Article
Biochemical Research Methods
Sina A. Stierle, Lauritz Harken, Shu-Ming Li
Summary: Cyclodipeptides from fungi and bacteria, which are often modified by different tailoring enzymes, have various biological and pharmacological activities. In this study, we used genetic engineering to design modified cyclodipeptides by incorporating gtmA core gene and gtmB-gtmE genes from the silent guatrypmethine gene cluster of Streptomyces cinnamoneus. Addition of different cyclodipeptides to the transformant led to the detection of diverse pathway products. Coexpression of CDPS genes from multiple Streptomyces strains with gtmB-gtmE resulted in the formation of diketopiperazine derivatives with varying modification stages. Our results demonstrate the potential of rational gene combination to increase structural diversity.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Anam Rubbab Pasha, Ajmal Khan, Saeed Ullah, Sobia Ahsan Halim, Javid Hussain, Muhammad Khalid, Muhammad Moazzam Naseer, Attalla F. El-kott, Sally Negm, Ahmed Al-Harrasi, Zahid Shafiq
Summary: This study synthesized Schiff bases of 1,3-dipheny urea and evaluated their anti-diabetic capability by inhibiting alpha-glucosidase. The compounds showed potent inhibition with IC50 values ranging from 2.14-115 mu M. Docking results indicated the important role of Glu277 and Asn350 in stabilizing these compounds at the active site of the enzyme. These molecules exhibited promising pharmacokinetics, physicochemical properties, and drug-likeness profile. The anti-diabetic potential of these compounds highlights their medical importance and potential therapeutic options for treating type II diabetes.
SCIENTIFIC REPORTS
(2023)
Article
Chemistry, Multidisciplinary
Mahendra Gowdru Srinivasa, Jagdish Gopal Paithankar, Sumit Rao Saheb Birangal, Aravinda Pai, Vasudev Pai, Shridhar N. Deshpande, B. C. Revanasiddappa
Summary: Hybrid molecules containing multiple biologically active functional groups have a greater affinity and efficiency compared to standard medicinal compounds. In this study, a combination of thiazolidinediones and 1,3,4-oxadiazoles was investigated for its potential enhancement of alpha-amylase and alpha-glucosidase inhibition activity. Novel derivatives were synthesized and characterized, and in silico and in vitro assays were performed to evaluate their inhibitory effects. The compounds showed promising inhibitory activity and could be further developed as a new class of antidiabetic agents.
Article
Biochemistry & Molecular Biology
Xuejun Lu, Manlai Zhang, Yixian Qiu, Xiuxiu Liu, Cancan Wang, Jianwei Chen, Huawei Zhang, Bin Wei, Yanlei Yu, Youmin Ying, Kui Hong, Hong Wang
Summary: AGS inhibitors derived from mangrove-derived actinomycetes were found to have inhibitory activity against alpha-glucosidase. Twenty-eight secondary metabolites were identified, including previously undescribed compounds and compounds never before reported in a marine-derived microorganism. Several of these compounds showed potent to moderate AGS inhibitory activity and were not cytotoxic to human normal hepatocytes.
Article
Plant Sciences
Jing Liu, Yiling Yang, Xiulan Xie, Shu-Ming Li
Summary: Heterologous expression of a cdps-p450 locus from Streptomyces sp. NRRL S-1521 led to the identification of a new guaninylated diketopiperazine, guanitrypmycin D1. The cytochrome P450 GutD1521 catalyzes the regiospecific transfer of guanine to C-2 of the indole ring of cyclo-(L-Trp-L-Tyr) via a C-C linkage, representing a new chemical transformation within this enzyme class. Furthermore, GutD1521 efficiently accepts several other tryptophan-containing cyclodipeptides or derivatives for regiospecific coupling with guanine, thus generating different guanitrypmycin analogs.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Chemistry, Medicinal
Geting Ye, Cuiying Huang, Jialin Li, Tao Chen, Jing Tang, Wenbin Liu, Yuhua Long
Summary: In this study, six new DIKETOPIPERAZINE alkaloids were isolated from the fungus Aspergillus sp. 16-5c, along with ten known alkaloids. Bioassay results revealed significant alpha-glucosidase inhibitory activity in compounds 1 and 9, moderate activity in compounds 3, 10, 11, and 15, while no compounds showed PTP1B enzyme inhibition activity.
Article
Biochemistry & Molecular Biology
Weidong Wang, Zenggen Liu, Fan Kong, Lixia He, Linghao Fang, Qingyan Shu
Summary: Tree peonies are known for their horticultural and medicinal properties, particularly their seeds which have recently gained attention for their metabolites and bioactivities. This study isolated phytochemicals from tree peony seed coats and found variations in polyphenolic content among different Paeonia species. It was discovered that certain phytochemical compounds could potentially be therapeutic agents for hyperglycemia and diabetes mellitus by inhibiting alpha-glucosidase.
