The mildiomycin biosynthesis: initial steps for sequential generation of 5-hydroxymethylcytidine 5'-monophosphate and 5-hydroxymethylcytosine in Streptoverticillium rimofaciens ZJU5119

Chembiochem : a European Journal of Chemical Biology
Li LiZixin Deng

Abstract

Mildiomycin (MIL) is a peptidyl nucleoside antibiotic with strong activity against powdery mildew disease of plants. We have cloned the MIL biosynthetic gene cluster in Streptoverticillum rimofaciens ZJU5119 and shown that this organism also produces the related antifungal compound, deshydroxymethyl mildiomycin (dHM-MIL). A cosmid genomic library was screened for a putative nucleotide hydrolase gene that is related to blsM from the blasticidin S cluster. Six cosmids were identified that contained a 3.5 kb DNA fragment that harbors a homologue of blsM. The sequence of the fragment revealed two open-reading frames that are likely to function in MIL formation: milA is a CMP hydroxymethylase gene and milB is the homologue of the CMP hydrolase gene blsM. Insertional disruption of milA abolished the production of MIL but not dHM-MIL, whereas a milB knockout strain did not produce either of the peptidyl nucleosides. Recombinant MilA was produced in E. coli and shown to specifically introduce a C-5 hydroxymethyl group on CMP, but it did not accept cytosine or dCMP as a substrate. MilB was also expressed and purified from E. coli and shown to efficiently hydrolyze both hydroxymethyl-CMP (HMCMP) and could accept CMP as an alternative sub...Continue Reading

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Citations

May 30, 2009·The Journal of Antibiotics·Masanori FunabashiSteven G Van Lanen
Apr 17, 2012·Applied and Environmental Microbiology·Li ChenMeifeng Tao
Jan 26, 2013·Chemical Society Reviews·Chia-I LinHung-wen Liu
Jul 11, 2014·International Journal of Molecular Sciences·Feng-Hui SunHong Tan
Jul 15, 2015·Journal of Industrial Microbiology & Biotechnology·Wenqing ChenZixin Deng
Feb 5, 2011·Metabolic Engineering·Jine LiHuarong Tan
Dec 4, 2014·Trends in Microbiology·Guoqing Niu, Huarong Tan
Sep 23, 2014·Applied and Environmental Microbiology·Tingli BaiMeifeng Tao
Aug 9, 2017·Science China. Life Sciences·Guoqing NiuHuarong Tan
Dec 27, 2019·Protein Science : a Publication of the Protein Society·Minhee KangZhengrong Wu
Nov 18, 2018·Journal of Industrial Microbiology & Biotechnology·Min Xu, Gerard D Wright
Jun 8, 2021·Chemical Science·Zi Fei XuHui Ming Ge
May 11, 2013·Biochemistry·Megan D SikowitzSteven E Ealick
Sep 6, 2019·ACS Synthetic Biology·Weixin TaoYuhui Sun

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