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Bacillibactin and Bacillomycin Analogues with Cytotoxicities against Human Cancer Cell Lines from Marine Bacillus sp. PKU-MA00093 and PKU-MA00092

State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Haidian District, Beijing 100191, China
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Mar. Drugs 2018, 16(1), 22; https://doi.org/10.3390/md16010022
Received: 27 November 2017 / Revised: 21 December 2017 / Accepted: 5 January 2018 / Published: 10 January 2018
(This article belongs to the Special Issue Genome Mining and Marine Microbial Natural Products)
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Abstract

Nonribosomal peptides from marine Bacillus strains have received considerable attention for their complex structures and potent bioactivities. In this study, we carried out PCR-based genome mining for potential nonribosomal peptides producers from our marine bacterial library. Twenty-one “positive” strains were screened out from 180 marine bacterial strains, and subsequent small-scale fermentation, HPLC and phylogenetic analysis afforded Bacillus sp. PKU-MA00092 and PKU-MA00093 as two candidates for large-scale fermentation and isolation. Ten nonribosomal peptides, including four bacillibactin analogues (14) and six bacillomycin D analogues (510) were discovered from Bacillus sp. PKU-MA00093 and PKU-MA00092, respectively. Compounds 1 and 2 are two new compounds and the 1H NMR and 13C NMR data of compounds 7 and 9 is first provided. All compounds 110 were assayed for their cytotoxicities against human cancer cell lines HepG2 and MCF7, and the bacillomycin D analogues 710 showed moderate cytotoxicities with IC50 values from 2.9 ± 0.1 to 8.2 ± 0.2 µM. The discovery of 510 with different fatty acid moieties gave us the opportunity to reveal the structure-activity relationships of bacillomycin analogues against these human cancer cell lines. These results enrich the structural diversity and bioactivity properties of nonribosomal peptides from marine Bacillus strains. View Full-Text
Keywords: bacillibactin; bacillomycin; genome mining; marine Bacillus; nonribosomal peptides bacillibactin; bacillomycin; genome mining; marine Bacillus; nonribosomal peptides
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zhou, M.; Liu, F.; Yang, X.; Jin, J.; Dong, X.; Zeng, K.-W.; Liu, D.; Zhang, Y.; Ma, M.; Yang, D. Bacillibactin and Bacillomycin Analogues with Cytotoxicities against Human Cancer Cell Lines from Marine Bacillus sp. PKU-MA00093 and PKU-MA00092. Mar. Drugs 2018, 16, 22.

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