Article
Plant Sciences
Jing Liu, Yiling Yang, Lauritz Harken, Shu-Ming Li
Summary: Heterologous expression of a three-gene cluster from Streptomyces aurantiacus led to the elucidation of the biosynthetic steps of streptoazine C. The prenyltransferase SasB showed high flexibility towards tryptophan-containing cyclodipeptides. This study provides potential use of enzymes with high substrate promiscuity for generating prenylated derivatives.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Multidisciplinary Sciences
Anshupriya Si, Thilina D. Jayasinghe, Radhika Thanvi, Donald R. Ronning, Steven J. Sucheck
Summary: A new inhibitor of a GH13 enzyme was identified, and its inhibition mechanism was elucidated through synthesis and structural analysis, which will have implications for designing more potent and selective inhibitors.
SCIENTIFIC REPORTS
(2021)
Article
Infectious Diseases
Dashan Zhang, Junbo Wang, Yongjian Qiao, Baixin Lin, Zixin Deng, Lingxin Kong, Delin You
Summary: Two new cyclodipeptide derivatives and seven known cyclodipeptides were isolated from Streptomyces 26D9-414 through genome mining. The structures of the new compounds were determined using NMR and ECD analysis, while biosynthetic gene clusters were identified through antiSMASH analysis. One of the newly discovered compounds showed comparable cytotoxicity to cisplatin against cancer cell lines.
Article
Biotechnology & Applied Microbiology
Yuqiao Zhang, Tingting Yao, Yuechen Jiang, Huayue Li, Weicheng Yuan, Wenli Li
Summary: Cyclodipeptide synthases (CDPSs) catalyze the formation of cyclodipeptides using aminoacylated tRNAs as substrates, with great potential in producing diverse 2,5-diketopiperazines (2,5-DKP5). Genome mining of Streptomyces leeuwenhoekii NRRL B-24963 uncovered a two-gene locus, saz, encoding CDPS SazA and a unique fused enzyme (SazB) with PT and MT domains. Heterologous expression of the saz gene(s) in Streptomyces albus J1074 yielded new prenylated indole alkaloids, showcasing the specificity and flexibility of the enzymes involved in the biosynthesis.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ramesh S. Gani, Avinash K. Kudva, Karabasanagouda Timanagouda, Raghuveer, Salma Begum Hussain Mujawar, Shrinivas D. Joshi, Shamprasad Varija Raghu
Summary: The study synthesized a series of novel oxadiazole-2-thiol derivatives and demonstrated their inhibitory activity against alpha-amylase and alpha-glucosidase in vitro. In vivo experiments on Drosophila melanogaster showed compounds 2b and 2g had better activity, indicating their potential as candidates for further development as novel antidiabetic agents.
BIOORGANIC CHEMISTRY
(2021)
Article
Environmental Sciences
Thomas M. Grant, David Rennison, Gunnar Cervin, Henrik Pavia, Claire Hellio, Valentin Foulon, Margaret A. Brimble, Patrick Cahill, Johan Svenson
Summary: Marine biofouling poses significant economic and environmental challenges to maritime industries, prompting the search for eco-friendly alternatives. Recent studies have shown that amphiphilic micropeptides exhibit excellent antifouling activity and biodegradability.
SCIENCE OF THE TOTAL ENVIRONMENT
(2022)
Article
Biochemistry & Molecular Biology
Haibo Wang, Senling Tang, Guoqing Zhang, Yang Pan, Wei Jiao, Huawu Shao
Summary: A series of N-substituted iminosugar C-glycosides were synthesized and tested for their inhibition on alpha-glucosidase. Compound 6e showed promise as a potent inhibitor of alpha-glucosidase and may be classified as an uncompetitive inhibitor based on enzymatic kinetic assays. The study of structure-activity relationships of these iminosugars serves as a starting point for the discovery of new alpha-glucosidase inhibitors.
Article
Chemistry, Applied
Chih-Yu Wu, Sivan Perumal Murugan, Yu-Wei Wang, Hao-Wei Pan, Bing-Jian Sun, Yu-Ting Lin, Siti Fatimah, Agnes H. H. Chang, Chinpiao Chen, Gene-Hsian Lee
Summary: This study developed an efficient method for preparing diastereo- and regio-selective indoline-fused 2,5-diketopiperazine scaffolds using Ugi reaction and a post-Ugi tandem reaction under basic conditions. The possible reaction mechanism and substrate structures were elucidated through single-crystal X-ray diffraction analysis and density functional theory calculations.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
