Discovery of Leinamycin Family of Natural Products by Genome Mining Highlighting Nature's Combinatorial Biosynthesis Repertoire (PNAS, 2017)

 

 

Discovery and Characterization of the First ACC synthase of Bacterial Origin

(JACS, 2018)

 

* Corresponding authors  # Co-first authors 

30.Steele AD#, Jiang H#, Pan G, Lim SK, Kalkreuter E, Kwong T, Ju J, Rajski S, Shen B*. Discrete Acyltransferases and Thioesterases in Iso-Migrastatin and Lactimidomycin Biosynthesis. Biochemistry. 2024, 63, 4, 563–75.

29.Gao J#, Li L#, Shen S, Ai G, Wang B, Guo F, Yang T, Han H, Xu Z,Pan G*, Fan K*. Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis. Beilstein J. Org. Chem. 2024, 20, 1198–1206.

28.Kong Y, Liu Y, Wang K, Wang T, Wang C, Ai B, Jia H,Pan G, Yin M, Xu Z*. Confirmation of the stereochemistry of spiroviolene. Beilstein J. Org. Chem. 2024, 20, 852–858.

27. Zhang C, Zhao Y, Li Z, Wang W, Huang Y,Pan G, Fan K*. Molecular mechanism of GylR-mediated regulation of glycerol metabolism in Streptomyces clavuligerus NRRL 3585. Front Microbiol. 2022, 13, 1078293.

26. Wang H#, Wang L#, Fan K,Pan G*. Tetracycline family natural products: discovery, biosynthesis and engineering. Chin J Nat Medicines. 2022, 20(10):773-794.

25. Zhang Z, Li P*, Wang M, Zhang Y, Wu B, Tao Y, Pan G*, Chen Y*. (S)-3-aminopiperidine-2,6-dione is a biosynthetic intermediate of microbial blue pigment indigoidine.mLife. 2022, 1(2):146–155

24. Wang J#, Li Z#, Wang W, Pang S, Yao Y, Yuan F, Wang H, Xu Z, Pan G, Liu Z, Chen Y*, Fan K*. Dynamic Control Strategy to Produce Riboflavin with Lignocellulose Hydrolysate in the Thermophile Geobacillus thermoglucosidasius. ACS Synth Biol. 2022, 11(6):2163-2174.

23. Meng S#, Steele AD#, Yan W, Pan G, Kalkreuter E, Liu YC, Xu Z, Shen B. Thiocysteine lyases as polyketide synthase domains installing hydropersulfide into natural products and a hydropersulfide methyltransferase. Nat Commun. 2021, 12(1):5672. 

22. Wang L, Fan K, Wang H, Hu H, Xiang L, Ai G, Pan G*. Bioinformatics-directed discovery of dehydrated linear trimer and dimer of 2,3-dihydroxybenzoyl-L-serine from Streptomyces albofaciens JCM 4342. Microbiology China. 2021,  48(7): 2307-2317.

21. Yuan F, Yin S, Xu Y, Xiang L, Wang H, Li Z, Fan K*, Pan G*. The richness and diversity of catalases in bacteria. Front. Microbiol. 2021, doi: 10.3389/fmicb.2021.645477. 

20. Zhang Q#, Ren JW#, Wang W, Zhai J, Yang J, Liu N, Huang Y, Chen Y, Pan G*, Fan K*. A versatile transcription-translation in one approach for activation of cryptic biosynthetic gene clusters. ACS Chem Biol. 2020, 15(9), 2551-2557. 

19. Kalkreuter E, Pan G, Cepeda AJ, Shen B*. Targeting bacterial genomes for natural product discovery. Trends Pharmacol Sci. 2020, 41(1):13-26. 

18. Steele AD, Kalkreuter E, Pan G, Meng S, Shen B*. Hybrid Peptide-Polyketide Natural Product Biosynthesis. In: Hung-Wen (Ben) Liu, Tadhg P. Begley (eds.) Comprehensive Natural Products III: Chemistry and Biology. vol. 2, 2020, pp. 284-335. Elsevier. 

17. McAlpine et al. The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research. Nat Prod Rep. 2019, 36(1):35-107. 

16. Xu Z#, Pan G#, Zhou H, Shen B*. Discovery and characterization of 1-aminocyclopropane-1-carboxylic acid synthase of bacterial origin. J Am Chem Soc. 2018, 140(49):16957-16961. (Hot off the press) 

15. Kwong T#, Ma M#, Pan G, Hindra, Yang D, Yang C, Lohman JR, Rudolf JD, Cleveland JL, Shen B*. P450-catalyzed tailoring steps in leinamycin biosynthesis featuring regio- and stereoselective hydroxylations and substrate promiscuities. Biochemistry. 2018, 57(33):5005–5013. 

14. Pan G#, Xu Z#, Guo Z, Hindra, Ma M, Yang D, Zhou H, Gansemans Y, Zhu X, Huang Y, Zhao LX, Jiang Y, Cheng J, Van Nieuwerburgh F, Suh JW, Duan Y, Shen B*. Discovery of the leinamycin family of natural products by mining actinobacterial genomes. Proc Natl Acad Sci U S A. 2017, 114(52):E11131-E11140. (Highlighted by F1000) 

13. Zhang B#, Xu Z#, Teng Q#, Pan G, Ma M, Shen B*. A Long-range effecting dehydratase domain as the missing link for C17-dehydration in iso-migrastatin biosynthesis. Angew. Chem. Int. Ed. 2017, 56(25):7247-7251. 

12. Li L#, Pan G#, Zhu X, Fan K, Gao W, Ai G, Ren J, Shi M, Olano C, Salas J, Yang K*. Engineered jadomycin analogues with altered sugar moieties revealing JadS as a substrate flexible O-glycosyltransferase. Appl Microbiol Biotechnol. 2017, 101(13):5291-5300. 

11. Pan G#, Gao X#, Fan K#, Liu J, Meng B, Gao J, Wang B, Zhang C, Han H, Ai G, Chen Y, Wu D*, Liu ZJ*, Yang K*. Structure and function of a C-C bond cleaving oxygenase in atypical angucycline biosynthesis. ACS Chem Biol. 2017, 12(1):142-152. 

10. Guo Z, Pan G, Xu Z, Yang D, Hindra, Zhu X, Huang Y, Zhao LX, Jiang Y, Duan Y, Shen B*. New isofuranonaphthoquinones and isoindolequinones from Streptomyces sp. CB01883. J Antibiot. 2017, 70(4):414-422. 

9. Huang Y#, Yang D#, Pan G, Tang GL, Shen B*. Characterization of LnmO as a pathway-specific Crp/Fnr-type positive regulator for leinamycin biosynthesis in Streptomyces atroolivaceus and its application for titer improvement. Appl Microbiol Biotechnol. 2016, 100(24):10555-10562. 

8. Huang Y, Tang GL, Pan G, Chang CY, Shen B. Characterization of the Ketosynthase and Acyl Carrier Protein Domains at the LnmI Nonribosomal Peptide Synthetase-Polyketide Synthase Interface for Leinamycin Biosynthesis. Org Lett. 2016, 18(17):4288-4291.  

7. Zhang B#, Yang D#, Yan Y, Pan G, Xiang W*, Shen B*. Overproduction of lactimidomycin by cross-overexpression of genes encoding Streptomyces antibiotic regulatory proteins. Appl Microbiol Biotechnol. 2016, 100(5):2267-2277. 

6. Medema MH et al. (2015) Minimum information about a biosynthetic gene cluster. Nat Chem Biol. 2015, 11(9):625-631. (Highlighted by F1000) 

5. Wang B#, Ren J#, Li L, Guo F, Pan G, Ai G, Aigle B, Fan K*, Yang K*. Kinamycin biosynthesis employs a conserved pair of oxidases for B-ring contraction. Chem Commun. 2015, 51(42):8845-8848. 

4. Liu Y, Ryu H, Ge B, Pan G, Sun L, Park K, Zhang K*. Improvement of wuyiencin biosynthesis in Streptomyces wuyiensis CK-15 by identification of a key regulator, WysR. J Microbiol Biotechnol. 2014, 24(12):1644-1653. 

3. Wang W#, Ji J#, Li X, Wang J, Li S, Pan G, Fan K, Yang K*. Angucyclines as signals modulate the behaviors of Streptomyces coelicolor. Proc Natl Acad Sci U S A. 2014, 111(15):5688-5693. 

2. Zhang Y#, Pan G#, Zou Z, Fan K, Yang K*, Tan H*. JadR*-mediated feed-forward regulation of cofactor supply in jadomycin biosynthesis. Mol Microbiol. 2013, 90(4):884-897. 

1. Fan K#, Pan G#, Peng X, Zheng J, Gao W, Wang J, Wang W, Li Y, Yang K*. Identification of JadG as the B ring opening oxygenase catalyzing the oxidative C-C bond cleavage reaction in jadomycin biosynthesis. Chem Biol. 2012, 19(11):1381-1390.  

1. 杨克迁, 范可强, 潘国辉, 彭晓静. JadG蛋白在催化角蒽环芳香聚酮氧化开环和氨基酸插入反应中的应用，中国，CN201210575469.9，2014-9-17