Sheridan, Kevin J. and Dolan, Stephen K. and Doyle, Sean (2015) Endogenous cross-talk of fungal metabolites. Frontiers in Microbiololgy, 5 (732). pp. 1-11. ISSN 1664-302X

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Abstract

Non-ribosomal peptide (NRP) synthesis in fungi requires a ready supply of proteogenic and non-proteogenic amino acids which are subsequently incorporated into the nascent NRP via a thiotemplate mechanism catalyzed by NRP synthetases. Substrate amino acids can be modified prior to or during incorporation into the NRP, or following incorporation into an early stage amino acid-containing biosynthetic intermediate. These post-incorporation modifications involve a range of additional enzymatic activities including but not exclusively, monooxygenases, methyltransferases, epimerases, oxidoreductases, and glutathione S-transferases which are essential to effect biosynthesis of the final NRP. Likewise, polyketide biosynthesis is directly by polyketide synthase megaenzymes and cluster-encoded ancillary decorating enzymes. Additionally, a suite of additional primary metabolites, for example: coenzyme A (CoA), acetyl CoA, S-adenosylmethionine, glutathione (GSH), NADPH, malonyl CoA, and molecular oxygen, amongst others are required for NRP and polyketide synthesis (PKS). Clearly these processes must involve exquisite orchestration to facilitate the simultaneous biosynthesis of different types of NRPs, polyketides, and related metabolites requiring identical or similar biosynthetic precursors or co-factors. Moreover, the near identical structures of many natural products within a given family (e.g., ergot alkaloids), along with localization to similar regions within fungi (e.g., conidia) suggests that cross-talk may exist, in terms of biosynthesis and functionality. Finally, we speculate if certain biosynthetic steps involved in NRP and PKS play a role in cellular protection or environmental adaptation, and wonder if these enzymatic reactions are of equivalent importance to the actual biosynthesis of the final metabolite.

Item Type:	Article
Additional Information:	Copyright © 2015 Sheridan, Dolan and Doyle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Citation: Sheridan KJ, Dolan SK and Doyle S (2015) Endogenous cross-talk of fungal metabolites. Front. Microbiol. 5:732. doi: 10.3389/fmicb.2014.00732
Keywords:	NRPS; gliotoxin; natural products; secondary metabolites; redox homeostasis; siderophores; systems biology; PKS;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	5729
Identification Number:	https://doi.org/10.3389/fmicb.2014.00732
Depositing User:	Dr. Sean Doyle
Date Deposited:	23 Jan 2015 17:20
Journal or Publication Title:	Frontiers in Microbiololgy
Publisher:	Frontiers
Refereed:	Yes
URI:
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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