The microstructure evolution and high-temperature mechanical properties of laser beam welded TC4/TA15 dissimilar titanium alloy joints under different welding parameters were studied.The results show that the weld fus...The microstructure evolution and high-temperature mechanical properties of laser beam welded TC4/TA15 dissimilar titanium alloy joints under different welding parameters were studied.The results show that the weld fusion zone of TC4/TA15 dissimilar welded joints consists of coarsenedβcolumnar crystals that contain mainly acicularα’martensite.The heat affected zone is composed of the initialαphase and the transformedβstructure,and the width of heat affected zone on the TA15 side is narrower than that on the TC4 side.With increasing temperature,the yield strength and ultimate tensile strength of the TC4/TA15 dissimilar welded joints decrease and the highest plastic deformation is obtained at 800°C.The tensile strength of the dissimilar joints with different welding parameters and base material satisfies the following relation(from high to low):TA15 base material>dissimilar joints>TC4 base material.The microhardness of a cross-section of the TC4/TA15 dissimilar joints reaches a maximum at the centre of the weld and is reduced globally after heat treatment,but the microhardness distribution is not changed.An elevated temperature tensile fracture of the dissimilar joints is located on the side of the TC4 base material.Necking occurs during the tensile tests and the fracture characteristics are typical when ductility is present in the material.展开更多
Friction stir welding (FSW) with water cooling and air cooling was used to weld 2219-T62 aluminum alloy joints with a thickness of 20 mm. The effect of cooling conditions on the corrosion resistance of joints in 3.5% ...Friction stir welding (FSW) with water cooling and air cooling was used to weld 2219-T62 aluminum alloy joints with a thickness of 20 mm. The effect of cooling conditions on the corrosion resistance of joints in 3.5% NaCl solution was investigated using the open circuit potential (OCP), the potentiodynamic polarization, and the corrosion morphology after immersing for different time. And the precipitates distribution was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results reveal that the weld nugget zone (WNZ) owning positive potential, lower corrosion current density and fine and uniform precipitates, is much more difficult to corrode than the heat affected zone (HAZ) and the base metal (BM). Compared with air-cooled joint, the water-cooled joint has better corrosion resistance. In addition, the results of microstructure observation show that the potential, distribution and size of second phase particles determine the corrosion resistance of FSW AA2219 alloy joints in chlorine-contained solution.展开更多
The microstructure and mechanical properties of laser beam welded dissimilar joints in TC4 and TA15 titanium alloyswere investigated. The results showed that the coarse columnar grains containing a large amount of aci...The microstructure and mechanical properties of laser beam welded dissimilar joints in TC4 and TA15 titanium alloyswere investigated. The results showed that the coarse columnar grains containing a large amount of acicular α and martensite α′ werepresent in the fusion zone (FZ), some residual α phases and martensite structure were formed in the heat-affected zone (HAZ) onTC4 side, and bulk equiaxed α phase of the HAZ was on TA15 side. An asymmetrical microhardness profile across the dissimilarjoint was observed with the highest microhardness in the FZ and the lowest microhardness in TA15 BM. The orders of yield strengthand ultimate tensile strength were as follows: TC4 BM > TC4/TC4 similar joint > TA15 BM > TA15/TA15 similar joint > TC4/TA15dissimilar joint, and increased while hardening capacity and strain hardening exponent decreased with increasing strain rate from1×10?4 s?1 to 1×10?2 s?1. The TC4/TA15 dissimilar joints failed in the TA15 BM, and had characteristics of ductile fracture atdifferent strain rates.展开更多
BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative ...BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative complications which needs immediate recognition.On the other hand,as a rheumatological disease,lupus nephritis requires a long period of hormone therapy.Cases of pneumothorax in hormone-consuming renal cancer patients are even fewer.CASE SUMMARY A 39-year-old woman was admitted to our department to take a laparoscopic partial nephrectomy.The patient had a medical history of lupus nephritis and renal clear cell carcinoma with hormone and target treatment.Her blood oxygen saturation dropped to 92%during the operation,and pneumothorax was detected by ultrasound.O2 inhalation and lung dilation were performed.Her vital signs were monitored closely throughout the operation.The operation was accomplished,and she regained consciousness smoothly.A postoperative bedside chest X-ray was conducted after she was transferred to the urosurgery ward,while no evidence of further pneumothorax or lib injury was observed.CONCLUSION Pneumothorax is a severe complication in laparoscopic or robotic-assisted laparoscopic operations,especially in retroperitoneal ones.It is easily neglected unless the injury of the diaphragm is found.Low insufflation pressure and shorter operation time are necessary for patients with a history of long-term hormone consumption or chronic immune system disease.展开更多
