Deciphering the Glycosylation Steps in the Biosynthesis of P-1894B and Grincamycin Isolated from Marine-Derived IStreptomyces lusitanus/I SCSIO LR32

Recently, we re-isolated the glycosylated angucycline antibiotics P-1894B (1) and grincamycin (1′) from the marine-derived Streptomyces lusitanus SCSIO LR32 as potent antitumor agents and identified their biosynthesis gene cluster gcn. Both P-1894B (1) and grincamycin (1′) possess a trisaccharide an...

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Bibliographic Details
Published in:Marine drugs Vol. 22; no. 1
Main Authors: Huang, Hongbo, Zhang, Yun, Song, Yongxiang, Ling, Chunyao, Peng, Siyan, Ding, Bo, Tao, Yiwen, Ju, Jianhua
Format: Journal Article
Language:English
Published: MDPI AG 01.01.2024
Subjects:
Antibiotics
Chemical properties
Glycosylation
Marine bacteria
Metabolites
Microbiological synthesis
Pharmaceutical research
Physiological aspects
Production processes
Streptomyces
China
ISSN:1660-3397, 1660-3397
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Summary:Recently, we re-isolated the glycosylated angucycline antibiotics P-1894B (1) and grincamycin (1′) from the marine-derived Streptomyces lusitanus SCSIO LR32 as potent antitumor agents and identified their biosynthesis gene cluster gcn. Both P-1894B (1) and grincamycin (1′) possess a trisaccharide and a disaccharide moiety comprised of five deoxysugars. In this work, three genes encoding glycosyltransferases (GcnG1, GcnG2, and GcnG3) responsible for the assembly of deoxysugars into angucycline aglycone were identified from the biosynthesis gene cluster gcn. Gene inactivations of gcnG1, gcnG2, gcnG3, and gcnG1G2 by lambda-RED-mediated gene replacements led to the construction of four mutants, in which the glycosyltransferase genes were disrupted, respectively. The metabolites from the mutants were purified and identified, including two new analogues designated as grincamycin U (3a) and V (3′). The sequential glycosylation steps in the biosynthesis of P-1894B (1) and grincamycin (1′) catalyzed by GcnG3, GcnG1, and GcnG2 were elucidated.
ISSN:1660-3397
1660-3397
DOI:10.3390/md22010032