Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis

Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9‐membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruptio...

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Autores principales: Williams, Katherine, Szwalbe, Agnieszka J., Mulholland, Nicholas P., Vincent, Jason L., Bailey, Andrew M., Willis, Christine L., Simpson, Thomas J., Cox, Russell J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982102/
https://www.ncbi.nlm.nih.gov/pubmed/27099957
http://dx.doi.org/10.1002/anie.201511882
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author Williams, Katherine
Szwalbe, Agnieszka J.
Mulholland, Nicholas P.
Vincent, Jason L.
Bailey, Andrew M.
Willis, Christine L.
Simpson, Thomas J.
Cox, Russell J.
author_facet Williams, Katherine
Szwalbe, Agnieszka J.
Mulholland, Nicholas P.
Vincent, Jason L.
Bailey, Andrew M.
Willis, Christine L.
Simpson, Thomas J.
Cox, Russell J.
author_sort Williams, Katherine
collection PubMed
description Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9‐membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate‐processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine‐binding proteins.
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spelling pubmed-49821022016-08-26 Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis Williams, Katherine Szwalbe, Agnieszka J. Mulholland, Nicholas P. Vincent, Jason L. Bailey, Andrew M. Willis, Christine L. Simpson, Thomas J. Cox, Russell J. Angew Chem Int Ed Engl Communications Fungal maleidrides are an important family of bioactive secondary metabolites that consist of 7, 8, or 9‐membered carbocycles with one or two fused maleic anhydride moieties. The biosynthesis of byssochlamic acid (a nonadride) and agnestadride A (a heptadride) was investigated through gene disruption and heterologous expression experiments. The results reveal that the precursors for cyclization are formed by an iterative highly reducing fungal polyketide synthase supported by a hydrolase, together with two citrate‐processing enzymes. The enigmatic ring formation is catalyzed by two proteins with homology to ketosteroid isomerases, and assisted by two proteins with homology to phosphatidylethanolamine‐binding proteins. John Wiley and Sons Inc. 2016-04-21 2016-06-01 /pmc/articles/PMC4982102/ /pubmed/27099957 http://dx.doi.org/10.1002/anie.201511882 Text en © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Williams, Katherine
Szwalbe, Agnieszka J.
Mulholland, Nicholas P.
Vincent, Jason L.
Bailey, Andrew M.
Willis, Christine L.
Simpson, Thomas J.
Cox, Russell J.
Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
title Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
title_full Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
title_fullStr Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
title_full_unstemmed Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
title_short Heterologous Production of Fungal Maleidrides Reveals the Cryptic Cyclization Involved in their Biosynthesis
title_sort heterologous production of fungal maleidrides reveals the cryptic cyclization involved in their biosynthesis
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982102/
https://www.ncbi.nlm.nih.gov/pubmed/27099957
http://dx.doi.org/10.1002/anie.201511882
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