Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast

Abstract Tsetse flies are the transmitting vector of trypanosomes causing human sleeping sickness and animal trypanosomiasis in sub-saharan Africa. 3-alkylphenols are used as attractants in tsetse fly traps to reduce the spread of the disease. Here we present an inexpensive production method for 3-e...

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Autores principales:	Julia Hitschler, Martin Grininger, Eckhard Boles
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/baea499fd6f146c7874810cf2983284d
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spelling	oai:doaj.org-article:baea499fd6f146c7874810cf2983284d2021-12-02T17:40:46ZSubstrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast10.1038/s41598-020-66997-52045-2322https://doaj.org/article/baea499fd6f146c7874810cf2983284d2020-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-66997-5https://doaj.org/toc/2045-2322Abstract Tsetse flies are the transmitting vector of trypanosomes causing human sleeping sickness and animal trypanosomiasis in sub-saharan Africa. 3-alkylphenols are used as attractants in tsetse fly traps to reduce the spread of the disease. Here we present an inexpensive production method for 3-ethylphenol (3-EP) and 3-propylphenol (3-PP) by microbial fermentation of sugars. Heterologous expression in the yeast Saccharomyces cerevisiae of phosphopantetheinyltransferase-activated 6-methylsalicylic acid (6-MSA) synthase (MSAS) and 6-MSA decarboxylase converted acetyl-CoA as a priming unit via 6-MSA into 3-methylphenol (3-MP). We exploited the substrate promiscuity of MSAS to utilize propionyl-CoA and butyryl-CoA as alternative priming units and the substrate promiscuity of 6-MSA decarboxylase to produce 3-EP and 3-PP in yeast fermentations. Increasing the formation of propionyl-CoA by expression of a bacterial propionyl-CoA synthetase, feeding of propionate and blocking propionyl-CoA degradation led to the production of up to 12.5 mg/L 3-EP. Introduction of a heterologous ‘reverse ß-oxidation’ pathway provided enough butyryl-CoA for the production of 3-PP, reaching titers of up to 2.6 mg/L. As the concentrations of 3-alkylphenols are close to the range of the concentrations deployed in tsetse fly traps, the yeast broths might become promising and inexpensive sources for attractants, producible on site by rural communities in Africa.Julia HitschlerMartin GriningerEckhard BolesNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-11 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julia Hitschler Martin Grininger Eckhard Boles Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
description	Abstract Tsetse flies are the transmitting vector of trypanosomes causing human sleeping sickness and animal trypanosomiasis in sub-saharan Africa. 3-alkylphenols are used as attractants in tsetse fly traps to reduce the spread of the disease. Here we present an inexpensive production method for 3-ethylphenol (3-EP) and 3-propylphenol (3-PP) by microbial fermentation of sugars. Heterologous expression in the yeast Saccharomyces cerevisiae of phosphopantetheinyltransferase-activated 6-methylsalicylic acid (6-MSA) synthase (MSAS) and 6-MSA decarboxylase converted acetyl-CoA as a priming unit via 6-MSA into 3-methylphenol (3-MP). We exploited the substrate promiscuity of MSAS to utilize propionyl-CoA and butyryl-CoA as alternative priming units and the substrate promiscuity of 6-MSA decarboxylase to produce 3-EP and 3-PP in yeast fermentations. Increasing the formation of propionyl-CoA by expression of a bacterial propionyl-CoA synthetase, feeding of propionate and blocking propionyl-CoA degradation led to the production of up to 12.5 mg/L 3-EP. Introduction of a heterologous ‘reverse ß-oxidation’ pathway provided enough butyryl-CoA for the production of 3-PP, reaching titers of up to 2.6 mg/L. As the concentrations of 3-alkylphenols are close to the range of the concentrations deployed in tsetse fly traps, the yeast broths might become promising and inexpensive sources for attractants, producible on site by rural communities in Africa.
format	article
author	Julia Hitschler Martin Grininger Eckhard Boles
author_facet	Julia Hitschler Martin Grininger Eckhard Boles
author_sort	Julia Hitschler
title	Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
title_short	Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
title_full	Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
title_fullStr	Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
title_full_unstemmed	Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
title_sort	substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/baea499fd6f146c7874810cf2983284d
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Substrate promiscuity of polyketide synthase enables production of tsetse fly attractants 3-ethylphenol and 3-propylphenol by engineering precursor supply in yeast

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