the mutants are given relative to those for S. clavuligerus ATCC 27064, taken as 1.0.
b
Acyl-CoA, acyl coenzyme A; NRPS, nonribosomal peptide synthetase; MFS, major facilitator superfamily.