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Sunday, 05 November 2017 16:43

Studying Sizeable Special Synthetases - BacterioFiles 316

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Published in Bacteriofiles

This episode: Scientists study how fungi make interesting peptides using large proteins instead of ribosomes.

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(8.7 MB, 9.5 minutes)

Show notes: 

bf316beauvericinMicrobe of the episode: Nerine virus X

News item

Journal Paper:
Yu D, Xu F, Zhang S, Zhan J. 2017. Decoding and reprogramming fungal iterative nonribosomal peptide synthetases. Nat Commun 8:ncomms15349.

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Episode outline:

  • Background: Fungi often pretty weird (see ep 279)
    • Challenge many things we think are universal about life
  • One thing like that is Central Dogma
    • DNA transcribed to RNA, then that translated to protein by ribosomes
      • Genetic code and codons that code for amino acids that ribosomes assemble into chain
    • Though some viruses start from RNA, and some reverse process, etc
  • But some fungi defy dogma in another way: non-ribosomal peptides or NRPs
    • Put together amino acids into small chains/rings with non-ribosomal peptide synthetases
      • NRPSs
    • Variety of effects from resulting molecules; one is penicillin
    • Some other antibacterial or function as anti-cancer or insecticidal
    • Bacteria have NRPs too
  • So lots of interesting biochemistry and potential usefulness
    • Interest in producing compounds more easily/cheaply
  • What’s new: Now, scientists publishing in Nature Communications have studied these enzymes to understand how they work, and possibly how to modify them to produce different useful products!
  • In fungus: Beauveria bassiana
    • Produces beauvericin and bassianolide
    • Rather pretty chemical structures, lacey rings, at least drawn flat
  • NRPSs are big enzymes with multiple domains, like assembly line
    • Product gets modified in one then passed to next, etc
  • But overall function not well understood
  • Methods: First took synthetase genes and expressed in Saccharomyces cerevisiae
    • Not too easy, they’re gigantic; hard to PCR, hard to synthesize
    • Purified and tested
    • Given right substrates, produced correct product
  • Mutated single aminos of proteins to see how product changed
    • Figure out which model of process was correct
      • moving from one domain to other or building on one
    • Some domains apparently redundant; protein can still produce if one or other is removed
      • Tho removing one reduces production a lot more than other
    • Conclusion is that the moving between domains model is more likely
    • One mystery maybe solved
  • Another is what another kind of domain does
    • Produced it in isolated form and observed what it did to substrate
      • Created certain kind of bond
    • Or removed from rest of protein and observed what resulted
      • Some resulted in no protein at all; required for production
  • Also tried creating chimera enzymes of 2 synthetases
    • Created new products different from either enzyme
    • Similar in monomer structure to one but similar in length to other
    • Thus discovered which section determines length
  • Summary: Broke down functions of different sections of fungal enzymes producing useful compounds
  • Applications and implications: Easier/cheaper to produce various useful compounds
    • Medications, etc
      • Some already produced are interesting; others could be designed
    • Pretty difficult to produce synthetically
  • What do I think: Interesting to have peptides not put together by ribosome
    • But makes sense, no reason why not
    • Wonder how synthetases evolved
  • Good to understand how enzymes work in general; more potential for design
Last modified on Sunday, 05 November 2017 17:08
Jesse Noar

Jesse Noar is microbiologist with a PhD from North Carolina State University and Bachelor's from Cornell. Most of his research has focused on the amazing abilities and potential uses of bacteria, especially those found in soil. Jesse hosts the BacterioFiles podcast highlighting the most interesting recent microbiology research on all kinds of different microbes, part of the ASM family of podcasts. Learn more at asm.org/bacteriofiles or at www.bacteriofiles.com.

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