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An improved synthesis for tryptophan-dehydrobutyrine diketopiperazine (TDD), a co-metabolite of the hybrid polyketide/non-ribosomal peptide hangtaimycin, starting from ʟ-tryptophan is presented. Comparison to TDD isolated from the hangtaimycin producer Streptomyces spectabilis confirmed its S configuration. The X-ray structure of the racemate shows an interesting dimerisation through hydrogen bridges. The results from bioactivity testings of hangtaimycin, TDD and the hangtaimycin degradation product HTM222 are given.

Anapole modes supported by the well-designed dielectric nanostructure have attracted extensive concerns in the field of nanophotonic applications owing to its unique strong near-field enhancement and nonradiative far-field scattering characteristics, yet it is still difficult to achieve high Q-factor resonance features with narrow linewidth. In this work, a periodic slotted silicon nanodisk array is theoretically proposed to realize narrow linewidth and high Q-factor resonance in the near-infrared wavelength range. Through introducing the coupling between the anapole modes in the single dielectric nanostructure and the diffractive wave mode arisen from the periodic array, the as-designed dielectric nanostructure synchronously manifests excellent spectral features with a bandwidth as narrow as about 2.0 nm, a large Q-factor of 599, perfect transmission amplitude attaining 96% and relatively high electric field intensity (> 2809 times) in the middle of the slotted silicon nanodisk. The as-designed nanostructure possessing these outstanding optical features can work as a high-efficiency refractive-index sensor, whose sensitivity can reach 161.5 nm/RIU with its figure of merit attaining 80.8 RIU−1, efficiently distinguishing an index change of less than 0.01. The proposed slotted silicon nanodisk array exhibits tremendous potential for expanding the application such as label-free biochemical sensing, plasmonic refractive index sensing and surface enhancement spectroscopy.

The emerging of superbugs has led to an urgent need for novel antibiotics. Antimicrobial peptides (AMPs) characterized with broad-spectrum antibacterial activity, reduced resistance, and immune stimulation, show application prospects in combating drug-resistant microorganisms. In this study, computational techniques were used to design BamA targeted AMPs. Designed AMPs were then synthesized and investigated for their antibacterial activities, mechanisms, and stability. Molecular docking and dynamics simulations revealed that both the designed AMPs of 11pep and D-11pep could polymerize the β1, β9, β15, and β16 chains of BamA, leading to faulty folding of outer membrane proteins and resulting in antibacterial effects. Further antibacterial studies showed that 11pep and D-11pep have broad-spectrum activity, and D-11pep exhibiting more potent antibacterial action against resistant Gram-negative bacteria with MICs of 16 μg/mL, 8 μg/mL and 32 μg/mL against carbapenem-resistant Escherichia coli, carbapenem-resistant Pseudomonas aeruginosa, and multi-drug resistant Acinetobacter baumannii, respectively, and lower resistance induction. Mechanism investigation of 11pep and D-11pep showed that, both peptides could disrupt the bacterial outer membrane, which was consistent with the molecular dynamics simulations, and D-11pep is more stable and less toxic than 11pep. Results in this study indicate that rational design of AMPs targeted BamA, and the D-amino acid replacement strategy are useful tactics to develop drug-resistant bacteria AMPs.

By manipulating the Zn2+ coordination environment, electrolytes with diverse Zn2+–En configurations effectively inhibit zinc dendrite growth and side reactions.

By using ethylenediamine (En) as a complexing agent, the impact of various Zn

Streptovaricin C is a naphthalenic ansamycin antibiotic structurally similar to rifamycins with potential anti-MRSA bioactivities. However, the formation mechanism of the most fascinating and bioactivity-related methylenedioxy bridge (MDB) moiety in streptovaricins is unclear. Based on genetic and biochemical evidences, we herein clarify that the P450 enzyme StvP2 catalyzes the MDB formation in streptovaricins, with an atypical substrate inhibition kinetics. Furthermore, X-ray crystal structures in complex with substrate and structure-based mutagenesis reveal the intrinsic details of the enzymatic reaction. The mechanism of MDB formation is proposed to be an intramolecular nucleophilic substitution resulting from the hydroxylation by the heme core and the keto-enol tautomerization via a crucial catalytic triad (Asp89-His92-Arg72) in StvP2. In addition, in vitro reconstitution uncovers that C6-O-methylation and C4-O-acetylation of streptovaricins are necessary prerequisites for the MDB formation. This work provides insight for the MDB formation and adds evidence in support of the functional versatility of P450 enzymes., Streptovaricin C is an antibiotic containing a methylenedioxy bridge (MDB) moiety essential for its activity. Here, the authors show that a P450 monooxygenase StvP2 catalyses MDB formation, report its crystal structure in complex with the substrate, and elucidate mechanistic details of MDB formation.

