Details:

Alternative Title:
J Am Chem Soc
Publisher's site:
http://dx.doi.org/10.1021/jacs.5b06108
Personal Author:
Tang, Mancheng ; Lin, Hsiao-Ching ; Li, Dehai ; Zou, Yi ; Li, Jian ; ... More +
Tang, Mancheng ; Lin, Hsiao-Ching ; Li, Dehai ; Zou, Yi ; Li, Jian ; Xu, Wei ; Cacho, Ralph A. ; Hillenmeyer, Maureen E. ; Garg, Neil K. ; Tang, Yi Less -
Description:
The structural diversity and biological activities of fungal indole diterpenes (IDTs) are generated in large part by the IDT cyclases (IDTCs). Identifying different IDTCs from IDT biosynthetic pathways is therefore important toward understanding how these enzymes introduce chemical diversity from a common linear precursor. However, IDTCs involved in the cyclization of the well-known aflavinine subgroup of IDTs have not been discovered. Here, using Saccharomyces cerevisiae as a heterologous host and a phylogenetically guided enzyme mining approach, we combinatorially assembled IDT biosynthetic pathways using IDTCs homologues identified from different fungal hosts. We identified the genetically standalone IDTCs involved in the cyclization of aflavinine and anominine and produced new IDTs not previously isolated. The cyclization mechanisms of the new IDTCs were proposed based on the yeast reconstitution results. Our studies demonstrate heterologous pathway assembly is a useful tool in the reconstitution of unclustered biosynthetic pathways.
Subject:
[+]
Article
Biosynthetic Pathways
Cyclization
Diterpenes
Genetic Engineering
Indoles
Molecular Conformation
Phosphorus-Oxygen Lyases
Saccharomyces Cerevisiae

Source:
J Am Chem Soc. 137(43):13724-13727.
Pubmed ID:
26469304
Pubmed Central ID:
PMC4732561
Document Type:
Journal Article
Funding:
DP1 GM106413/GM/NIGMS NIH HHS/United States ; P01 HG000205/HG/NHGRI NIH HHS/United States ; U01 GM110706/GM/NIGMS NIH HHS/United States ; 1DP1GM106413/DP/NCCDPHP CDC HHS/United States ; 1U01GM110706-01/GM/NIGMS NIH HHS/United States
DP1 GM106413/GM/NIGMS NIH HHS/United States ; P01 HG000205/HG/NHGRI NIH HHS/United States ; U01 GM110706/GM/NIGMS NIH HHS/United States ; 1DP1GM106413/DP/NCCDPHP CDC HHS/United States ; 1U01GM110706-01/GM/NIGMS NIH HHS/United States Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:0829777a2d6758b952661c5c47cecac15713457228e416e671f216630f4dc562
File Type:

Supporting Files

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