Aims:  To obtain bacteria with PKS (polyketide synthase) genes and antimicrobial activity from sponges. Methods and Results:  Eighteen bacteria with KS (ketosynthase) genes were identified by polymerase chain reaction (PCR) screening of 98 isolates from South China Sea sponges, Stelletta tenuis, Halichondria rugosa, Dysidea avara and Craniella australiensis. 16S rRNA gene‐based Blast analysis indicated that 15 isolates belonged to the phylum Firmicutes, among which 14 isolates were closely related to genus Bacillus, and 1 to Staphylococcus lentus. Two isolates were identified as actinomycetes, and one as Alcaligenes sp. in the phylum Proteobacteria. The 18 KS domains belong to trans‐AT type I PKS and match PKS of marine bacterial symbionts. The 18 bacteria exhibited broad‐spectrum antimicrobial activities against fungi, gram‐positive and gram‐negative bacteria. A 21·8‐kb PKS gene cluster fragment containing five modules was isolated from the Staphylococcus lentus isolate A75 by screening of a fosmid library. Conclusions:  The PKS gene diversity and different antimicrobial spectra indicate the potential of bacteria associated with South China Sea sponges for diverse polyketide production. Significance and Impact of the Study:  Combined with bioactivity assay the PKS gene‐based approach can be applied to efficient screening of strains of pharmaceutical value and the prediction of related compounds.

This study is the first report on the synergy of anti-MRSA between new erythromycin derivatives and β-lactam antibiotics in vitro. The results show that although the erythromycin derivatives have poor anti-MRSA effects alone, they possess high synergism with oxacillin against MRSA ATCC43300 and clinically isolated MRSA. These novel compounds can significantly reduce the dosage of β-lactam antibiotics against MRSA, while this synergistic effect is different from the combination of β-lactams and β-lactamase inhibitors. The research may provide a new choice for the treatment of infection caused by MRSA and be useful to the research and development of new combination of medicines.

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