Biosynthesis of Phomactin Platelet Activating Factor Antagonist Requires a Two-Enzyme Cascade.

Phomactin diterpenoids possess a unique bicyclo[9.3.1]pentadecane skeleton with multiple oxidative modifications, and are good platelet-activating factor (PAF) antagonists that can inhibit PAF-induced platelet aggregation.

Building as a chassis for synthesis of bacterial terpenoids.

Terpenoids comprise the most chemically and structurally diverse family of natural products. In contrast to the huge numbers of terpenoids discovered from plants and fungi, only a relatively small number of terpenoids were reported from bacteria. Recent genomic data in bacteria suggest that a large number of biosynthetic gene clusters encoding terpenoids remain uncharacterized.

Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments.

AvmM catalyses macrocyclization through dehydration/Michael-type addition in alchivemycin A biosynthesis.

Macrocyclization is an important process that affords morphed scaffold in biosynthesis of bioactive natural products. Nature has adapted diverse biosynthetic strategies to form macrocycles. In this work, we report the identification and characterization of a small enzyme AvmM that can catalyze the construction of a 16-membered macrocyclic ring in the biosynthesis of alchivemycin A (1).

A BBE-like Oxidase, AsmF, Dictates the Formation of Naphthalenic Hydroxyl Groups in Ansaseomycin Biosynthesis.

Ansaseomycins are ansamycin-type natural products produced through expression of the gene cluster in a heterologous host. A rare berberine bridge enzyme (BBE) like oxidase, AsmF, is encoded in the gene cluster. Deletion of led to the accumulation of a series of structurally diverse compounds, all of which lacked the 23-hydroxyl group in naphthalenic motif.

Redox Modifications in the Biosynthesis of Alchivemycin A Enable the Formation of Its Key Pharmacophore.

Redox enzymes play a critical role in transforming nascent scaffolds into structurally complex and biologically active natural products. Alchivemycin A (AVM, ) is a highly oxidized polycyclic compound with potent antimicrobial activity and features a rare 2-tetrahydro-4,6-dioxo-1,2-oxazine (TDO) ring system. The scaffold of AVM has previously been shown to be biosynthesized by a hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) pathway.

Heterologous Expression of a Cryptic Giant Type I PKS Gene Cluster Leads to the Production of Ansaseomycin.

Genome mining of the marine Streptomyces seoulensis A01 enabled the identification of a giant type I polyketide synthase gene cluster ( asm). Heterologous expression of the cryptic asm cluster using a bacterial artificial chromosome vector in heterologous host led to the production of ansaseomycins A (1) and B (2). A plausible biosynthetic pathway was also proposed.

A new spectinabilin derivative with cytotoxic activity from ant-derived Streptomyces sp. 1H-GS5.

A new spectinabilin derivative (1) was isolated from the fermentation broth of the ant-derived Streptomyces sp. 1H-GS5, and the structure was elucidated by extensive spectroscopic analysis. Compound 1 showed cytotoxicity against human tumor cell lines A549, HCT-116, and HepG2 with IC values of 9.