Two new spirotetronate natural products, lobophorin L (1) and lobophorin M (2), together with three known lobophorin-like spirotetronate antibiotics (3–5) and two known ansamycins (6–7), were isolated from the marine-derived Streptomyces sp. 4506. The structures of 1 and 2 were established on the basis of HRESIMS as well as 1D and 2D NMR datasets. Antibacterial assay showed that, compounds 1 and 3–5 exhibited strong to moderate antibacterial activities against Micrococcus luteus and Bacillus thuringiensis with MIC values ranging from 0.0625 to 8 μg/mL, while compounds 3 and 6 showed weak antibacterial activities against Staphylococcus aureus and MRSA. The antibacterial activities of the lobophorins in this study indicated that the more substitution number of the sugar moieties at C-9 of the lobophorin, the stronger antimicrobial properties it may deserve, and the higher the oxidation degree of substituent group at C-3D, the better antibacterial activities of its corresponding compound could be.

Rechargeable aqueous Zn-ion battery has been considered as a key complement to the existing battery technologies due to its intrinsic merits such as operational safety and cost saving. However, issues of dendrite growth and accompanied water consumption hinder its further development. In this work, we utilize a chelating agent, 2-Bis(2-hydroxyethyl) amino-2-(hydroxymethyl)-1,3-propanediol (BIS-TRIS), to regulate the solvation sheath structure of Zn2+. Benefiting from such zinc-chelating coordination, Zn2+ 2D diffusion can be restricted and the altered deposition kinetic has contributed to the inhibition of the dendrite growth. In addition, partial substitution of water in solvation shell with chelator can also greatly suppress the competitive hydrogen evolution reaction (HER). Consequently, a stable symmetric Zn cell with lifetime more than 1000 h at a current density of 1 mA cm−2 is achieved. Moreover, the aqueous Zn/MnO2 battery with BIS-TRIS as electrolyte additive delivers an 86% capacity retention after 600 cycles at 500 mA g−1. This zinc-chelating coordination based facile strategy opens a new window for the future development in dendrite-free Zn anode.

A bioassay‐guided fractionation led to the isolation of hangtaimycin (HTM) from Streptomyces spectabilis CCTCC M2017417 and the discovery of its hepatoprotective properties. Structure elucidation by NMR suggested the need for a structural revision. A putative HTM degradation product was also isolated and its structure was confirmed by total synthesis. The biosynthetic gene cluster was identified and resembles a hybrid trans‐AT PKS/NRPS biosynthetic machinery whose first PKS enzyme contains an internal dehydrating bimodule, which is usually found split in other trans‐AT PKSs. The mechanisms of such dehydrating bimodules have often been proposed, but have never been deeply investigated. Here we present in vivo mutations and in vitro enzymatic experiments that give first and detailed mechanistic insights into catalysis by dehydrating bimodules., Hangtaimycin biosynthesis proceeds through a hybrid trans‐AT PKS/NRPS biosynthetic machinery that contains distinctive dehydrating bimodules. Here we present detailed mechanistic insights into catalysis by dehydrating bimodules that are generally involved in the biosynthesis of polyketides with Z double bonds. This work lays the foundations for future structural modifications by protein engineering.

Four new hydroxamate-containing natural product cyclopeptides designated acremonpeptides A-D (1-4), together with Al(III)-acremonpeptide D (5) were obtained from the marine fungus Acremonium persicinum SCSIO 115. The planar structures of 1-5 were established on the basis of HRMS as well as 1D and 2D NMR data sets. Moreover, the amino acid absolute configurations were determined using Marfey's method. Compounds 1-5 all feature three 2-amino-5-(N-hydroxyacetamido)pentanoic acid (N5-hydroxy-N5-acetyl-l-ornithine) metal ion chelating moieties. Beyond their discovery and structure elucidation, in vitro bioassays revealed acremonpeptides A (1), B (2), and Al(III)-acremonpeptide D (5) as moderate antiviral agents for herpes simplex virus 1 with EC50 values of 16, 8.7, and 14 μM, respectively.

