TL;DR
It is indicated that combining A-domain substrate prediction with genome mining is an effective strategy for discovering NRPs in Aspergillus, expanding the understanding of their biosynthetic potential.
PA1216, a putative methyltransferase embedded within an NRPS BGC in Pseudomonas aeruginosa strain PAO1 is characterized and a platform for characterizing cryptic gene clusters within secondary metabolic pathways is established for characterizing cryptic gene clusters within secondary metabolic pathways.
An alkaliphilic strain of Streptomyces S9 was isolated and taxonomically characterised through multilocus sequence analysis (MLSA) using Streptomyces-specific primers, indicating its genetic potential to biosynthesise aromatic polyketides.
Genome mining of the marine-derived Streptomyces sp. S42 uncovered a type II polyketide synthetase (T2 PKS) biosynthetic gene cluster (BGC) harboring a gene for 3-ketoacyl-ACP synthase III (KAS III), a hallmark of non-acetate starter unit incorporation, suggesting that the BGC may produce previously unidentified aromatic polyketides. Heterologous expression and promoter engineering of this prioritized BGC in host Streptomyces albus J1074 activated the biosynthetic pathway, leading to the isolation of eight new polycyclic aromatic derivatives, verrucones A–H (1–8). Comprehensive structural elucidation via NMR and HRESIMS revealed that these compounds feature either a 2-methylbutyryl or an isobutyryl starter unit and can be classified into three distinct skeletal types. Based on these findings and bioinformatic analysis, a plausible biosynthetic pathway for 1–8 involving divergent spontaneous cyclization from a common nascent polyketide intermediate was proposed. Among the isolated compounds, 1–5 exhibited inhibitory activity against several protein tyrosine phosphatases (PTPs) with IC50 values ranging from 1.84 μM to 24.82 μM. This study presents a successful case study demonstrating that combining KAS III-targeted genome mining with heterologous expression is a viable approach for discovering non-acetate-primed aromatic polyketides.
Findings indicate that Pseudoduganella sp.
Elucidating natural products encoded by cryptic biosynthetic gene clusters (BGCs) in agriculturally important biocontrol fungi such as Trichoderma afroharzianum T22 (ThT22) could lead to the discovery of new compounds that may be explored as potential agrochemicals. Herein, we discovered new lipopeptide natural products, trichopeptide A-D, via genome mining and heterologous reconstitution of the tep BGC from ThT22. Comprehensive NMR, high-resolution mass spectrometry (HRMS), tandem mass spectrometry (MS/MS), Marfey's analysis, and chemical synthesis experiments established the structures of trichopeptides as linear pentapeptides acylated with a conjugated triene acid at the N-terminus. A notable structural feature of trichopeptides is the presence of a nonproteinogenic amino acid residue, (Z)-dehydrobutyrine, in the linear peptide. The residue is proposed to be derived from threonine by the action of a noncanonical dehydrating condensation domain (DhC) in the nonribosomal peptide synthetase (NRPS) TepB. This represents only the second example in which a fungal NRPS is responsible for the biosynthesis of dehydroamino acids in a peptide product. Our results expand the chemical inventory of an agriculturally important fungus and pave the way for the future investigation of possible plant-ThT22 interactions mediated by lipopeptides.
Findings suggest that strain D18 possesses adaptive strategies for survival in deep-sea environments and highlight its potential as a source of novel secondary metabolites.
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