4XRT

Crystal structure of the di-domain ARO/CYC StfQ from the steffimycin biosynthetic pathway

Summary for 4XRT

• Entry DOI: 10.2210/pdb4xrt/pdb
• Related: 2KF2 2RER 2REZ 3TFZ 4XRW
• Descriptor: StfQ Aromatase/Cyclase, FORMIC ACID (3 entities in total)
• Functional Keywords: aromatase/cyclase, helix-grip fold, polyketide, polyketide synthase, natural products, dehydratase, aro/cyc, lyase
• Biological source: Streptomyces steffisburgensis
• Total number of polymer chains: 2
• Total formula weight: 74315.26

Authors

Tsai, S.C.,Caldara-Festin, G.M.,Jackson, D.R.,Aguilar, S.,Patel, A.,Nguyen, M.,Sasaki, E.,Valentic, T.R.,Barajas, J.F.,Vo, M.,Khanna, A.,Liu, H.-W. (deposition date: 2015-01-21, release date: 2015-12-02, Last modification date: 2024-02-28)

Primary citation

Caldara-Festin, G.,Jackson, D.R.,Barajas, J.F.,Valentic, T.R.,Patel, A.B.,Aguilar, S.,Nguyen, M.,Vo, M.,Khanna, A.,Sasaki, E.,Liu, H.W.,Tsai, S.C.
Structural and functional analysis of two di-domain aromatase/cyclases from type II polyketide synthases.
Proc.Natl.Acad.Sci.USA, 112:E6844-E6851, 2015

PubMed 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.

PubMed: 26631750
DOI: 10.1073/pnas.1512976112

Experimental method

X-RAY DIFFRACTION (1.952 Å)