Abstarct An ultra-narrow-band perfect absorber based on collective resonances in an Ag nanoring period array is theoretically proposed for the absorption enhancement of monolayer graphene, where the absorptivity can reach as high as 99.4% with the full-width-half-maximum as narrow as 3.6 nm in the visible band. This outstanding absorptive characteristic can be attributed to the excitation of surface lattice resonance modes by Ag nanoring periodic array. The as-designed structure possesses high refractive-index sensitivity, reaching 557.9 nm RIU−1 with its figure of merit attaining 155 RIU−1. This work provides promising guidance for developing high-performance graphene-based photonic devices.

Two new ansamycin derivatives, damavaricin H (

Two new ansamycin derivatives, damavaricin H (1) and protostreptovaricin VI (2) were isolated from the Streptomyces spectabilis CCTCC M2017417 derived mutants of ΔstvP5 and ΔstvA2, respectively. The structures of 1 and 2 were established by analysis of the HRESIMS as well as 1D and 2D NMR datasets. The minimum inhibitory concentration (MIC) results showed that compounds 1 and 2 possessed the corresponding anti-MRSA bioactivities of 4 ∼ 8 μg/ml and 8 ∼ 16 μg/ml, which confirmed the structure-activity relationships of streptovaricins reported previously and also revealed that addition of the hydroxyl group at C-8 increased the anti-MRSA activity.

Two new spirotetronate natural products, lobophorin L (

The ether extract ofArtemisia integrifoliawas separated by chromatography and afforded a new iridoid, arteintegin A (6), together with five known compounds, namely chamazulene (1) , acetylenes (E)-2, (E)-3, (Z)-4, eugenol (5). The structure elucidation of the new compound was carried out by 1D ( 1H NMR and 13C NMR) and 2D-NMR (COSY, HSQC and NOESY) spectral analysis .

In this work, garnet-framework Li3Nd3W2O12 as a novel insertion-type anode material has been prepared via a facile sol–gel method and examined as a lithium container for lithium ion batteries (LIBs...

Despite the impressive merits of low-cost and high-safety electrochemical energy storage for aqueous zinc ion batteries, researchers have long struggled against the unresolved issues of dendrite growth and the side reactions of zinc metal anodes. Herein, a new strategy of zinc-electrolyte interface charge engineering induced by amino acid additives is demonstrated for highly reversible zinc plating/stripping. Through electrostatic preferential absorption of positively charged arginine molecules on the surface of the zinc metal anode, a self-adaptive zinc-electrolyte interface is established for the inhibition of water adsorption/hydrogen evolution and the guidance of uniform zinc deposition. Consequently, an ultra-long stable cycling up to 2200 h at a high current density of 5 mA cm−2 is achieved under an areal capacity of 4 mAh cm−2. Even cycled at an ultra-high current density of 10 mA cm−2, 900 h-long stable cycling is still demonstrated, demonstrating the reliable self-adaptive feature of the zinc-electrolyte interface. This work provides a new perspective of interface charge engineering in realizing highly reversible bulk zinc anode that can prompt its practical application in aqueous rechargeable zinc batteries.

The preparation and characterization of Pb1-xBaxLi2Ti6O14 (x = 0, 1/4, 1/2, 3/4, 1) as anode materials for lithium ion batteries are investigated in this research. The structure, morphology and electrochemical properties are compared with each other by changing the Pb/Ba atomic ratio in Pb1-xBaxLi2Ti6O14. It can be observed that each sample shows the same orthorhombic structure with Cmca space group. Moreover, it can also be found that the working potential, conductivity, cycling and rate performances of as-received samples gradually change along with the evolution of x in Pb1-xBaxLi2Ti6O14 (x = 0, 1/4, 1/2, 3/4, 1). Electrochemical evaluation shows that the operating potential of the as-received sample gradually decreases with increasing x value in Pb1-xBaxLi2Ti6O14 and its initial charge capacity increases reversely. Moreover, different Pb/Ba atomic ratio also brings different cycling stability for Pb1-xBaxLi2Ti6O14. Especially for Pb3/4Ba1/4Li2Ti6O14, it presents better electrochemical properties than other samples. After 120 cycles, the reversible capacity of Pb3/4Ba1/4Li2Ti6O14 is maintained at 129.7 mAh g−1 with capacity retention of 88.3%. In addition, its electrochemical reversibility is also demonstrated by in-situ X-ray investigation.

