Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite

Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para-cyclophane ether. Herein, we identified new xenoacremones A, B, and C (1−3) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in...

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Autores principales:	Zhiguo Liu, Wei Li, Peng Zhang, Jie Fan, Fangbo Zhang, Caixia Wang, Shuming Li, Yi Sun, Shilin Chen, Wenbing Yin
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Tyrosine-decahydrofluorene Biosynthesis PKS−NRPS Xenoacremone Heterologous expression Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/caf180bc9d3845dcaaa78713066b742e
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spelling	oai:doaj.org-article:caf180bc9d3845dcaaa78713066b742e2021-12-02T05:01:22ZTricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite2211-383510.1016/j.apsb.2021.03.034https://doaj.org/article/caf180bc9d3845dcaaa78713066b742e2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211383521001064https://doaj.org/toc/2211-3835Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para-cyclophane ether. Herein, we identified new xenoacremones A, B, and C (1−3) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans. The hybrid polyketide synthase–nonribosomal peptide synthetase (PKS−NRPS) XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton. This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety. XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system. Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether, which underwent subsequent spontaneous Diels−Alder reaction to give the end products. Thus, the results indicated that three novel enzymes XenF, XenD, and XenC coordinate to assemble the [6.5.6] tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.Zhiguo LiuWei LiPeng ZhangJie FanFangbo ZhangCaixia WangShuming LiYi SunShilin ChenWenbing YinElsevierarticleTyrosine-decahydrofluoreneBiosynthesisPKS−NRPSXenoacremoneHeterologous expressionTherapeutics. PharmacologyRM1-950ENActa Pharmaceutica Sinica B, Vol 11, Iss 11, Pp 3655-3664 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tyrosine-decahydrofluorene Biosynthesis PKS−NRPS Xenoacremone Heterologous expression Therapeutics. Pharmacology RM1-950
spellingShingle	Tyrosine-decahydrofluorene Biosynthesis PKS−NRPS Xenoacremone Heterologous expression Therapeutics. Pharmacology RM1-950 Zhiguo Liu Wei Li Peng Zhang Jie Fan Fangbo Zhang Caixia Wang Shuming Li Yi Sun Shilin Chen Wenbing Yin Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
description	Tyrosine-decahydrofluorene derivatives feature a fused [6.5.6] tricarbocyclic core and a 13-membered para-cyclophane ether. Herein, we identified new xenoacremones A, B, and C (1−3) from the fungal strain Xenoacremonium sinensis ML-31 and elucidated their biosynthetic pathway using gene deletion in the native strain and heterologous expression in Aspergillus nidulans. The hybrid polyketide synthase–nonribosomal peptide synthetase (PKS−NRPS) XenE together with enoyl reductase XenG were confirmed to be responsible for the formation of the tyrosine-nonaketide skeleton. This skeleton was subsequently dehydrated by XenA to afford a pyrrolidinone moiety. XenF catalyzed a novel sigmatropic rearrangement to yield a key cyclohexane intermediate as a prerequisite for the formation of the multi-ring system. Subsequent oxidation catalyzed by XenD supplied the substrate for XenC to link the para-cyclophane ether, which underwent subsequent spontaneous Diels−Alder reaction to give the end products. Thus, the results indicated that three novel enzymes XenF, XenD, and XenC coordinate to assemble the [6.5.6] tricarbocyclic ring and para-cyclophane ether during biosynthesis of complex tyrosine-decahydrofluorene derivatives.
format	article
author	Zhiguo Liu Wei Li Peng Zhang Jie Fan Fangbo Zhang Caixia Wang Shuming Li Yi Sun Shilin Chen Wenbing Yin
author_facet	Zhiguo Liu Wei Li Peng Zhang Jie Fan Fangbo Zhang Caixia Wang Shuming Li Yi Sun Shilin Chen Wenbing Yin
author_sort	Zhiguo Liu
title	Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
title_short	Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
title_full	Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
title_fullStr	Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
title_full_unstemmed	Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite
title_sort	tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with xenf-mediated sigmatropic rearrangement as a prerequisite
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/caf180bc9d3845dcaaa78713066b742e
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Tricarbocyclic core formation of tyrosine-decahydrofluorenes implies a three-enzyme cascade with XenF-mediated sigmatropic rearrangement as a prerequisite

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