Total mycosynthesis

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Total mycosynthesis [1] is the combination of the use of a filamentous fungal host organism with a genetic expression system that allows the assembly and controlled expression of one or more biosynthetic genes. Total mycosynthesis involves the reconstruction and/or engineering of biosynthetic pathways for the production of secondary metabolites. It is competitive with chemical total synthesis. It can be used both for the production of known natural products, and for the engineering of pathways to produce new compounds or pathway intermediates.

Total MycoSynthesis and Engineering of the Fungal Metabolite Tenellin Tenellin Mycosynthesis.png
Total MycoSynthesis and Engineering of the Fungal Metabolite Tenellin

Examples include the total mycosynthesis of tenellin [2] where the tenS, tenC, tenA and tenB genes were transferred from Beauveria bassiana to the expression host Aspergillus oryzae . The expression system allows the engineering of TenS to control chain-length and methylation pattern. [3] [4]

Examples

MetaboliteYearGroupHostStep CountTitre mg/LReference
Citridone B2020Watanabe

Tang

A. nidulans60.6 https://doi.org/10.1002/anie.202008321
Monacolin J 2022WangA. niger3143 https://doi.org/10.3390/jof8040407
Tenellin2010Cox

Lazarus

A. oryzae3200 https://doi.org/10.1002/cbic.201000259
Aurovertin B2016CCC WangA. nidulans7nd https://doi.org/10.1021/acs.orglett.6b00299
Anditomin2014AbeA. oryzae135 https://doi.org/10.1021/ja508127q
Xenovulene A2018CoxA. oryzae90.5 https://doi.org/10.1038/s41467-018-04364-9

References

  1. Kahlert, Lukas; Schotte, Carsten; Cox, Russell J. (July 2021). "Total Mycosynthesis: Rational Bioconstruction and Bioengineering of Fungal Natural Products" . Synthesis. 53 (14): 2381–2394. doi:10.1055/a-1401-2716. ISSN   0039-7881. S2CID   233967389.
  2. Heneghan, Mary N.; Yakasai, Ahmed A.; Halo, Laura M.; Song, Zhongshu; Bailey, Andrew M.; Simpson, Thomas J.; Cox, Russell J.; Lazarus, Colin M. (2010-06-23). "First Heterologous Reconstruction of a Complete Functional Fungal Biosynthetic Multigene Cluster" . ChemBioChem. 11 (11): 1508–1512. doi:10.1002/cbic.201000259. PMID   20575135. S2CID   45670640.
  3. Fisch, Katja M.; Bakeer, Walid; Yakasai, Ahmed A.; Song, Zhongshu; Pedrick, Jennifer; Wasil, Zahida; Bailey, Andrew M.; Lazarus, Colin M.; Simpson, Thomas J. (2011-09-26). "Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite" . Journal of the American Chemical Society. 133 (41): 16635–16641. doi:10.1021/ja206914q. PMID   21899331 . Retrieved 2021-07-09.
  4. Yang, Xiao-Long; Friedrich, Steffen; Yin, Sen; Piech, Oliver; Williams, Katherine; Simpson, Thomas J.; Cox, Russell J. (2019). "Molecular basis of methylation and chain-length programming in a fungal iterative highly reducing polyketide synthase". Chemical Science. 10 (36): 8478–8489. doi:10.1039/C9SC03173A. ISSN   2041-6520. PMC   6839510 . PMID   31803427.