Engineering Saccharomyces cerevisiae for production of the capsaicinoid nonivamide
(2022) In Microbial Cell Factories 21.- Abstract
- Background
Capsaicinoids are produced by plants in the Capsicum
Results
genus and are the main reason for the pungency of chili pepper fruits.
They are strong agonists of TRPV1 (the transient receptor potential
cation channel subfamily V member 1) and used as active ingredients in
pharmaceuticals for the treatment of pain. The use of bioengineered
microorganisms in a fermentation process may be an efficient route for
their preparation, as well as for the discovery of (bio-)synthetic
capsaicinoids with improved or novel bioactivities.
Saccharomyces cerevisiae was engineered to over-express a selection of amide-forming N-acyltransferase
and CoA-ligase enzyme cascades... (More) - Background
Capsaicinoids are produced by plants in the Capsicum
Results
genus and are the main reason for the pungency of chili pepper fruits.
They are strong agonists of TRPV1 (the transient receptor potential
cation channel subfamily V member 1) and used as active ingredients in
pharmaceuticals for the treatment of pain. The use of bioengineered
microorganisms in a fermentation process may be an efficient route for
their preparation, as well as for the discovery of (bio-)synthetic
capsaicinoids with improved or novel bioactivities.
Conclusions
Saccharomyces cerevisiae was engineered to over-express a selection of amide-forming N-acyltransferase
and CoA-ligase enzyme cascades using a combinatorial gene assembly
method, and was screened for nonivamide production from supplemented
vanillylamine and nonanoic acid. Data from this work demonstrate that
Tyramine N-hydroxycinnamoyl transferase from Capsicum annuum (CaAT) was most efficient for nonivamide formation in yeast, outcompeting the other candidates including AT3 (Pun1) from Capsicum spp. The CoA-ligase partner with highest activity from the ones evaluated here were from Petunia hybrida (PhCL) and Spingomonas sp. Ibu-2 (IpfF). A yeast strain expressing CaAT and IpfF produced 10.6 mg L−1 nonivamide in a controlled bioreactor setup, demonstrating nonivamide biosynthesis by S. cerevisiae for the first time.Baker’s yeast was engineered for production of nonivamide as a model capsaicinoid, by expressing N-acyltransferases
(Less)
and CoA-ligases of plant and bacterial origin. The constructed yeast
platform holds potential for in vivo biocatalytic formation of
capsaicinoids and could be a useful tool for the discovery of novel
drugs.
- author
- Muratovska, Nina LU ; Grey, Carl LU and Carlquist, Magnus LU
- organization
- publishing date
- 2022
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Capsaicinoids, Capsaicin, Chilli pepper, Capsicum, Fatty acids, Nonanoic acid, TRPV1 agonist, Yeast, Vanillylamine, N-Acyltransferase, CoA-ligase, Whole-cell bioconversion
- in
- Microbial Cell Factories
- volume
- 21
- article number
- 106
- pages
- 15 pages
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85130844411
- pmid:35643562
- ISSN
- 1475-2859
- DOI
- 10.1186/s12934-022-01831-3
- language
- English
- LU publication?
- yes
- id
- b408f2f6-c618-49db-9674-18caedc50766
- date added to LUP
- 2022-06-12 18:38:25
- date last changed
- 2023-01-21 21:17:48
@article{b408f2f6-c618-49db-9674-18caedc50766,
abstract = {{Background<p>Capsaicinoids are produced by plants in the <i>Capsicum</i><br>
genus and are the main reason for the pungency of chili pepper fruits. <br>
They are strong agonists of TRPV1 (the transient receptor potential <br>
cation channel subfamily V member 1) and used as active ingredients in <br>
pharmaceuticals for the treatment of pain. The use of bioengineered <br>
microorganisms in a fermentation process may be an efficient route for <br>
their preparation, as well as for the discovery of (bio-)synthetic <br>
capsaicinoids with improved or novel bioactivities.</p>Results<p><br>
<i>Saccharomyces cerevisiae</i> was engineered to over-express a selection of amide-forming <i>N</i>-acyltransferase<br>
and CoA-ligase enzyme cascades using a combinatorial gene assembly <br>
method, and was screened for nonivamide production from supplemented <br>
vanillylamine and nonanoic acid. Data from this work demonstrate that <br>
Tyramine <i>N-</i>hydroxycinnamoyl transferase from <i>Capsicum annuum</i> (CaAT) was most efficient for nonivamide formation in yeast, outcompeting the other candidates including AT3 (Pun1) from <i>Capsicum</i> spp. The CoA-ligase partner with highest activity from the ones evaluated here were from <i>Petunia hybrida</i> (PhCL) and <i>Spingomonas</i> sp.<i> Ibu-2</i> (IpfF). A yeast strain expressing CaAT and IpfF produced 10.6 mg L<sup>−1</sup> nonivamide in a controlled bioreactor setup, demonstrating nonivamide biosynthesis by <i>S. cerevisiae</i> for the first time.</p>Conclusions<p>Baker’s yeast was engineered for production of nonivamide as a model capsaicinoid, by expressing <i>N</i>-acyltransferases<br>
and CoA-ligases of plant and bacterial origin. The constructed yeast <br>
platform holds potential for in vivo biocatalytic formation of <br>
capsaicinoids and could be a useful tool for the discovery of novel <br>
drugs.</p>}},
author = {{Muratovska, Nina and Grey, Carl and Carlquist, Magnus}},
issn = {{1475-2859}},
keywords = {{Capsaicinoids; Capsaicin; Chilli pepper; Capsicum; Fatty acids; Nonanoic acid; TRPV1 agonist; Yeast; Vanillylamine; N-Acyltransferase; CoA-ligase; Whole-cell bioconversion}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{Microbial Cell Factories}},
title = {{Engineering <i>Saccharomyces cerevisiae</i> for production of the capsaicinoid nonivamide}},
url = {{http://dx.doi.org/10.1186/s12934-022-01831-3}},
doi = {{10.1186/s12934-022-01831-3}},
volume = {{21}},
year = {{2022}},
}