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

MutantGeneMcBH false-discovery rate-corrected P valueFold changeGene functionb
22.5 h46.5 h60 h22.5 h46.5 h60 h22.5 h46.5 h60 h
S. clavuligerus ΔoppA2::aachlmA0.930.590.588.1E−018.2E−018.7E−011.901.511.50Acyltransferase
hlmB1.191.540.486.9E−013.5E−018.8E−012.282.921.39Acyl-CoA dehydrogenase
hlmC0.720.620.398.5E−017.8E−019.1E−011.641.541.31Thiosterase
hlmD0.760.250.588.3E−019.2E−018.5E−011.691.191.49Oxidoreductase
hlmE0.790.410638.4E−018.8E−018.5E−011.731.331.54NRPS
hlmF1.340.420.457.5E−019.0E−019.2E−012.521.341.37Cys-decarboxylase like
hlmG0.560.180.479.0E−019.5E−018.9E−011.481.131.39Globin
hlmH1.910.980.534.4E−016.3E−018.8E−013.761.971.45MFS transporter
hlmI1.440.830.686.7E−016.9E−018.3E−012.721.781.60Thioredoxin reductase
hlmK0.501.933.079.1E−012.5E−011.3E−011.423.808.35Thiosterase domain
hlmL1.770.610.371.8E−032.7E−016.7E−013.421.521.29Condensation domain
hlmM1.670.420.156.8E−035.4E−019.1E−013.181.331.11LuxR-type regulator
S. clavuligerus pSCL4hlmA3.604.012.781.27E−024.34E−033.95E−0212.1316.126.84Acyltransferase
hlmB2.443.010.996.47E−021.62E−024.75E−015.428.031.99Acyl-CoA dehydrogenase
hlmC3.724.492.234.72E−036.43E−046.86E−0213.1922.444.69Thiosterase
hlmD3.524.082.306.29E−031.34E−035.47E−0211.4516.924.92Oxidoreductase
hlmE4.064.802.993.38E−035.13E−041.89E−0216.6227.797.94NRPS
hlmF4.335.173.241.06E−021.96E−034.05E−0220.1536.119.42Cys-decarboxylase like
hlmG4.234.873.092.63E−035.09E−041.67E−0218.7729.158.53Globin
hlmH3.375.103.871.51E−023.10E−043.21E−0310.3134.3514.64MFS transporter
hlmI3.575.463.848.91E−031.22E−043.01E−0311.8444.0814.28Thioredoxin reductase
hlmK2.052.571.161.49E−014.82E−024.11E−014.145.932.24Thiosterase domain
hlmL0.821.181.266.94E−026.63E−033.00E−031.772.262.40Condensation domain
hlmM0.881.751.257.32E−023.78E−045.98E−031.843.362.38LuxR-type regulator
S. clavuligerus ΔoppA2::aac pSCL4hlmA6.173.037.064.40E−027.10E−017.80E−0272.168.16133.56Acyltransferase
hlmB5.142.674.903.40E−029.20E−017.70E−0235.306.3829.88Acyl-CoA dehydrogenase
hlmC5.693.256.105.10E−015.50E−017.80E−0251.789.4968.76Thiosterase
hlmD5.732.925.794.50E−015.80E−019.80E−0253.217.5655.47Oxidoreductase
hlmE6.243.306.754.80E−024.60E−019.60E−0275.489.86108.00NRPS
hlmF7.123.977.534.70E−026.90E−011.30E−01138.6315.64185.17Cys-decarboxylase like
hlmG5.643.216.107.20E−034.00E−012.40E−0149.889.2468.39Globin
hlmH4.772.896.547.20E−012.00E−013.40E−0127.357.3992.89MFS transporter
hlmI4.493.247.138.60E−011.90E−011.60E−0122.479.47140.36Thioredoxin reductase
hlmK3.612.234.166.70E−019.30E−032.20E−0112.234.7117.89Thiosterase domain
hlmL1.791.292.413.20E−012.30E−031.30E−013.452.445.30Condensation domain
hlmM1.891.163.003.40E−023.90E−013.30E−023.702.248.02LuxR-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.