Biology:Total mycosynthesis
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.
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
| Metabolite | Year | Group | Host | Step Count | Titre mg/L | Reference |
|---|---|---|---|---|---|---|
| Citridone B | 2020 | Watanabe
Tang |
A. nidulans | 6 | 0.6 | https://doi.org/10.1002/anie.202008321 |
| Monacolin J | 2022 | Wang | A. niger | 3 | 143 | https://doi.org/10.3390/jof8040407 |
| Tenellin | 2010 | Cox
Lazarus |
A. oryzae | 3 | 200 | https://doi.org/10.1002/cbic.201000259 |
| Aurovertin B | 2016 | CCC Wang | A. nidulans | 7 | nd | https://doi.org/10.1021/acs.orglett.6b00299 |
| Anditomin | 2014 | Abe | A. oryzae | 13 | 5 | https://doi.org/10.1021/ja508127q |
| Xenovulene A | 2018 | Cox | A. oryzae | 9 | 0.5 | https://doi.org/10.1038/s41467-018-04364-9 |
References
- ↑ Kahlert, Lukas; Schotte, Carsten; Cox, Russell J. (July 2021). "Total Mycosynthesis: Rational Bioconstruction and Bioengineering of Fungal Natural Products" (in en). Synthesis 53 (14): 2381–2394. doi:10.1055/a-1401-2716. ISSN 0039-7881. http://www.thieme-connect.de/DOI/DOI?10.1055/a-1401-2716.
- ↑ 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" (in en). ChemBioChem 11 (11): 1508–1512. doi:10.1002/cbic.201000259. PMID 20575135. https://onlinelibrary.wiley.com/doi/10.1002/cbic.201000259.
- ↑ Fisch, Katja M.; Bakeer, Walid; Yakasai, Ahmed A.; Song, Zhongshu; Pedrick, Jennifer; Wasil, Zahida; Bailey, Andrew M.; Lazarus, Colin M. et al. (2011-09-26). "Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite" (in EN). Journal of the American Chemical Society 133 (41): 16635–16641. doi:10.1021/ja206914q. PMID 21899331. https://pubs.acs.org/doi/abs/10.1021/ja206914q. Retrieved 2021-07-09.
- ↑ 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" (in en). Chemical Science 10 (36): 8478–8489. doi:10.1039/C9SC03173A. ISSN 2041-6520. PMID 31803427. PMC 6839510. http://xlink.rsc.org/?DOI=C9SC03173A.
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