Structural mechanism for bacterial oxidation of oceanic trimethylamine into trimethylamine N‐oxide. Issue 6 (10th January 2017)

• Record Type: Journal Article
• Authors: Li, Chun‐Yang; Chen, Xiu‐Lan; Zhang, Dian; Wang, Peng; Sheng, Qi; Peng, Ming; Xie, Bin‐Bin; Qin, Qi‐Long; Li, Ping‐Yi; Zhang, Xi‐Ying; Su, Hai‐Nan; Song, Xiao‐Yan; Shi, Mei; Zhou, Bai‐Cheng; Xun, Lu‐Ying; Chen, Yin; Zhang, Yu‐Zhong
• Is Part Of: Molecular microbiology. Volume 103:Issue 6(2017)
• Page Start: 992
• Page End: 1003
• Publication Date: 2017-01-10
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13605
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: Trimethylamine (TMA) and trimethylamine N ‐oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin‐containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm ( Rn Tmm) and elucidated the catalytic mechanism of TMA oxidation by Rn Tmm. The catalytic process of Tmm consists of a reductive half‐reaction and an oxidative half‐reaction. In the reductive half‐reaction, FAD is reduced and a C4a‐hydroperoxyflavin intermediate forms. In the oxidative half‐reaction, this intermediate attracts TMA through electronic interactions. After TMA binding, NADP + bends and interacts with D317, shutting off the entrance to create a protected micro‐environment for catalysis and exposing C4a‐hydroperoxyflavin to TMA for oxidation. Sequence analysis suggests that the proposed catalytic mechanism is common for bacterial Tmms. These findings reveal the catalytic process of TMA oxidation by marine bacterial Tmm and first show that NADP + undergoes a conformational change in the oxidative half‐reaction of FMOs. Abstract : Trimethylamine (TMA) and trimethylamine N ‐oxide (TMAO) are widespread in the ocean. TMA monooxygenase (Tmm), a bacterial flavin‐containing monooxygenase (FMO), is responsible for converting marine TMA to TMAO. In this study, we elucidated the catalytic mechanism of TMA oxidation by a marine bacterial Tmm. The catalytic process of Tmm consists of a reductive half‐reaction and an oxidative half‐reaction. Our findings first demonstrate that NADP + undergoes a conformational change in the oxidative half‐reaction of FMOs.