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Table 1 Summary of recently discovered methyltransferases

From: Biotechnological applications of S-adenosyl-methionine-dependent methyltransferases for natural products biosynthesis and diversification

Product Enzyme Name Reaction type Natural host Gene cluster/biosynthetic pathway Discovery method Promiscuity Refs.
Novel methyltransferases discovery
 Nonamycin I NcmP Carboxylate O-methyltransferase Methylation Saccharothrix syringae NRRL B-16468 Tetramic acid, nocamycin biosynthetic cluster Biosynthetic gene cluster identification. mutant strain with NcmP disruption by λ-RED recombination Specific methylation site, methylate the pathway intermediates Mo et al. (2017)
 Antibiotic CC1065 C10P Raidcal SAM enzyme Radical generation and methylation Shewanella woodyi ATCC 51908 Spirocyclopropylcyclohexadienone biosynthesis cluster Benzodipyrrole Biosynthetic gene cluster identification. Gene inactivation and re-introduce the same gene, and intermediate characterization N.A Jin et al. (2018)
C10Q Methyltransferase Methylation and cyclization S. Zelensis nrrl 11183 N.A
 Xantholipin XanM1 O-methyltransferase Methylation Streptomyces flavogriseus Aromatic polyketides, Polycyclic xanthones biosynthetic cluster Biosynthetic gene cluster identification. In vivo gene deletion study N.A Kong et al. (2020)
XanM2 O-methyltransferase Methylation Specific methylation site, methylate the pathway intermediates
XanM3 O-methyltransferase Methylation
 Gentamicin C GenN N-methyltransferase Methylation Micromonospora echinospora Aminoglycosides, Gentamicin C biosynthesis cluster Biosynthetic cluster identification. Systematic deletion of the methyltransferase genes. knockout the biosynthetic gene cluster and complement with plasmids containing the MT genes one by one and perform in vivo biotransformation Specific methylation site, methylate the pathway intermediates Li et al. (2018)
GenD1 C-methyltransferase Methylation
GenK C-methyltransferase Methylation
GenL Terminal 6′-N-methyltransferase Methylation Outside the gentamicin C biosynthetic cluster Genome sequencing. BLAST search. Enzyme screening to identify genL. Gene deletion to confirm in vivo activity. In vitro enzyme characterization
 Pre-sodorifen pyrophosphate SodC C-methyltransferase Methylation and cyclization Serratia plymuthica WS3236 Sodorifen biosynthetic gene cluster Genome sequencing. In silico methods (antiSMASH and ClusterFinder) to identify the biosynthetic gene cluster. Overexpress the gene cluster in E. coli N.A Duell et al. (2019)
 C6,C7 prenyl pyrophosphate IPPMT Isoprenyl pyrophosphate methyltransferase Methylation Streptomyces monomycini Terpenoids biosynthetic cluster BLAST GPPMT with genome sequences of S. monomycini. Overexpression and purification from E. coli for activity characterization Multiple methylation Drummond et al. (2019)
 Teleocidin B TleD C-methyltransferase Methylation and cyclization Streptomyces mediocidicus Indole alkaloid, Teleocidin B biosynthesis cluster BLAST search to identify teleocidin B biosynthesis cluster. overexpress the gene cluster in Streptomyces lividans TK21 Produce a mixture of isomers Awakawa et al. (2014)
Promiscuous methyltransferase applications
 Vanillin COMT Caffeic acid O-methyltransferase Methylation Homo sapiens Escherichia coli Natural substrate is caffeic acid   Kunjapur et al. (2016)
 Pterostilbene COMT Arabidopsis thaliana   Heo et al. (2017)
 Fatty acid methyl esters DmJHAMT Juvenile hormone acid O-methyltransferase Methylation Drosophila melanogaster Juvenile hormone biosynthesis Homolog, sequence alignment Broad specificity for medium chain free fatty acids Sherkhanov et al. (2016)