Reconstitution of Polyketide-Derived Meroterpenoid Biosynthetic Pathway in Aspergillus oryzae

The heterologous gene expression system with Aspergillus oryzae as the host is an effective method to investigate fungal secondary metabolite biosynthetic pathways for reconstruction to produce un-natural molecules due to its high productivity and genetic tractability. In this review, we focus on biosynthetic studies of fungal polyketide-derived meroterpenoids, a group of bioactive natural products, by means of the A. oryzae heterologous expression system. The heterologous expression methods and the biosynthetic reactions are described in detail for future prospects to create un-natural molecules via biosynthetic re-design.

Biosynthesis of the Tricyclic Aromatic Type II Polyketide Rishirilide: New Potential Third Ring Oxygenation after Three Cyclization Steps

Rishirilides are a group of PKS II secondary metabolites produced by Streptomyces bottropensis Gö C4/4. Biosynthetic studies in the past have elucidated early and late steps of rishirilide biosynthesis. This work is aiming to solve the remaining steps in the rishirilide biosynthesis. Inactivation of the cyclase gene rslC3 in Streptomyces bottropensis resulted in an interruption of rishirilide production. Instead, accumulation of the tricyclic aromatic galvaquinones was observed. Similar results were observed after deletion of rslO4. Closer inspection into RslO4 crystal structure in addition to site-directed mutagenesis and molecular dynamic simulations revealed that RslO4 might be responsible for quinone formation on the third ring. The RslO1 three-dimensional structure shows a high similarity to FMN-dependent luciferase-like monooxygenases such as the epoxy-forming MsnO8 which acts with the flavin reductase MsnO3 in mensacarcin biosynthesis in the same strain. The high sequence similarity between RslO2 and MsnO3 suggests that RslO2 provides RslO1 with reduced FMN to form an epoxide that serves as substrate for RslO5.

Recent highlights of biosynthetic studies on marine natural products

Marine bacteria are excellent yet often underexplored sources of structurally unique bioactive natural products.

SOME MOLECULAR ASPECTS OF PLANT PEROXIDASE BIOSYNTHETIC STUDIES

The early history of research on peroxidase is most capably reviewed bySaunders et al (67). The first color reaction of biological material withguaiacum as substrate was noted in 1809, but the term peroxidase was usedfor the first time nearly a century later for an enzyme isolated from horseradish.In fact, peroxidase is widely distributed in the plant kingdom and also occurs in the animal kingdom. Many of the spectral aspects of this hemoproteinand its reaction products have been described in the above-mentioned textand elsewhere (e.g. 23). Different types of peroxidases were recognized, andan ever-increasing number of functions were ascribed to them, particularly inplant physiology (31). Therefore, while the basic chemical reactions ofperoxidase (E. C . 1.1 1.1. 7) are well established, namely that of the peroxidaticcycle involving H202 and a large array of hydrogen donors (23), the questionsof how its many isozymes function (31) and how its action in differentiation iscontrolled (68) remain largely unanswered. I do not review all publications onthese topics here. A comprehensive tabulation has appeared recently (31).Instead, I offer a critical review of certain aspects of peroxidase in terms ofstructure and biosynthesis.

Marine Natural Products with High Anticancer Activities

This review covers recent literature from 2012-2019 concerning 170 marine natural products and their semisynthetic analogues with strong anticancer biological activities. Reports that shed light on cellular and molecular mechanisms and biological functions of these compounds, thus advancing the understanding in cancer biology are also included. Biosynthetic studies and total syntheses, which have provided access to derivatives and have contributed to the proper structure or stereochemistry elucidation or revision are mentioned. The natural compounds isolated from marine organisms are divided into nine groups, namely: alkaloids, sterols and steroids, glycosides, terpenes and terpenoids, macrolides, polypeptides, quinones, phenols and polyphenols, and miscellaneous products. An emphasis is placed on several drugs originating from marine natural products that have already been marketed or are currently in clinical trials.

Biosynthetic studies of novel polyketides from the marine sponge-derived fungusStachylidiumsp. 293K04

A methylation of the acetate starter unit is part of the polyketide biosynthesis of phthalides and phthalimidines from the marine-derived fungusStachylidiumsp. 293K04.

Anthracimycin B, a Potent Antibiotic against Gram-Positive Bacteria Isolated from Cultures of the Deep-Sea Actinomycete Streptomyces cyaneofuscatus M-169

The potent antimicrobial extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-169 was fractionated by reversed phase flash chromatography and preparative HPLC to yield the new Gram-positive antibiotic, anthracimycin B (1), together with its congener, anthracimycin (2). The structure of the new compound was established by analysis of its ESI-TOF MS and 1D and 2D NMR spectra, and comparison with data published for anthracimycin and anthracimycin BII-2619 (3). Notably, anthracimycin seemed to be the major and almost unique component of the extract detected by HPLC-UV-MS, making our S. cyanofuscatus strain an excellent candidate for further biosynthetic studies of this potent antibiotic.