Emodacidamides A–H (1–8), natural products featuring anthraquinone–amino acid conjugates, have been isolated from a marine-derived fungus, Penicillium sp. SCSIO sof101, together with known anthraquinones 9 and 10. The planar structures of 1–8 were elucidated using a combination of NMR spectroscopy and mass spectrometry. The absolute configurations of the amino acid residues were confirmed using Marfey’s method and chiral-phase HPLC analyses. Additionally, isolates were evaluated for possible immunomodulatory and cytotoxic activities. Emodacidamides A (1), C (3), D (4), and E (5) inhibited interleukin-2 secretion from Jurkat cells with IC50 values of 4.1, 5.1, 12, and 5.4 μM, respectively.

Isostructural LiMTiO 4 (M = Mn, Fe, Co) have been successfully synthesized by a facile sol-gel route and evaluated their possibility as an anode materials for lithium ion batteries (LIBs). All the samples exhibit high operating potential plateaus (>1.7 V vs. Li + /Li), which can prevent the formation of the solid electrolyte interphase (SEI) film on the electrode surface effectively. In addition, electrochemical investigations show that LiCoTiO 4 has a superior cycling performance, better rate capability, lower charge transfer resistance and higher lithium-ion diffusion coefficient than those of LiMnTiO 4 and LiFeTiO 4 . These electrochemical results indicate that LiCoTiO 4 is the most promising lithium storage material among all the examined spinel-type LiMTiO 4 samples.

Metal doping is an effective way to improve the electrochemical properties of titanates. In this work, Ba-site substituted Ba 0.9 M 0.1 Li 2 Ti 6 O 14 (M = K, Zn, La) are synthesized to fabricate high performance titanate anode for lithium-ion batteries. Electrochemical evaluations reveal that introducing metal doping at Ba-site can result in higher ionic/electronic conductivity. As a result, Ba 0.9 M 0.1 Li 2 Ti 6 O 14 exhibits enhanced lithium storage capability. Especially for Ba 0.9 La 0.1 Li 2 Ti 6 O 14 , it shows the best electrochemical performance with a high reversible charge capacity of 151.3 mAh g −1 and high capacity retention of 94.21% at a current density of 100 mA g −1 . For comparison, the pristine BaLi 2 Ti 6 O 14 only exhibits a reversible charge capacity of 128.5 mAh g −1 with the capacity retention of 80.06% after 100 cycles. Further, the lithium storage process is investigated in detail by in-situ structural observation, which reveals a maximum volume expansion of 1.9% for Ba 0.9 La 0.1 Li 2 Ti 6 O 14 during charge-discharge cycle. It shows that Ba 0.9 La 0.1 Li 2 Ti 6 O 14 is a possible material with high structural reversibility for lithium storage.

In order to investigate the lithiation-delithiation kinetics in BaLi2Ti6O14 anode material, BaLi2Ti6O14 is achieved by a solid-state reaction process in this work. The as-prepared BaLi2Ti6O14 is high purity titanate and well crystallized with a particle size distribution in the range of 0.5–1.5 μm. Electrochemical analysis shows that BaLi2Ti6O14 can deliver a reversible capacity of 126.1 mAh g− 1 at 5C, and the capacity retention is 74.1% after 1000 cycles. In addition, the electrochemical kinetics of BaLi2Ti6O14 is investigated by cyclic voltammetry (CV), in-situ electrochemical impedance spectroscopy (in-situ EIS) and galvanostatic intermittent titration (GITT) techniques. The DLi + values calculated from CVs are located in the range of 10− 13–10− 12 cm2 s− 1. For comparison, the average DLi + values received from EIS and GITT methods are located in the range of 10− 14–10− 12 cm2 s− 1 and 10− 14–10− 11 cm2 s− 1, respectively. Although the DLi + differs by several orders of magnitude from different measurement techniques, it still reveals higher value than that of Li4Ti5O12. Owing to the rapid diffusion kinetics of BaLi2Ti6O14, symmetrical structural evolutions can be observed via in-situ X-ray diffraction (XRD) study, which indicates that BaLi2Ti6O14 is a promising high-power anode candidate.

