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Keywords = glutarimide-containing polyketides

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12 pages, 2172 KB  
Article
The Genomic-Driven Discovery of Glutarimide-Containing Derivatives from Burkholderia gladioli
by Hanna Chen, Xianping Bai, Tao Sun, Xingyan Wang, Youming Zhang, Xiaoying Bian and Haibo Zhou
Molecules 2023, 28(19), 6937; https://doi.org/10.3390/molecules28196937 - 5 Oct 2023
Cited by 10 | Viewed by 2977
Abstract
Glutarimide-containing polyketides exhibiting potent antitumor and antimicrobial activities were encoded via conserved module blocks in various strains that favor the genomic mining of these family compounds. The bioinformatic analysis of the genome of Burkholderia gladioli ATCC 10248 showed a silent trans-AT PKS [...] Read more.
Glutarimide-containing polyketides exhibiting potent antitumor and antimicrobial activities were encoded via conserved module blocks in various strains that favor the genomic mining of these family compounds. The bioinformatic analysis of the genome of Burkholderia gladioli ATCC 10248 showed a silent trans-AT PKS biosynthetic gene cluster (BGC) on chromosome 2 (Chr2C8), which was predicted to produce new glutarimide-containing derivatives. Then, the silent polyketide synthase gene cluster was successfully activated via in situ promoter insertion and heterologous expression. As a result, seven glutarimide-containing analogs, including five new ones, gladiofungins D-H (37), and two known gladiofungin A/gladiostatin (1) and 2 (named gladiofungin C), were isolated from the fermentation of the activated mutant. Their structures were elucidated through the analysis of HR-ESI-MS and NMR spectroscopy. The structural diversities of gladiofungins may be due to the degradation of the butenolide group in gladiofungin A (1) during the fermentation and extraction process. Bioactivity screening showed that 2 and 4 had moderate anti-inflammatory activities. Thus, genome mining combined with promoter engineering and heterologous expression were proved to be effective strategies for the pathway-specific activation of the silent BGCs for the directional discovery of new natural products. Full article
(This article belongs to the Special Issue Discovery and Research of Novel Bioactive Natural Compounds)
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