CATH Classification

Domain Context

CATH Clusters

Superfamily alpha/beta hydrolase
Functional Family Narbonolide/10-deoxymethynolide synthase PikA4, module 6

Enzyme Information

2.3.1.240
Narbonolide synthase.
based on mapping to UniProt Q9ZGI2
Malonyl-CoA + 6 (2S)-methylmalonyl-CoA + 5 NADPH = narbonolide + 7 CoA + 7 CO(2) + 5 NADP(+) + 2 H(2)O.
-!- The product, narbonolide, contains a 14-membered ring and is an intermediate in the biosynthesis of narbonomycin and pikromycin in the bacterium Streptomyces venezuelae. -!- The enzyme also produces 10-deoxymethynolide (see EC 2.3.1.239). -!- The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. -!- Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). -!- Not all active sites are used in the biosynthesis.
2.3.1.239
10-deoxymethynolide syntase.
based on mapping to UniProt Q9ZGI2
Malonyl-CoA + 5 (2S)-methylmalonyl-CoA + 5 NADPH = 10-deoxymethynolide + 6 CoA + 6 CO(2) + 5 NADP(+) + 2 H(2)O.
-!- The product, 10-deoxymethynolide, contains a 12-membered ring and is an intermediate in the biosynthesis of methymycin in the bacterium Streptomyces venezuelae. -!- The enzyme also produces narbonolide (see EC 2.3.1.240). -!- The enzyme has 29 active sites arranged in four polypeptides (pikAI - pikAIV) with a loading domain, six extension modules and a terminal thioesterase domain. -!- Each extension module contains a ketosynthase (KS), keto reductase (KR), an acyltransferase (AT) and an acyl-carrier protein (ACP). -!- Not all active sites are used in the biosynthesis.

UniProtKB Entries (1)

Q9ZGI2
PIKA4_STRVZ
Streptomyces venezuelae
Narbonolide/10-deoxymethynolide synthase PikA4, module 6

PDB Structure

PDB 2H7X
External Links
Method X-RAY DIFFRACTION
Organism Escherichia
Primary Citation
Structural and Mechanistic Insights of Polyketide Macrolactonization from Polyketide-based Affinity Labels
Giraldes, J.W., Akey, D.L., Kittendorf, J.D., Sherman, D.H., Smith, J.S., Fecik, R.A.
NAT.CHEM.BIOL.