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. 2024 Jan 9:51:kuae014.
doi: 10.1093/jimb/kuae014.

Discovery of Streptomyces species CS-62, a novel producer of the Acinetobacter baumannii selective antibiotic factumycin

Amir Y Alwali  1 , Diane Santos  1 , César Aguilar  1 , Audrey Birch  1 , Lorena Rodriguez-Orduña  2 , Carson B Roberts  1 , Ramya Modi  1 , Cuauhtemoc Licona-Cassani  2 , Elizabeth I Parkinson  3   4
Affiliations

Discovery of Streptomyces species CS-62, a novel producer of the Acinetobacter baumannii selective antibiotic factumycin

Amir Y Alwali et al. J Ind Microbiol Biotechnol. .

Abstract

Narrow-spectrum antibiotics are of great interest given their ability to spare the microbiome and decrease widespread antibiotic resistance compared to broad-spectrum antibiotics. Herein, we screened an in-house library of Actinobacteria strains for selective activity against Acinetobacter baumannii and successfully identified Streptomyces sp. CS-62 as a producer of a natural product with this valuable activity. Analysis of the cultures via high-resolution mass spectrometry and tandem mass spectrometry, followed by comparison with molecules in the Natural Product Atlas and the Global Natural Products Social Molecular Networking platform, suggested a novel natural product. Genome mining analysis initially supported the production of a novel kirromycin derivative. Isolation and structure elucidation via mass spectrometry and Nuclear Magnetic Resonance (NMR) analyses revealed that the active natural product was the known natural product factumycin, exposing omissions and errors in the consulted databases. While public databases are generally very useful for avoiding rediscovery of known molecules, rediscovery remains a problem due to public databases either being incomplete or having errors that result in failed dereplication. Overall, the work describes the ongoing problem of dereplication and the continued need for public database curation.

Keywords: Antibiotics; Biosynthetic gene cluster; Dereplication; Natural products.

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Conflict of interest statement

The authors report no conflicts of interest.

Figures

Graphical Abstract
Graphical Abstract
Fig. 1.
Fig. 1.
MolNET-enhanced Global Natural Products Social Molecular Networking (GNPS) network of Streptomyces sp. CS-62 crude extract from combined media. Colors represent predicted chemical superfamily. Molecules indicated were identified using GNPS.
Fig. 2.
Fig. 2.
Comparison of kirromycin, factumycin, and the Streptomyces sp. CS-62 biosynthetic gene clusters (BGCs). Clinker comparison of the kirromycin BGC from S. collinus sp. Tu 365, the factumycin BGC from Streptomyces sp. WAC5292, and the factumycin BGC from Streptomyces sp. CS62. Colors indicate type of gene.
Fig. 3.
Fig. 3.
Structure of antibiotic natural product from Streptomyces sp. CS-62. Key NMR correlations along with the mass spectra confirm that the isolated natural product from Streptomyces sp. CS62 is factumycin.
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