5LVW

XiaF (FADH2) from Streptomyces sp.

Summary for 5LVW

• Entry DOI: 10.2210/pdb5lvw/pdb
• Related: 2JBR
• Descriptor: XiaF protein, FLAVIN-ADENINE DINUCLEOTIDE, INDOLE, ... (5 entities in total)
• Functional Keywords: detoxification, non-canonical flavin-dependent terpenoid cyclase, xenobiotics-degrading enzyme, indigo, indirubin, oxidoreductase
• Biological source: Streptomyces sp.
• Total number of polymer chains: 1
• Total formula weight: 45238.51

Authors

Kugel, S.,Baunach, M.,Baer, P.,Ishida-Ito, M.,Sundaram, S.,Xu, Z.,Groll, M.,Hertweck, C. (deposition date: 2016-09-14, release date: 2017-06-28, Last modification date: 2024-01-17)

Primary citation

Kugel, S.,Baunach, M.,Baer, P.,Ishida-Ito, M.,Sundaram, S.,Xu, Z.,Groll, M.,Hertweck, C.
Cryptic indole hydroxylation by a non-canonical terpenoid cyclase parallels bacterial xenobiotic detoxification.
Nat Commun, 8:15804-15804, 2017

PubMed Abstract: Terpenoid natural products comprise a wide range of molecular architectures that typically result from C-C bond formations catalysed by classical type I/II terpene cyclases. However, the molecular diversity of biologically active terpenoids is substantially increased by fully unrelated, non-canonical terpenoid cyclases. Their evolutionary origin has remained enigmatic. Here we report the in vitro reconstitution of an unusual flavin-dependent bacterial indoloterpenoid cyclase, XiaF, together with a designated flavoenzyme-reductase (XiaP) that mediates a key step in xiamycin biosynthesis. The crystal structure of XiaF with bound FADH (at 2.4 Å resolution) and phylogenetic analyses reveal that XiaF is, surprisingly, most closely related to xenobiotic-degrading enzymes. Biotransformation assays show that XiaF is a designated indole hydroxylase that can be used for the production of indigo and indirubin. We unveil a cryptic hydroxylation step that sets the basis for terpenoid cyclization and suggest that the cyclase has evolved from xenobiotics detoxification enzymes.

PubMed: 28643772
DOI: 10.1038/ncomms15804

Experimental method

X-RAY DIFFRACTION (2.9 Å)