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TitleThe biosynthesis of the odorant 2-methylisoborneol is compartmentalized inside a protein shell.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 9715, Year 2024
Publish dateNov 9, 2024
AuthorsMichael P Andreas / Tobias W Giessen /
PubMed AbstractTerpenoids are the largest class of natural products, found across all domains of life. One of the most abundant bacterial terpenoids is the volatile odorant 2-methylisoborneol (2-MIB), partially ...Terpenoids are the largest class of natural products, found across all domains of life. One of the most abundant bacterial terpenoids is the volatile odorant 2-methylisoborneol (2-MIB), partially responsible for the earthy smell of soil and musty taste of contaminated water. Many bacterial 2-MIB biosynthetic gene clusters were thought to encode a conserved transcription factor, named EshA in the model soil bacterium Streptomyces griseus. Here, we revise the function of EshA, now referred to as Sg Enc, and show that it is a Family 2B encapsulin shell protein. Using cryo-electron microscopy, we find that Sg Enc forms an icosahedral protein shell and encapsulates 2-methylisoborneol synthase (2-MIBS) as a cargo protein. Sg Enc contains a cyclic adenosine monophosphate (cAMP) binding domain (CBD)-fold insertion and a unique metal-binding domain, both displayed on the shell exterior. We show that Sg Enc CBDs do not bind cAMP. We find that 2-MIBS cargo loading is mediated by an N-terminal disordered cargo-loading domain and that 2-MIBS activity and Sg Enc shell structure are not modulated by cAMP. Our work redefines the function of EshA and establishes Family 2B encapsulins as cargo-loaded protein nanocompartments involved in secondary metabolite biosynthesis.
External linksNat Commun / PubMed:39521781 / PubMed Central
MethodsEM (single particle)
Resolution2.71 - 3.02 Å
Structure data

44553

9bhu

EMDB-44553, PDB-9bhu:
Streptomyces griseus Family 2B encapsulin shell
Method: EM (single particle) / Resolution: 2.71 Å

44554

9bhv

EMDB-44554, PDB-9bhv:
Streptomyces griseus Family 2B encapsulin shell with 2-methylisoborneol synthase cargo
Method: EM (single particle) / Resolution: 3.02 Å

44557

9bi0

EMDB-44557, PDB-9bi0:
Streptomyces griseus Family 2B encapsulin shell with 2-methylisoborneol synthase cargo in 20 mM cAMP
Method: EM (single particle) / Resolution: 2.93 Å

Chemicals

ChemComp-CA:
Unknown entry

Source
  • streptomyces griseus subsp. griseus (bacteria)
KeywordsVIRUS LIKE PARTICLE / Encapsulin / nanocompartment

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