PDBsum entry 4xrt

Lyase

PDB id: 4xrt

Contents

Protein chains

302 a.a.

Ligands

FMT ×2

Waters ×635

PDB id:

4xrt

Name:

Lyase

Title:

Crystal structure of the di-domain aro/cyc stfq from the steffimycin biosynthetic pathway

Structure:

Stfq aromatase/cyclase. Chain: a, b. Engineered: yes

Source:

Streptomyces steffisburgensis. Organism_taxid: 68271. Gene: stfq. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.95Å R-factor: 0.179 R-free: 0.209

Authors:

S.C.Tsai,G.M.Caldara-Festin,D.R.Jackson,S.Aguilar,A.Patel,M.Nguyen, E.Sasaki,T.R.Valentic,J.F.Barajas,M.Vo,A.Khanna,H.-W.Liu

Key ref:

G.Caldara-Festin et al. (2015). Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases. Proc Natl Acad Sci U S A, 112, E6844. PubMed id: 26631750 DOI: 10.1073/pnas.1512976112

Date:

21-Jan-15 Release date: 02-Dec-15

Protein chains

Q2PA00  (Q2PA00_9ACTN) -  Aromatase from Streptomyces steffisburgensis

Seq: 309 a.a.

Struc: 302 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1073/pnas.1512976112

Proc Natl Acad Sci U S A 112:E6844 (2015)

PubMed id: 26631750

Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases.

G.Caldara-Festin, D.R.Jackson, J.F.Barajas, T.R.Valentic, A.B.Patel, S.Aguilar, M.Nguyen, M.Vo, A.Khanna, E.Sasaki, H.W.Liu, S.C.Tsai.

ABSTRACT

Aromatic polyketides make up a large class of natural products with diverse bioactivity. During biosynthesis, linear poly-β-ketone intermediates are regiospecifically cyclized, yielding molecules with defined cyclization patterns that are crucial for polyketide bioactivity. The aromatase/cyclases (ARO/CYCs) are responsible for regiospecific cyclization of bacterial polyketides. The two most common cyclization patterns are C7-C12 and C9-C14 cyclizations. We have previously characterized three monodomain ARO/CYCs: ZhuI, TcmN, and WhiE. The last remaining uncharacterized class of ARO/CYCs is the di-domain ARO/CYCs, which catalyze C7-C12 cyclization and/or aromatization. Di-domain ARO/CYCs can further be separated into two subclasses: "nonreducing" ARO/CYCs, which act on nonreduced poly-β-ketones, and "reducing" ARO/CYCs, which act on cyclized C9 reduced poly-β-ketones. For years, the functional role of each domain in cyclization and aromatization for di-domain ARO/CYCs has remained a mystery. Here we present what is to our knowledge the first structural and functional analysis, along with an in-depth comparison, of the nonreducing (StfQ) and reducing (BexL) di-domain ARO/CYCs. This work completes the structural and functional characterization of mono- and di-domain ARO/CYCs in bacterial type II polyketide synthases and lays the groundwork for engineered biosynthesis of new bioactive polyketides.