Four new hydroxamate-containing natural product cyclopeptides designated acremonpeptides A-D (

Mycophenolic acid (MPA) is a group of metabolite derived from several species of

Mycophenolic acid (MPA) is a group of metabolite derived from several species of Penicillium, which shows potent bioactivity. In this study, a new derivative of MPA compound named penicacid D (1), was isolated from the marine derived fungus Penicillium sp. SCSIO sof101, along with seven known compounds (2-8). Their structures were elucidated based on the HR-ESI-MS and NMR data. Moreover, the 1H and 13C NMR data of compound 2 and the 13C NMR data of compound 3 are reported. Compounds 1, 4 and 6 exhibited weak activities against Escherichia coli (clinical isolation number 100385570) and Acinetobacter baumannii (clinical isolation number 100069).

In the face of high cost and insufficient energy density of current lithium ion batteries, aqueous rechargeable Zn-air batteries with the advantages of low cost, environmental benignity, safety and high energy density are spotlighted in recent years. The practical application of Zn-air batteries, however, is severely restricted by the high overpotential, which is associated with the inherent sluggish kinetics of oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) of air electrocatalysts. Recently, engineering heterostructured/hybrid electrocatalysts by modulating the interface chemistry has been demonstrated as an effective strategy to improve the catalytic performance. Basically, there occur significant electronic effect, geometric effect, coordination effect, synergistic effect, and confinement effect at the heterostructure interface, which intensely affect electrocatalysts’ performance in terms of intrinsic activity, active site density and durability. In this review, the recent progress on development of heterostructured air electrocatalysts by interface engineering is summarized. Particularly, the potential relationship between interface chemistry and oxygen electrocatalysis kinetics is bridged and outlined. This review would provide a comprehensive and in-depth understanding of the crucial role of the well-defined interfaces towards fast oxygen electrocatalysis, and would offer a solid scientific basis for the rational design of efficient heterostructured air electrocatalysts and beyond.

Spinel LiCrTiO4 is synthesized via sol-gel pretreatment and subsequent solid state reaction at different calcining temperatures. Structural observation and electrochemical evaluation show that 800 °C is a suitable calcining temperature for LiCrTiO4 preparation. Compared with samples prepared at other temperatures, LiCrTiO4 formed at 800 °C exhibits better electrochemical performance with the capacity retention of 92.2% at 100 mA g−1 after 80 cycles. Even cycled at a higher current density of 500 mA g−1 in 0.0-3.0 V, LiCrTiO4 prepared at 800 °C still shows excellent cycling performance with a reversible capacity of 226.7 mAh g−1 after 80 cycles. Ex-situ valence analysis reveals that the high lithium storage capacity in LiCrTiO4 between 0.0 and 3.0 V is attributed to the reversible redox process of Ti4+/Ti3+ and Cr3+/Cr2+ couples. In addition, quasi zero-strain characteristic of LiCrTiO4 during lithiation is also demonstrated by in-situ and ex-situ structural observations. Therefore, LiCrTiO4 exhibits high structural stability and electrochemical reversibility as anode material for rechargeable lithium-ion batteries.

By using a simple high temperature solid state reaction, LiNi0.6Co0.2Mn0.1Al0.1O2 is prepared via Ni site dual substitution with Mn and Al. Structural observation reveals that the as-prepared sample can be indexed to an α-NaFeO2 type single phase with R-3m space group. Morphology and particle size investigations present that Mn and Al co-doped LiNi0.8Co0.2O2 is composed of micro-sized secondary particles (5–20 μm) agglomerated from highly packed primary particles (1–2 μm). Charge–discharge tests demonstrate that LiNi0.6Co0.2Mn0.1Al0.1O2 can reversibly react with lithium between 2.5 and 4.9 V with a high discharge capacity of 202.0 mAh g−1. This favorable electrochemical performance is attributed to the stable crystal structure after Mn and Al dual doping. This quasi-reversible structural change is also proved by in-situ X-ray diffraction study in this work.

In consideration of the abundance of sodium resources, sodium ion batteries (SIBs) have been revisited recently and are considered as a substitution for lithium ion batteries (LIBs). Among all the proposed anodes for SIBs, metal selenides labeled as high theoretical capacity materials have aroused the interest of battery researchers. However, as conversion/alloying based electrode materials, metal selenides suffer from a severe volume change during cycling, thus leading to kinetic problems and poor electrochemical stability, which restrain their further application in SIBs. Therefore, modification strategies such as coupling with carbonaceous material, designing unique structure, selecting an upper cut-off voltage, optimizing the composition of electrolyte, controlling the composition of the material etc. have been adopted to alleviate the volume change issue of metal selenides electrodes. In this article, the research progresses on the metal selenides as electrodes for SIBs are comprehensively reviewed and the difference and necessity of each metal selenide from the perspectives of structure and conductivity are emphasized. The summarization of metal selenides contains the synthesis methods, modification methods for performance improvement, corresponding reaction mechanism and performance in full-cell system. Finally, a conclusion with the challenges and outlook of metal selenides in the field of SIBs is also presented.

