期刊
NATURE CHEMICAL BIOLOGY
卷 18, 期 6, 页码 652-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41589-022-01013-7
关键词
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资金
- Marie Sklodowska-Curie Actions Individual Fellowship [745435]
- DBU (Deutsche Bundesstiftung Umwelt) [20015/400]
- CSC (China Scholarship Council)
- German Research Foundation [DFG GU 1233/1-1, DFG GU 1134/3-1]
- Marie Curie Actions (MSCA) [745435] Funding Source: Marie Curie Actions (MSCA)
This study elucidates the biosynthetic process of furanolide assembly, providing insights into the function and mechanism of key enzymes. It expands the biocatalytic toolbox for gamma-butyrolactone formation and lays the foundation for targeted discovery and enzymatic synthesis of furanolides.
The gamma-butyrolactone motif is found in many natural signaling molecules and other specialized metabolites. A prominent example is the potent aquatic phytotoxin cyanobacterin, which has a highly functionalized gamma-butyrolactone core structure. The enzymatic machinery that assembles cyanobacterin and structurally related natural products (herein termed furanolides) has remained elusive for decades. Here, we elucidate the biosynthetic process of furanolide assembly. The cyanobacterin biosynthetic gene cluster was identified by targeted bioinformatic screening and validated by heterologous expression in Escherichia coli. Full functional evaluation of the recombinant key enzymes in vivo and in vitro, individually and in concert, provided in-depth mechanistic insights into a streamlined C-C bond-forming cascade that involves installation of compatible reactivity at seemingly unreactive C alpha positions of amino acid precursors. Our work extends the biosynthetic and biocatalytic toolbox for gamma-butyrolactone formation, provides a general paradigm for furanolide biosynthesis and sets the stage for their targeted discovery, biosynthetic engineering and enzymatic synthesis.
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