Genomic loci for this biosynthetic pathway

Cluster Type From To
The following clusters are from record BGC0000315.1:
Cluster 1NRP182872

BGC0000315, calcium-dependent antibiotic biosynthetic gene cluster from Streptomyces coelicolor. Locus 1. Full MIBiG entry.

Chemical compounds

Compound: CDA1b
SMILES string: Copy to clipboard
Molecular formula: C66H79N14O29P
Exact molecular mass: 1562.49 Da (M+)
Molecular activity: Antibacterial
Molecular target: Unknown

Class-specific details

Biosynthetic class(es):
NRP
Nonribosomal peptide subclass:
Ca+-dependent lipopeptide (cyclic)
2,3-epoxyhexanoyl
Thioesterase type:
Type I & II
Release / cyclization type:
Macrolactonization

Nonribosomal peptide synthetases:
SCO3230
Module 1
A specificity: Serine
Evidence for specificity: Sequence-based prediction
C domain subtype: Starter
Module 2
A specificity: Threonine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 3
A specificity: Tryptophan
Evidence for specificity: Sequence-based prediction
AA is epimerized
C domain subtype: LCL
Module 4
A specificity: Aspartate
Evidence for specificity: Sequence-based prediction
C domain subtype: DCL
Module 5
A specificity: Aspartate
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 6
A specificity: 4-Hydroxyphenylglycine
Evidence for specificity: Sequence-based prediction
AA is epimerized
C domain subtype: LCL
SCO3231
Module 7
A specificity: Aspartate
Evidence for specificity: Other
C domain subtype: DCL
Module 8
A specificity: Glycine
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL
Module 9
A specificity: Asparigine or (2S, 3S)-3-hydroxyasparagine
Evidence for specificity: Structure-based inference
AA is epimerized
C domain subtype: LCL
SCO3232
Module 10
A specificity: Glutamate or (2S, 3R)-3-methylglutamate
Evidence for specificity: Other
C domain subtype: DCL
Module 11
A specificity: Tryptophan
Evidence for specificity: Sequence-based prediction
C domain subtype: LCL

Gene cluster description

calcium-dependent antibiotic (BGC0000315). Gene Cluster 1. Biosynthetic class = NRP. GenBank AL645882. Click on genes for more information.

Legend:

biosynthetic genes
transport-related genes
regulatory genes
other genes

Domain annotation

Homologous known gene clusters

General MIBiG information on this cluster

Complete gene cluster sequence?complete
Evidence for cluster-compound connection:Knock-out studies
MIxS-compliance:Unknown
Contact for this cluster:Jason Micklefield (The University of Manchester)

Literature references

1. Hojati Z et al. (2002) Structure, biosynthetic origin, and engineered biosynthesis of calcium-dependent antibiotics from Streptomyces coelicolor. Chem Biol 9(11):1175-87.
2. Milne C et al. (2006) Biosynthesis of the (2S,3R)-3-methyl glutamate residue of nonribosomal lipopeptides. J Am Chem Soc 128(34):11250-9.
3. Mahlert C et al. (2007) Stereospecific enzymatic transformation of alpha-ketoglutarate to (2S,3R)-3-methyl glutamate during acidic lipopeptide biosynthesis. J Am Chem Soc 129(39):12011-8. Epub 2007 Sep 5.
4. Ryding NJ et al. (2002) Regulation of the Streptomyces coelicolor calcium-dependent antibiotic by absA, encoding a cluster-linked two-component system. J Bacteriol 184(3):794-805.
5. McKenzie NL, Nodwell JR. (2007) Phosphorylated AbsA2 negatively regulates antibiotic production in Streptomyces coelicolor through interactions with pathway-specific regulatory gene promoters. J Bacteriol 189(14):5284-92. Epub 2007 May 18.
6. Powell A et al. (2007) Engineered biosynthesis of nonribosomal lipopeptides with modified fatty acid side chains. J Am Chem Soc 129(49):15182-91. Epub 2007 Nov 17.
7. Uguru GC et al. (2004) Active-site modifications of adenylation domains lead to hydrolysis of upstream nonribosomal peptidyl thioester intermediates. J Am Chem Soc 126(16):5032-3.
8. Thirlway J et al. (2012) Introduction of a non-natural amino acid into a nonribosomal peptide antibiotic by modification of adenylation domain specificity. Angew Chem Int Ed Engl 51(29):7181-4. doi: 10.1002/anie.201202043.
9. Neary JM et al. (2007) An asparagine oxygenase (AsnO) and a 3-hydroxyasparaginyl phosphotransferase (HasP) are involved in the biosynthesis of calcium-dependent lipopeptide antibiotics. Microbiology 153(Pt 3):768-76.
10. Strieker M et al. (2007) Mechanistic and structural basis of stereospecific Cbeta-hydroxylation in calcium-dependent antibiotic, a daptomycin-type lipopeptide. ACS Chem Biol 2(3):187-96.
11. Kopp F et al. (2008) Harnessing the chemical activation inherent to carrier protein-bound thioesters for the characterization of lipopeptide fatty acid tailoring enzymes. J Am Chem Soc 130(8):2656-66. doi: 10.1021/ja078081n. Epub 2008 Feb
12. Powell A et al. (2007) Engineered biosynthesis of nonribosomal lipopeptides with modified fatty acid side chains. J Am Chem Soc 129(49):15182-91. Epub 2007 Nov 17.
13. Lewis RA et al. (2011) Active site modification of the beta-ketoacyl-ACP synthase FabF3 of Streptomyces coelicolor affects the fatty acid chain length of the CDA lipopeptides. Chem Commun (Camb) 47(6):1860-2. doi: 10.1039/c0cc03444d. Epub 2010
14. Kraas FI et al. (2012) Exploring the mechanism of lipid transfer during biosynthesis of the acidic lipopeptide antibiotic CDA. FEBS Lett 586(3):283-8. doi: 10.1016/j.febslet.2012.01.003. Epub 2012