Proanthocyanidins （PAs） as the end products of flavonoid biosynthetic pathway mainly accumulate in seed coat but their biological function is largely unknown. We studied the anti-oxidation ability in seed coat and g...Proanthocyanidins （PAs） as the end products of flavonoid biosynthetic pathway mainly accumulate in seed coat but their biological function is largely unknown. We studied the anti-oxidation ability in seed coat and germination changes under externally applied oxidative stresses in PAs-deficient mutants of Arabidopsis. Germination of PAs-deficient mutant seeds was faster than that of wild-type under low or no oxidative stress, suggesting a PAs-induced inhibition of germination. When the applied oxidative stress was high, germination of PAs-deficient mutants was lower than that of wild-type, suggesting a loss of PAs-related anti-oxidation ability in the mutants. Using ABA signaling mutants, our studies demonstrated that both ABA signaling pathway and PAs were important for the response to serve oxidative stress during seed germination. However, the discrepancy of the response between abi mutants and PAs mutants to oxidative stress suggests that ABA signaling pathway may not play a major role in PAs＂ action in alleviating oxidative stress. Under low or no oxidative stress, germination was mainly determined by the ABA content in seed and the PAs-deficient mutant seeds germinated faster due to their lower ABA content than wild-type. However, oxidative injury inhibited germination when PAs-deficient seeds germinated under high oxidative stress, Wild-type exhibited higher germination under the high ox- idative stress due to the PAs＇ anti-oxidation ability. Oxidative stress applied externally led to changes in endogenous PAs contents that coincided with the expression changes of PAs biogenesis genes. PAs modulated the activities of some key enzymes that controlled the levels of reactive oxygen species and the anti-oxidation capacity during the seed germination. This work suggests that PAs contribute to the adaptive mechanism that helps germination under environmental stresses by playing dual roles in both germination control and anti-oxidation reaction.展开更多
Marine natural products play critical roles in the chemical defense of many marine organisms and are essential,reputable sources of successful drug leads.Sixty-seven 14-membered resorcylic acid lactone derivatives 3–...Marine natural products play critical roles in the chemical defense of many marine organisms and are essential,reputable sources of successful drug leads.Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol(1)isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination,acylation,esterification,and acetalization in one to three steps.The structures of these new derivatives were established by HRESIMS and NMR techniques.All the compounds(1–71)were evaluated for their antialgal and antiplasmodial activities.Among them,14 compounds displayed antifouling activities against adhesion of the fouling diatoms.In particular,9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua(EC50=6.67 and 8.55μmol/L),respectively,which were similar in efficacy to those of the positive control SeaNine 211(EC50=2.90 and 9.74μmol/L).More importantly,38,39,and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72μmol/L.Very interestingly,the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model,thus,representing potential promising antiplasmodial drug agents.The preliminary structure–activity relationships indicated that biphenyl substituent at C-2,acetonide at positions C-5′and C-6′,and tri-or tetra-substituted of acyl groups increased the antiplasmodial activity.Therefore,combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy,not only for environmentally friendly antifoulants but also for structurally novel drugs.展开更多
Multidrug resistance(MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein(P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we repor...Multidrug resistance(MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein(P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp,WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel(PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4(CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft(PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.展开更多
Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,...Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.展开更多
Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant...Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.展开更多
基金Project(51405392)supported by the National Natural Science Foundation of ChinaProject(2019T120954)supported by the China Postdoctoral Science Foundation+1 种基金Project(2018BSHQYXMZZ31)supported by the Shaanxi Provincial Postdoctoral Science Foundation,ChinaProject(3102019MS0404)supported by the Fundamental Research Funds for the Central Universities,China.
