Journal
ACS CHEMICAL BIOLOGY
Volume 11, Issue 4, Pages 943-952Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acschembio.5b00984
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Funding
- NSFC [31500638, 31470204, 81561148012, 31125001, 31290233]
- NSFC-Shandong Joint Fund for Marine Science Research Centers [U1406402]
- Special Fund for Marine Scientific Research in the Public Interest of China [201405038]
- Chinese Academy of Sciences [XDA11030403, KGZD-EW-606]
- Administration of Ocean and Fisheries of Guangdong Province [GD2012-D01-002]
- PhD Start-up Fund of Natural Science Foundation of Guangdong Province, China [2014A030310356]
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Caerulomycin A (CRM A 1) belongs to a family of natural products containing a 2,2'-bipyridyl ring core structure and is currently under development as a potent novel immunosuppressive agent. Herein, we report the functional characterization, kinetic analysis, substrate specificity, and structure insights of an aminotransferase CrmG in 1 biosynthesis. The aminotransferase CrmG was confirmed to catalyze a key transamination reaction to convert an aldehyde group to an amino group in the 1 biosynthetic pathway, preferring L-glutamate and L-glutamine as the amino donor substrates. The crystal structures of CrmG in complex with the cofactor 5'-pyridoxal phosphate (PLP) or 5'-pyridoxamine phosphate (PMP) or the acceptor substrate were determined to adopt a canonical fold-type I of PLP-dependent enzymes with a unique small additional domain. The structure guided site-directed mutagenesis identified key amino acid residues for substrate binding and catalytic activities, thus providing insights into the transamination mechanism of CrmG.
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