Module description#

The nrps_pks_domains module annotates domains with poly keytide synthase (PKS) and non-ribosomal peptide synthase (NRPS) related functions.

Annotated domains#

Domain name Icon Description Source
ACP Acyl-carrier protein domain Medema et al. 2011
ACP_beta Beta-branching acyl-carrier protein domain SMART
ACPS 4'-phosphopantetheinyl transferase Pfam
Aminotran_1_2 Aminotransferase class I and II Pfam
Aminotran_3 Aminotransferase class III Pfam
Aminotran_4 Aminotransferase class IV Pfam
Aminotran_5 Aminotransferase class V Pfam
AMP-binding A Adenylation domain Pfam
A-OX A Adenylation domain with integrated oxidase Medema et al. 2011
B B Branching domain Blin et al. 2017
Beta_elim_lyase SH Beta-eliminating lyase Pfam
CAL_domain CAL Co-enzyme A ligase domain Medema et al. 2011
cAT cAT Choline/Carnitine o-acyltransferase Pfam
Cglyc C Glycopeptide condensation domain Medema et al. 2011
cMT cMT Carbon methyltransferase Ansari et al. 2008
Condensation C Condensation domain Pfam
Condensation_DCL C Condensation domain linking a L-amino acid to a peptide ending with a D-amino acid Rausch et al. 2007
Condensation_Dual C Dual condensation/epimerisation domain Rausch et al. 2007
Condensation_LCL C Condensation domain linking a L-amino acid to a peptide ending with a L-amino acid Rausch et al. 2007
Condensation_Starter C Starter condensation domain Rausch et al. 2007
ECH ECH Enoyl-CoA hydratase/isomerase Pfam
Ene_KS KS Enediyine ketosynthase Yadav et al. 2009
Epimerization domain E Epimerization domain Weber et al. 2009
F F Formylation domain Blin et al. 2017
FkbH FkbH FkbH-like domain Blin et al. 2017
GNAT GNAT GNAT domain Blin et al. 2017
Hal Hal Halogenase domain Blin et al. 2017
Heterocyclization C Heterocyclization domain Medema et al. 2011
Hyb_KS KS Hybrid ketosynthase Yadav et al. 2009
Itr_KS KS Iterative ketosynthase Yadav et al. 2009
LPG_synthase_C Phosphatidylglycerol lysyltransferase, C-terminal Pfam
Mod_KS KS Modular ketosynthase Yadav et al. 2009
NAD_binding_4 NAD Male sterility protein Pfam
nMT nMT Nitrogen methyltransferase Ansari et al. 2008
NRPS-COM_Cterm NRPS COM domain C-terminal Medema et al. 2011
NRPS-COM_Nterm NRPS COM domain N-terminal Medema et al. 2011
oMT oMT Oxygen methyltransferase Ansari et al. 2008
PCP Peptidyl-carrier protein domain Medema et al. 2011
PKS_AT AT Acyltransferase domain SMART
PKS_DH DH Dehydratase domain SMART
PKS_DH2 DH Dehydratase domain (avoids false positive PS domains)
PKS_DHt DHt Dehydratase domain variant more commonly found in trans-AT PKS clusters
PKS_Docking_Cterm PKS C-terminal docking domain Medema et al. 2011
PKS_Docking_Nterm PKS N-terminal docking domain Medema et al. 2011
PKS_ER ER Enoylreductase domain SMART
PKS_KR KR Ketoreductase domain SMART
PKS_KS KS Ketosynthase domain SMART
PKS_PP Phosphopantetheine acyl carrier protein group (new in 5.1.1) SMART
Polyketide_cyc2 Polyketide cyclase/dehydratase Pfam
Polyketide_cyc Polyketide cyclase Pfam
PS PS Pyran synthase domain Blin et al. 2017
PT PT Product template domain TIGRFams
SAT SAT Starter unit:ACP transacylase in aflatoxin biosynthesis Pfam
TD TD Terminal reductase domain Medema et al. 2011
Thioesterase TE Thioesterase domain Pfam
TIGR01720 NRPS domain of unknown function TIGRFams
TIGR02353 NRPS terminal domain of unknown function TIGRFams
Tra_KS KS Trans-acyltransferase ketosynthase Yadav et al. 2009
Trans-AT_docking Trans-acyltransferase docking domain Medema et al. 2011
X X Glycopeptide-specific NRPS domain responsible for oxygenase recruitment Medema et al. 2011

Trans-AT domain subtypes#

Ketosynthase domains (KS) of trans-acyltransferase polyketide synthases (Trans-AT-PKS) have additional to their substrate specificities, i.e., the monomer incorporated into the module before the KS.

Canonical double bonds are located between the alpha and beta position.