文摘The microstructure evolution and high-temperature mechanical properties of laser beam welded TC4/TA15 dissimilar titanium alloy joints under different welding parameters were studied.The results show that the weld fusion zone of TC4/TA15 dissimilar welded joints consists of coarsenedβcolumnar crystals that contain mainly acicularα’martensite.The heat affected zone is composed of the initialαphase and the transformedβstructure,and the width of heat affected zone on the TA15 side is narrower than that on the TC4 side.With increasing temperature,the yield strength and ultimate tensile strength of the TC4/TA15 dissimilar welded joints decrease and the highest plastic deformation is obtained at 800°C.The tensile strength of the dissimilar joints with different welding parameters and base material satisfies the following relation(from high to low):TA15 base material>dissimilar joints>TC4 base material.The microhardness of a cross-section of the TC4/TA15 dissimilar joints reaches a maximum at the centre of the weld and is reduced globally after heat treatment,but the microhardness distribution is not changed.An elevated temperature tensile fracture of the dissimilar joints is located on the side of the TC4 base material.Necking occurs during the tensile tests and the fracture characteristics are typical when ductility is present in the material.
基金Project (51405392) supported by the National Natural Science Foundation of ChinaProject (2019T120954) supported by the China Postdoctoral Science Foundation+1 种基金Project (3102019MS0404) supported by Fundamental Research Funds for the Central Universities, ChinaProject (2018BSHQYXMZZ31) supported by the Postdoctoral Science Foundation of Shaanxi Province, China。
文摘Friction stir welding (FSW) with water cooling and air cooling was used to weld 2219-T62 aluminum alloy joints with a thickness of 20 mm. The effect of cooling conditions on the corrosion resistance of joints in 3.5% NaCl solution was investigated using the open circuit potential (OCP), the potentiodynamic polarization, and the corrosion morphology after immersing for different time. And the precipitates distribution was characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results reveal that the weld nugget zone (WNZ) owning positive potential, lower corrosion current density and fine and uniform precipitates, is much more difficult to corrode than the heat affected zone (HAZ) and the base metal (BM). Compared with air-cooled joint, the water-cooled joint has better corrosion resistance. In addition, the results of microstructure observation show that the potential, distribution and size of second phase particles determine the corrosion resistance of FSW AA2219 alloy joints in chlorine-contained solution.
基金Project(51405392)supported by the National Natural Science Foundation of ChinaProject(20136102120022)supported by the Research Fund for the Doctoral Program of Higher Education of ChinaProject(3102015ZY023)supported by the Fundamental Research Funds for the Central Universities,China
文摘The microstructure and mechanical properties of laser beam welded dissimilar joints in TC4 and TA15 titanium alloyswere investigated. The results showed that the coarse columnar grains containing a large amount of acicular α and martensite α′ werepresent in the fusion zone (FZ), some residual α phases and martensite structure were formed in the heat-affected zone (HAZ) onTC4 side, and bulk equiaxed α phase of the HAZ was on TA15 side. An asymmetrical microhardness profile across the dissimilarjoint was observed with the highest microhardness in the FZ and the lowest microhardness in TA15 BM. The orders of yield strengthand ultimate tensile strength were as follows: TC4 BM > TC4/TC4 similar joint > TA15 BM > TA15/TA15 similar joint > TC4/TA15dissimilar joint, and increased while hardening capacity and strain hardening exponent decreased with increasing strain rate from1×10?4 s?1 to 1×10?2 s?1. The TC4/TA15 dissimilar joints failed in the TA15 BM, and had characteristics of ductile fracture atdifferent strain rates.
文摘BACKGROUND Downgrading target treatment and laparoscopic partial nephrectomy have become increasingly popular in patients with renal cell carcinomas.Rare as it is,pneumothorax is one of the most severe intraoperative complications which needs immediate recognition.On the other hand,as a rheumatological disease,lupus nephritis requires a long period of hormone therapy.Cases of pneumothorax in hormone-consuming renal cancer patients are even fewer.CASE SUMMARY A 39-year-old woman was admitted to our department to take a laparoscopic partial nephrectomy.The patient had a medical history of lupus nephritis and renal clear cell carcinoma with hormone and target treatment.Her blood oxygen saturation dropped to 92%during the operation,and pneumothorax was detected by ultrasound.O2 inhalation and lung dilation were performed.Her vital signs were monitored closely throughout the operation.The operation was accomplished,and she regained consciousness smoothly.A postoperative bedside chest X-ray was conducted after she was transferred to the urosurgery ward,while no evidence of further pneumothorax or lib injury was observed.CONCLUSION Pneumothorax is a severe complication in laparoscopic or robotic-assisted laparoscopic operations,especially in retroperitoneal ones.It is easily neglected unless the injury of the diaphragm is found.Low insufflation pressure and shorter operation time are necessary for patients with a history of long-term hormone consumption or chronic immune system disease.
文摘Proanthocyanidins （PAs） as the end products of flavonoid biosynthetic pathway mainly accumulate in seed coat but their biological function is largely unknown. We studied the anti-oxidation ability in seed coat and germination changes under externally applied oxidative stresses in PAs-deficient mutants of Arabidopsis. Germination of PAs-deficient mutant seeds was faster than that of wild-type under low or no oxidative stress, suggesting a PAs-induced inhibition of germination. When the applied oxidative stress was high, germination of PAs-deficient mutants was lower than that of wild-type, suggesting a loss of PAs-related anti-oxidation ability in the mutants. Using ABA signaling mutants, our studies demonstrated that both ABA signaling pathway and PAs were important for the response to serve oxidative stress during seed germination. However, the discrepancy of the response between abi mutants and PAs mutants to oxidative stress suggests that ABA signaling pathway may not play a major role in PAs＂ action in alleviating oxidative stress. Under low or no oxidative stress, germination was mainly determined by the ABA content in seed and the PAs-deficient mutant seeds germinated faster due to their lower ABA content than wild-type. However, oxidative injury inhibited germination when PAs-deficient seeds germinated under high oxidative stress, Wild-type exhibited higher germination under the high ox- idative stress due to the PAs＇ anti-oxidation ability. Oxidative stress applied externally led to changes in endogenous PAs contents that coincided with the expression changes of PAs biogenesis genes. PAs modulated the activities of some key enzymes that controlled the levels of reactive oxygen species and the anti-oxidation capacity during the seed germination. This work suggests that PAs contribute to the adaptive mechanism that helps germination under environmental stresses by playing dual roles in both germination control and anti-oxidation reaction.
基金supported by the Program of National Natural Science Foundation of China(Nos.U1706210,41776141,42006092,41322037 and 41830535)the Fundamental Research Funds for the Central Universities(No.201841004)+2 种基金the Marine S&T Fund of Shandong Province for Pilot National Laboratory for Marine Science and Technology(Qingdao)(No.2018SDKJ0403-2)the Research Fund of State Key Laboratory for Marine Corrosion and Protection of Luoyang Ship Material Research Institute(LSMRI)[No.KF190402],and the Taishan Scholars Program,China(No.tsqn20161010)funded by a SENACYT grant(FID17-095)and partially by the National System of Investigators(SNI)of Panama.
文摘Marine natural products play critical roles in the chemical defense of many marine organisms and are essential,reputable sources of successful drug leads.Sixty-seven 14-membered resorcylic acid lactone derivatives 3–27 and 30–71 of the natural product zeaenol(1)isolated from the marine-derived fungus Cochliobolus lunatus were semisynthesized by chlorination,acylation,esterification,and acetalization in one to three steps.The structures of these new derivatives were established by HRESIMS and NMR techniques.All the compounds(1–71)were evaluated for their antialgal and antiplasmodial activities.Among them,14 compounds displayed antifouling activities against adhesion of the fouling diatoms.In particular,9 and 34 exhibited strong and selective inhibitory effects against the diatoms Navicula laevissima and Navicula exigua(EC50=6.67 and 8.55μmol/L),respectively,which were similar in efficacy to those of the positive control SeaNine 211(EC50=2.90 and 9.74μmol/L).More importantly,38,39,and 69–71 showed potent antiplasmodial activities against Plasmodium falciparum with IC50 values ranging from 3.54 to 9.72μmol/L.Very interestingly,the five antiplasmodial derivatives displayed non-toxicity in the cytotoxicity assays and the zebrafish embryos model,thus,representing potential promising antiplasmodial drug agents.The preliminary structure–activity relationships indicated that biphenyl substituent at C-2,acetonide at positions C-5′and C-6′,and tri-or tetra-substituted of acyl groups increased the antiplasmodial activity.Therefore,combining evaluation of chemical ecology with pharmacological models will be implemented as a systematic strategy,not only for environmentally friendly antifoulants but also for structurally novel drugs.
基金financial support from the National Natural Science Foundation of China (Nos.81973177,82103560 and 82103996)Medical Science and Technique Foundation of Henan Province (Nos.2018020486 and SB201901101,China)+5 种基金Science and Technique Foundation of Henan Province (Nos.202102310413,China)Natural Science Foundation of Henan Province (Nos.222300420069,212300410270 and 212300410253,China)1000 Talents Program of Central plains (No.204200510023,China)Young and Middleaged Health and Technology Innovation Leading Talent Project of Henan Province (No.YXKC2020008,China)Program for Science & Technology Innovation Talents in Universities of Henan Province (No.21HASTIT045,China)State Key Laboratory of Esophageal Cancer Prevention & Treatment (No.Z2020000X,China)。
文摘Multidrug resistance(MDR) is the main cause of clinical treatment failure and poor prognosis in cancer. Targeting P-glycoprotein(P-gp) has been regarded as an effective strategy to overcome MDR. In this work, we reported our preclinical studies of the triazolo[1,5-a]pyrimidine-based compound WS-716 as a highly potent, specific, and orally active P-gp inhibitor. Through direct binding to P-gp,WS-716 inhibited efflux function of P-gp and specifically reversed P-gp-mediated MDR to paclitaxel(PTX) in multiple resistant cell lines, without changing its expression or subcellular localization. WS-716 and PTX synergistically inhibited formation of colony and 3D spheroid, induced apoptosis and cell cycle arrest at G2/M phase in resistant SW620/Ad300 cells. In addition, WS-716 displayed minimal effect on the drug-metabolizing enzyme cytochrome P4503A4(CYP3A4). Importantly, WS-716 increased sensitivity of both pre-clinically and clinically derived MDR tumors to PTX in vivo with the T/C value of 29.7% in patient-derived xenograft(PDX) models. Relative to PTX treatment alone, combination of WS-716 and PTX caused no obvious adverse reactions. Taken together, our preclinical studies revealed therapeutic promise of WS-716 against MDR cancer, the promising data warrant its further development for cancer therapy.
基金This work was supported by the Program of National Natural Science Foundation of China(Nos.41906090,81874300,42006092,U1706210,41776141 and 41322037)the Program of Natural Science Foundation of Shandong Province of China(Nos.JQ201510 and ZR2019BD047)+1 种基金Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education,Hainan Normal University(RDZH2021003)the Taishan Scholars Program,China(No.tsqn20161010).
文摘Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides,namely,asperversiamides A–C(1–3)and asperheptatides A–D(4–7)and an unusual pyrroloindoline-containing new cycloheptapeptide,asperpyrroindotide A(8).The structure of 8 was elucidated by comprehensive spectroscopic data analysis,and its absolute configuration was determined by advanced Marfey’s method.The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized.Additionally,a series of new derivatives(10−19)of asperversiamide A(1)was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra.The preliminary structure−activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity.
基金This work was supported by National Natural Science Foundation of China(grant number 31730002,2170057)the National Key R&D Program of China(grant number 2019YFA09005400)。
文摘Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.
