Characterization of BlsM, a nucleotide hydrolase involved in cytosine production for the biosynthesis of blasticidin S

Chembiochem : a European Journal of Chemical Biology
Laura L Grochowski, T M Zabriskie

Abstract

Biosynthesis of the antifungal agent blasticidin S in Streptomyces griseochromogenes requires the formation of free cytosine. The blsM gene in the blasticidin S gene cluster is predicted to encode a protein that has sequence homology with several nucleoside transferases. In vitro analysis of recombinant BlsM revealed that the enzyme functions as a nucleotide hydrolase and catalyzes the formation of free cytosine by using cytidine 5'-monophosphate (CMP) as the preferred substrate. Cytosine production was significantly lower with CDP, CTP, and dCMP as alternate substrates. BlsM was also observed to have low-level cytidine deaminase activity, converting cytidine and deoxycytidine to uridine and deoxyuridine, respectively. Point mutations were introduced in blsM at putative catalytic residues to generate three mutant enzymes, BlsM Ser98Asp, Glu104Ala, and Glu104Asp. All three mutants lost CMP hydrolysis activity, but the Ser98Asp mutant showed a modest increase in cytidine deaminase activity.

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Citations

May 11, 2013·Biochemistry·Megan D SikowitzSteven E Ealick
Dec 4, 2014·Trends in Microbiology·Guoqing Niu, Huarong Tan
Aug 9, 2017·Science China. Life Sciences·Guoqing NiuHuarong Tan
Dec 27, 2019·Protein Science : a Publication of the Protein Society·Minhee KangZhengrong Wu
Jan 20, 2007·The Journal of Biological Chemistry·Yoan Konto GhiorghiP Alexandre Kaminski

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An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.