Bilin-dependent regulation of chlorophyll biosynthesis by GUN4

Weiqing Zhang, Robert D. Willows, Rui Deng, Zheng Li, Mengqi Li, Yan Wang, Yunling Guo, Weida Shi, Qiuling Fan, Shelley S. Martin, Nathan C. Rockwell, J. Clark Lagarias*, Deqiang Duanmu*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    4 Citations (Scopus)


    Biosyntheses of chlorophyll and heme in oxygenic phototrophs share a common trunk pathway that diverges with insertion of magnesium or iron into the last common intermediate, protoporphyrin IX. Since both tetrapyrroles are pro-oxidants, it is essential that their metabolism is tightly regulated. Here, we establish that heme-derived linear tetrapyrroles (bilins) function to stimulate the enzymatic activity of magnesium chelatase (MgCh) via their interaction with GENOMES UNCOUPLED 4 (GUN4) in the model green alga Chlamydomonas reinhardtii. A key tetrapyrrole-binding component of MgCh found in all oxygenic photosynthetic species, CrGUN4, also stabilizes the bilin-dependent accumulation of protoporphyrin IX-binding CrCHLH1 subunit of MgCh in light-grown C. reinhardtii cells by preventing its photooxidative inactivation. Exogenous application of biliverdin IXα reverses the loss of CrCHLH1 in the bilin-deficient heme oxygenase (hmox1) mutant, but not in the gun4 mutant. We propose that these dual regulatory roles of GUN4: bilin complexes are responsible for the retention of bilin biosynthesis in all photosynthetic eukaryotes, which sustains chlorophyll biosynthesis in an illuminated oxic environment.

    Original languageEnglish
    Article numbere2104443118
    Pages (from-to)1-9
    Number of pages9
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Issue number20
    Publication statusPublished - 18 May 2021


    • Bilin reductase
    • Heme oxygenase
    • Photosynthesis
    • Phycocyanobilin
    • Reactive oxygen species


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