Pentaketide Ansamycin Microansamycins A–I from Micromonospora sp. Reveal Diverse Post-PKS Modifications

Overexpression of the pathway-specific positive regulator gene <i>mas13</i> activated the cryptic gene cluster <i>mas</i>, resulting in the isolation of nine novel pentaketide ansamycins, namely, microansamycins A–I (<b>1</b>–<b>9</b>). These results not only revealed a biosynthetic gene cluster of pentaketide ansamycins for the first time but also presented an unprecedented scenario of diverse post-PKS modifications in ansamycin biosynthesis

Enhancing the Performance of Perovskite Solar Cells via the Functional Group Synergistic Effect in Interfacial Passivation Materials

Interfacial defects are considered to be a stumbling block in producing highly efficient perovskite solar cells (PSCs), so a more reasonable design is required for interfacial passivation materials (IPMs) to achieve further improvements in PSC performance. Here, we use fluorine atom (−F) and methoxy (−OCH3) functional groups to modify the same molecular fragment, obtaining three kinds of IPMs named YZ-301, YZ-302, and YZ-303, respectively. Through the subtle combination of −F and −OCH3, the fragment in YZ-302 exhibits an enhanced electronegativity, rendering the correlative IPM with a stronger interaction with the perovskite layer. As a result, YZ-302 shows the best defect passivation and hole transport effect at the interface, and the PSC based on YZ-302 treatment achieves the best efficiency approaching 24%, which is better than the reference and devices with other IPMs, and it also has excellent device stability

Identification and Characterization of the 28‑<i>N</i>‑Methyltransferase Involved in HSAF Analogue Biosynthesis

Polycyclic tetramate macrolactams (PoTeMs) are a family of structurally intriguing bioactive natural products. Although the presence of the N-28 methyl group is known to affect bioactivities of some PoTeMs, the mechanism for this methylation remains unclear. We report here the identification and characterization of the 28-N-methyltransferase for HSAF analogues, which is encoded by a gene located outside the HSAF (heat-stable antifungal factor) cluster in Lysobacter enzymogenes C3. Our data suggested that 28-N-methyltransferase utilizes S-adenosylmethionine (SAM) to methylate HSAF analogues, and acts after the dicyclic and tricyclic ring formation and prior to C-3 hydroxylation. Kinetic analysis showed that the optimal substrate for the enzyme is 3-dehydroxy HSAF (3-deOH HSAF). Moreover, it could also accept PoTeMs bearing a 5–6 or 5–6–5 polycyclic system as substrates. This is the first N-methyltransferase identified in the family of PoTeMs, and the identification of this enzyme provides a new tool to generate new PoTeMs as antibiotic lead compounds

Structure Engineering of Hole–Conductor Free Perovskite-Based Solar Cells with Low-Temperature-Processed Commercial Carbon Paste As Cathode

Low-temperature-processed (100 °C) carbon paste was developed as counter electrode material in hole–conductor free perovskite/TiO₂ heterojunction solar cells to substitute noble metallic materials. Under optimized conditions, an impressive PCE value of 8.31% has been achieved with this carbon counter electrode fabricated by doctor-blading technique. Electrochemical impedance spectroscopy demonstrates good charge transport characteristics of low-temperature-processed carbon counter electrode. Moreover, this carbon counter electrode-based perovskite solar cell exhibits good stability over 800 h

Activating a Cryptic Ansamycin Biosynthetic Gene Cluster To Produce Three New Naphthalenic Octaketide Ansamycins with <i>n</i>‑Pentyl and <i>n</i>‑Butyl Side Chains

Genome mining is a rational approach to discovering new natural products. The genome sequence analysis of <i>Streptomyces</i> sp. LZ35 revealed the presence of a putative ansamycin gene cluster (<i>nam</i>). Constitutive overexpression of the pathway-specific transcriptional regulatory gene <i>nam1</i> successfully activated the <i>nam</i> gene cluster, and three novel naphthalenic octaketide ansamycins were discovered with unprecedented <i>n</i>-pentylmalonyl-CoA or <i>n</i>-butylmalonyl-CoA extender units. This study represents the first example of discovering novel ansamycin scaffolds via activation of a cryptic gene cluster

Hygrocins C–G, Cytotoxic Naphthoquinone Ansamycins from <i>gdmAI</i>-Disrupted <i>Streptomyces</i> sp. LZ35

Six hygrocins, polyketides of ansamycin class, were isolated from the <i>gdmAI</i>-disrupted Streptomyces sp. LZ35. The planar structure of hygrocins C–E (<b>1</b>–<b>3</b>) was determined by one-dimensional and two-dimensional NMR spectroscopy and high-resolution mass spectrometry. They are derivatives of hygrocin A but differ in the configuration at C-2 and the orientation of the C-3,4 double bond. Hygrocin F­(<b>4</b>) and G­(<b>5</b>) were shown to be isomers of hygrocin C (<b>1</b>) and B (<b>6</b>), respectively, due to the different alkyl oxygen participating in the macrolide ester linkage. Hygrocins C, D, and F were found to be toxic to human breast cancer MDA-MB-431 cells (IC₅₀ = 0.5, 3.0, and 3.3 μM, respectively) and prostate cancer PC3 cells (IC₅₀ = 1.9, 5.0, and 4.5 μM, respectively), while hygrocins B, E, and G were inactive

d‑Alanylation in the Assembly of Ansatrienin Side Chain Is Catalyzed by a Modular NRPS

Ansatrienins are a group of ansamycins with an <i>N</i>-cyclohexanoyl d-alanyl side chain. Though ansatrienins have been identified for decades, the mechanism for the addition of this unique side chain was not established. Here, we report the biochemical characterization of a tridomain nonribosomal peptide synthetase (NRPS), AstC, and an <i>N</i>-acyltransferase, AstF1, encoded in the biosynthetic pathway of ansatrienins. We demonstrate that AstC can efficiently catalyze the transfer of d-alanine to the C-11 hydroxyl group of ansatrienins, and AstF1 is able to attach the cyclohexanoyl group to the amino group of d-alanine. Remarkably, AstC presents the first example that a modular NRPS can catalyze intermolecular d-alanylation of the hydroxyl group to form an ester bond, though alanyl natural products have been known for decades. In addition, both AstC and AstF1 have broad substrate specificity toward acyl donors, which can be utilized to create novel ansatrienins

Targeted Discovery and Combinatorial Biosynthesis of Polycyclic Tetramate Macrolactam Combamides A–E

Polycyclic tetramate macrolactams (PoTeMs) are a growing class of natural products with distinct structure and diverse biological activities. By promoter engineering and heterologous expression of the cryptic <i>cbm</i> gene cluster, four new PoTeMs, combamides A–E (<b>1</b>–<b>4</b>), were identified. Additionally, two new derivatives, combamides E (<b>5</b>) and F (<b>6</b>), were generated via combinatorial biosynthesis. Together, our findings provide a sound base for expanding the structure diversities of PoTeMs through genome mining and combinatorial biosynthesis