In this work, garnet-framework Li

Additional file 1. Fig. S1. MALDI-TOFâ MS spectrum of eBSA. Fig. S2. A working curve for quantification of HA content in HA-eNPs using Alcian blue assay. Fig. S3 Difference on expression of CD44 between B16F10 and MCF-7 cells. Fig. S4 In vitro antitumor effects of NP formulations on the MCF-7 cells. Fig. S5. Time-dependent intensity of fluorescence distribution of eNPs in mouse. Fig. S6. HA-eNPs/ATRA reduced the tumorigenicity of CD44-enriched B16F10 cells.

The gene cluster responsible for grincamycin (GCN, 1) biosynthesis in Streptomyces lusitanus SCSIO LR32 was identified; heterologous expression of the GCN cluster in S. coelicolor M512 yielded P-1894B (1b) as a predominant product. The Delta gcnQ mutant accumulates intermediate la and two shunt products 2a and 3a bearing L-rhodinose for L-cinerulose A substitutions. In vitro data demonstrated that GcnQ is capable of iteratively tailoring the two L-rhodinose moieties into L-aculose moieties, supporting divergent roles of GcnQ in different hosts.

[Song, Xianqin; Luo, Minghe; Lu, Laichun] Third Mil Med Univ, Coll Pharm, Teaching Expt Ctr, Chongqing 400038, Peoples R China; Qingdao Univ, Affiliated Hosp, Cent Lab, 1677 Wutaishan Rd, Qingdao 266003, Peoples R China; [Huang, Hongbo] Chinese Acad Sci, South China Sea Inst Oceanol, RNAM Ctr Marine Microbiol, CAS Key Lab Trop Marine Bioresources & Ecol,Guand, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China

A new diketopiperazine (DKP) derivative, (6R,3Z)-3-benzylidene-6-isobutyl-1-methyl piperazine-2,5-dione (1), as well as five known DKPs 2–6 was isolated from a deep sea-derived Streptomyces sp. SCSIO 04496. The structure of 1 was elucidated using a combination of 1D and 2D NMR, HR-ESI-MS and chiral-phase HPLC techniques. Compounds 1–6 did not show cytotoxic activity at a concentration of 100 μM in bioactivity assay.

9-Methylstreptimidone is a glutarimide antibiotic showing antiviral, antifungal, and antitumor activities. Genome scanning, bioinformatics analysis, and gene inactivation experiments reveal a gene cluster responsible for the biosynthesis of 9-methylstreptimidone in Streptomyces himastatinicus. The unveiled machinery features both acyltransferase- and thioesterase-less iterative use of module 5 as well as a branching module for glutarimide generation. Impressively, inactivation of smdK leads to a new carboxylate analogue unveiling a new mechanism for polyketide terminal diene formation.

Marinactinospora thermotolerans SCSIO 00652, originating from a deep-sea marine sediment of the South China Sea, was discovered to produce antimicrobial nucleoside antibiotic A201A. Whole-genome scanning and annotation strategies enabled us to localize the genes responsible for A201A biosynthesis and to experimentally identify the gene cluster; inactivation of mtdF , an oxidoreductase gene within the suspected gene cluster, abolished A201A production. Bioinformatics analysis revealed that a gene designated mtdA furthest upstream within the A201A biosynthetic gene cluster encodes a GntR family transcriptional regulator. To determine the role of MtdA in regulating A201A production, the mtdA gene was inactivated in frame and the resulting Δ mtdA mutant was fermented alongside the wild-type strain as a control. High-performance liquid chromatography (HPLC) analyses of fermentation extracts revealed that the Δ mtdA mutant produced A201A in a yield ∼25-fold superior to that of the wild-type strain, thereby demonstrating that MtdA is a negative transcriptional regulator governing A201A biosynthesis. By virtue of its high production capacity, the Δ mtdA mutant constitutes an ideal host for the efficient large-scale production of A201A. These results validate M. thermotolerans as an emerging source of antibacterial agents and highlight the efficiency of metabolic engineering for antibiotic titer improvement.