Synlett
DOI: 10.1055/s-0036-1588526
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© Georg Thieme Verlag Stuttgart · New York

Fungal Dihydroxynaphthalene-Melanin: Diversity-Oriented Biosynthesis through Enzymatic and Non-enzymatic Transformations

Syed Masood Husaina, Michael Müller*b
  • aMolecular Synthesis & Drug Discovery Unit, Centre of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus, Raebareli Road, Lucknow 226014, India
  • bInstitut für Pharmazeutische Wissenschaften, Albert-Ludwigs-Universität Freiburg, Albertstr. 25, D-79104 Freiburg, Germany   Email: michael.mueller@pharmazie.uni-freiburg.de
S.M.H. is grateful to the Council of Scientific and Industrial Research, New Delhi [Project No. 02(0258)/16/EMR-II] and SERB-DST (YSS/2014/000792) for funding
Further Information

Publication History

Received: 20 May 2017

Accepted after revision: 03 July 2017

Publication Date:
31 August 2017 (eFirst)

Abstract

Tetrahydroxynaphthalene reductase (T4HNR) from Magnaporthe grisea catalyzes the reduction of polyhydroxynaphthalenes, hydroxynaphthoquinones, and 1,4-diketones, with extensive ramifications for the biosynthesis of (shunt) metabolites related to 1,8-dihydroxynaphthalene (DHN)-melanin biosynthesis. Hence, an extended model for DHN-melanin biosynthesis has been developed which is based on a screening hypothesis involving non-enzymatic transformations such as oxidations and tautomerism. This has led to the broadening of the functions of several short-chain dehydrogenases/reductases (SDRs) capable of reducing polyhydroxyanthracenes, polyhydroxynaphthalenes, and polyhydroxybenzenes. Our work, broadening the scope of enzymatic dearomatization reactions, provides access to the biocatalytic synthesis of a variety of natural and natural-like products. Furthermore, the results described in this account provide the basis for the identification of other SDRs amenable to reducing aromatic compounds, and thus enable the identification of biosynthetic gene clusters most likely involved in the biosynthesis of aromatic polyketides.

1 Introduction

2 Biosynthesis of 1,8-Dihydroxynaphthalene (DHN)

3 Biosynthesis of Shunt Metabolites and the Origin of Molecular Diversity

3.1 Role of Spontaneous Non-enzymatic Oxidations

3.2 Role of T4HNR and T3HNR

3.3 Role of Tautomerism in the Biosynthesis of (Shunt) Metabolites

4 Extended Melanin Biosynthesis: A Screening Hypothesis

5 Useful Outcomes of the Newly Identified Melanin Biosynthetic Pathway

5.1 NADP+ Regeneration Using Lawsone as Mediator

5.2 Anthrahydroquinone as an Intermediate in the Biosynthesis of Chrysophanol and Other Anthraquinone-Derived Products

5.3 Combination of T3HNR and GDH To Access trans-Ketodiols

5.4 Phloroglucinol Reductases (PGRs) To Dearomatize Monomeric Phenols

6 Conclusion