Two modes of shifted double bond formation have been described, including a dedicated module for double bond shift and the presence of a characteristic DH-like domain. KS domains with substrate specificities for shifted double bonds usually group with KS domains that show substrate specificity for completely reduced moieties.

Domains predicted to be non-elongating will have a prefix of non-elongating- within antiSMASH. Ambiguous results between categories will be separated by a /, e.g. beta-OH/keto.

All the following categories are predicted by profiles from TransATor (Helfrich et. al. 2019).

Name Specificity
AA Glycine introduced by the NRPS module upstream.
AcST Acetyl groups as the starting building block of the polyketide.
alpha-D-Me-shDB Alpha-methyl groups with beta-gamma-double bonds.
alphabeta-OH Alpha-hydroxyl groups in conjunction with beta-hydroxyl groups.
alphaMe Alpha-methyl groups with either a reduced bond or a beta-gamma-double bond.
alphaMe-beta-D-OH Alpha-L-methyl groups in conjunction with beta-D-hydroxyl groups.
alphaMe-beta-L-OH Alpha-methyl groups in conjunction with beta-L-hydroxyl groups.
alphaMe-betaOH Alpha-methyl groups in conjunction with beta-hydroxyl groups.
alphaMe-DB Alpha-methyl groups with double bonds.
alphaMe-eDB Alpha-methyl groups with E-configured double bonds.
alphaMe-zDB Alpha-methyl groups with Z-configured double bonds
arST Aromatic rings as the starting building block of the polyketide.
beta-D-OH Beta-D-hydroxyl groups.
beta-D-OMe Beta-methoxy groups.
beta-Me Either beta-exomethylene groups or reduced beta-methyl groups, depending on the module composition upstream.
beta-MeDB Beta-methyl groups with E-configured double bonds.
beta-L-OH Beta-L-hydroxyl groups.
beta-OH Beta-hydroxyl groups.
br This type is specific for vinylogous chain branching.
DB Double bonds of various configurations.
eDB E-configured double bonds.
keto Beta-keto groups.
lacST Lactate as the starting building block of the polyketide.
MeOST Methoxycarbonyl units as the starting building block of the polyketide.
Miscellaneous This type is elongating, but the substrate specificity can not be predicted.
non-elongating When without a suffix, this type is non-elongating, but the substrate specificity can not be predicted.
OUT This type is in an out group.
Oxa Amino acids containing oxazole or thiazole rings introduced by the NRPS module upstream.
OxI Substrates with inserted oxygen, oftentimes resulting in oxidative cleaving.
pyr Pyran or furan rings, depending on the presence of an in-trans-acting hydroxylases two modules upstream.
red Reduced bonds.
shDB Beta-gamma-double bonds.
ST Amidated amino acid starters. Amide groups are introduced by a dedicated aminotransferase.
unST Phosphoglycerate-derived molecules as the starting building block of the polyketide.
zDB Z-configured double bonds.

1. Rausch, C., Hoof, I., Weber, T., Wohlleben, W. and Huson, D.H. (2007) Phylogenetic analysis of condensation domains in NRPS sheds light on their functional evolution. BMC Evol. Biol., vol. 7, 78.

2. Medema, M.H., Blin, K., Cimermancic, P., de Jager, V., Zakrzewski, P., Fischbach, M.A., Weber, T., Takano, E., and Breitling, R. (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucl. Acids Research, vol. 39, W339-W346.

3. Weber, T., Rausch, C., Lopez, P., Hoof, I., Gaykova, V., Huson, DH., Wohlleben, W. (2009) CLUSEAN: a computer-based framework for the automated analysis of bacterial secondary metabolite biosynthetic gene clusters. J. Biotechnol., vol. 140 13-17.

4. Yadav, G., Gokhale, R.S. and Mohanty, D. (2009) Towards prediction of metabolic products of polyketide synthases: an in silico analysis. PLoS Comput. Biol., vol. 5, e1000351.

5. Blin,K., Wolf,T., Chevrette,M.G., Lu,X., Schwalen,C.J., Kautsar,S.A., Suarez Duran,H.G., de Los Santos,E.L.C., Kim,H.U., Nave,M., et al. (2017) antiSMASH 4.0-improvements in chemistry prediction and gene cluster boundary identification. Nucleic Acids Res., vol. 45, W36–W41.

6. Ansari, M.Z., Sharma, J., Gokhale, R.S. and Mohanty, D. (2008) In silico analysis of methyltransferase domains involved in biosynthesis of secondary metabolites. BMC Bioinformatics, vol. 9, 454

7. Helfrich, E.J.N., Ueoka, R., Dolev, A., Rust, M., Meoded, R.A., Bhushan, A., Califano, G., Costa, R., Gugger, M., Steinbeck, C., Moreno, P., Piel, J. (2019) Automated structure prediction of trans-acyltransferase polyketide synthase products. Nat. Chem. Biol., vol. 15, 813–821.