Biosynthesis of the anti-infective marformycins featuring pre-NRPS assembly line N-formylation and O-methylation and post-assembly line C-hydroxylation chemistries.
The biosynthetic gene cluster governing production of anti-infective marformycins was identified from deep sea-derived Streptomyces drozdowiczii SCSIO 10141. The putative mfn gene cluster (45 kb, 20 orfs) was found to encode six NRPSs and related proteins for cyclodepsipeptide core construction (mfnCDEFKL), a methionyl-tRNA formyltransferase (mfnA), a SAM-dependent methyltransferase (mfnG), and a cytochrome P450 monooxygenase for piperazic acid moiety hydroxylation (mfnN); notably, only MfnN uses an intact cyclodepsipeptide intermediate as its substrate.
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Jing
J
Liu
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Bo
B
Wang
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Hongzhi
H
Li
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Yunchang
Y
Xie
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Qinglian
Q
Li
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Xiangjing
X
Qin
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Xing
X
Zhang
CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301, China.
Jianhua
J
Ju
D000890:Anti-Infective Agents / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D047630:Depsipeptides / Q000737:chemistry*; D006900:Hydroxylation; D019877:Hydroxymethyl and Formyl Transferases / Q000378:metabolism; D008386:Marine Biology; D008745:Methylation; D015394:Molecular Structure; D005810:Multigene Family; D010453:Peptide Synthases / Q000378:metabolism*; D013302:Streptomyces / Q000737:chemistry* / Q000235:genetics
D000890:Anti-Infective Agents; D047630:Depsipeptides; D003577:Cytochrome P-450 Enzyme System; D019877:Hydroxymethyl and Formyl Transferases; C021561:methionyl-tRNA formyltransferase; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase