A new compound of ansamitocin was isolated from the extracts of fermentation medium of mutant strain HGF052 derived from Actinosynnema pretiosum ssp. aurantium ATCC 31565, and identified as N-demethyl-desepoxy-9-methoxy-maytansinol (1) on the basis of extensive spectroscopic methods. Bioassay results showed that compound 1 had cytotoxic activity against HL-60 and BEL-7402 cell lines.
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http://dx.doi.org/10.1080/14786410902916552 | DOI Listing |
ACS Synth Biol
March 2024
State Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao 266237, China.
Currently, most maytansine-containing antibody-drug conjugates (ADCs) in clinical trials are prepared with DM1 or DM4, which in turn is synthesized mainly from ansamitocin P-3 (AP-3), a bacterial maytansinoid, isolated from . However, due to the high self-toxicity of AP-3 to , the yield of AP-3 has been difficult to improve. Herein, a new maytansinoid with much lower self-toxicity to , 3--carbamoylmaytansinol (CAM, ), was designed and generated by introducing the 3--carbamoyltransferase gene together with the -methyltransferase genes from exogenous maytansinoid gene clusters into the 3--acyltransferase gene () deleted mutant HGF052.
View Article and Find Full Text PDFCommun Biol
August 2023
State Key Laboratory of Microbial Metabolism, Shanghai-Islamabad-Belgrade Joint Innovation Center on Antibacterial Resistances, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.
Microbial bioactive natural products mediate ecologically beneficial functions to the producing strains, and have been widely used in clinic and agriculture with clearly defined targets and underlying mechanisms. However, the physiological effects of their biosynthesis on the producing strains remain largely unknown. The antitumor ansamitocin P-3 (AP-3), produced by Actinosynnema pretiosum ATCC 31280, was found to repress the growth of the producing strain at high concentration and target the FtsZ protein involved in cell division.
View Article and Find Full Text PDFBioengineering (Basel)
November 2022
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
is a well-known producer of maytansinoid antibiotic ansamitocin P-3 (AP-3). Growth of in submerged culture was characterized by the formation of complex mycelial particles strongly affecting AP-3 production. However, the genetic determinants involved in mycelial morphology are poorly understood in this genus.
View Article and Find Full Text PDFBioresour Bioprocess
August 2022
State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, China.
Ansamitocin P-3 (AP-3) produced by Actinosynnema pretiosum is a potent antitumor agent. However, lack of efficient genome editing tools greatly hinders the AP-3 overproduction in A. pretiosum.
View Article and Find Full Text PDFFront Microbiol
April 2022
Department of Epidemiology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
PhoPR is an important two-component signal transduction system (TCS) for microorganisms to sense and respond to phosphate limitation. Although the response regulator PhoP controls morphological development and secondary metabolism in various species, the function of PhoP in remains unclear. In this study, we showed that PhoP significantly represses the morphological development of the X47 strain.
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