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Sulfoxanthicillin from the deep-sea derived Penicillium sp. SCSIO sof101: an antimicrobial compound against Gram-positive and -negative pathogens


Natural products along with their analogs have been intensively explored for their antimicrobial potential against ‘ESKAPE’ pathogens. Herein, we report a new natural product with strong antibacterial activity, sulfoxanthocillin (1), along with its decomposed product peniformamide (2), and the known compound xanthocillin X (3) from the deep-sea derived Penicillium sp. SCSIO sof101. The structures of compounds 1 and 2 were determined by extensive spectroscopic analysis. Compound 1 showed significant activity against series pathogens with MIC values ranging 0.06–8.0 μg mL−1. As an artificial unnatural product during the isolation process, compound 2 had lower antimicrobial activity than that of compound 1, which could be attributed to a change in structural modification from an isonitrile group in compound 1 to a formamide group in compound 2. In terms of cytotoxicity, 1 showed relatively low cytotoxicity against human tumor cell lines compared with xanthocillin X (3), suggesting that the sulfate group present in 1 should be a determinant of cytotoxic activities. Overall, sulfoxanthocillin (1) merits further attention as a potential lead compound for anti-infective interventions against Gram-negative and Gram-positive bacterial pathogens.

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This research was funded by National Natural Science Foundation of China (22077128, 22037006, U2106207), Guangdong Provincial Marine Economic Development (Six Major Marine Undertakings) Special Fund Project (GDNRC[2021]54), Key-Area Research and Development Program of Guangdong Province (2020B1111030005), Key Science and Technology Project of Hainan Province (ZDKJ202018), Major Project of Basic and Applied Basic Research of Guangdong Province (2019B030302004), Local Innovation and Entrepreneurship Team Project of Guangdong (2019BT02Y262) and Open Programe of Shenzhen Bay Laboratory (SZBL2021080601006). We thank the analytical facility center of the South China Sea Institute of Oceanology. In particular, we acknowledge Dr. Zhihui Xiao and Dr. Xiaohong Zheng for recording NMR data, and Ms. Aijun Sun, Ms. Yun Zhang, and Xuan Ma for acquisition of HRESIMS data. Additionally, we acknowledge Professor Chang Chen for his kind gifts of pathogenic bacteria Vibrio sp. strains, Professor Jianhua Liu from South China Agricultural University and Professor Nai-Kei Wong from the third People’s Hospital of Shenzhen for the gifts of other pathogenic bacteria.

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Yang, J., Song, Y., Zhou, Z. et al. Sulfoxanthicillin from the deep-sea derived Penicillium sp. SCSIO sof101: an antimicrobial compound against Gram-positive and -negative pathogens. J Antibiot 76, 113–120 (2023).

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