Recent advances in the biosynthesis of cytochalasans: a review

Abstract

Cytochalasans are a class of hybrid polyketide-peptide natural products with diverse activities, including anti-tumor, anti-fungal, anti-parasitic, and anti-HIV properties, demonstrating significant application potential and broad market prospects. With the development of microbial metabolic engineering and synthetic biology, microbial synthesis of cytochalasans has emerged as a cost-effective and efficient alternative to traditional extraction and chemical synthesis methods, facilitating green and sustainable production. To better understand and promote the efficient heterologous biosynthesis of cytochalasans, this review systematically summarizes and discusses the research progress on the biosynthesis of cytochalasans. Firstly, an overview of the classification, application and biological activity of cytochalasans is provided. Subsequently, we systematically review the relevant gene clusters, enzymes, and biosynthetic pathways involved in the biosynthesis of cytochalasans. Additionally, the latest progress in the design of microbial cell factories for producing cytochalasans and the strategies to enhance their performance are summarized and discussed. Finally, the current challenges in developing efficient cell factories for producing cytochalasans with renewable biomass as a substrate and the corresponding strategies are proposed, aiming to achieve higher-efficiency green biomanufacturing of cytochalasans.

Keywords

Cytochalasans / Gene clusters / Biosynthetic pathway / Aspochalasin D / Microbial synthesis / Biological Sciences / Biochemistry and Cell Biology / Microbiology / Chemical Sciences / Organic Chemistry

References

[1] SkellamE. The biosynthesis of cytochalasans. Nat Prod Rep, 2017, 34111252-63.

[2] ChenW, PangX, SongY, HuY, WangX, WangL, WangJ. Antitumor aspochalasin and antiviral benzofuran derivatives from a marine-derived fungus aspergillus sp. SCSIO41032. Nat Prod Res, 2024.

[3] Miao X-X, Hong L-L, Liu H-Y, Shang R-Y, Jiao W-H, Xu S-H, Lin H-W. Marcytoglobosins A and B, cytochalasans from a marine sponge associated Chaetomium globosum 162105 fungus. Chem Biodivers. 2024;21(7). https://doi.org/10.1002/cbdv.202400832.

[4] MiaoX, HongL, JuZ, LiuH, ShangR, LiP, LiuK, ChengB, JiaoW, XuS, LinH. Marchaetoglobins A–D: four cytochalasans with proangiogenic activity from the marine-sponge-associated fungus Chaetomium globosum 162105. ACS Omega, 2024, 92022450-8.

[5] XiaoL, LiuH, WuN, LiuM, WeiJ, ZhangY, LinX. Characterization of the high cytochalasin E and rosellichalasin producing-aspergillus sp nov. F1 isolated from marine solar saltern in China. World J Microbiol Biotechnol, 2013, 29111-7.

[6] AnL, LiC-P, ZhangH, WangM-L, KongL-Y, YangM-H. Four cytochalasin alkaloids produced by Chaetomium Globosum. Tetrahedron Lett, 2020, 6119151838.

[7] Huang G, Lin W, Li H, Tang Q, Hu Z, Huang H, Deng X, Xu Q. Pentacyclic cytochalasins and their derivatives from the endophytic fungus phomopsis sp. xz-18. Molecules. 2021;26(21). https://doi.org/10.3390/molecules26216505.

[8] ZhangJ-M, LiuX, WeiQ, MaC, LiD, ZouY. Berberine bridge enzyme-like oxidase-catalysed double bond isomerization acts as the pathway switch in cytochalasin synthesis. Nat Commun, 2022, 131225.

[9] HuangX, ZhouD, LiangY, LiuX, CaoF, QinY, MoT, XuZ, LiJ, YangR. Cytochalasins from endophytic Diaporthe sp GDG-118. Nat Prod Res, 2021, 35203396-403.

[10] YangZ, LiuH, SuZ, XuH, YuanZ, RaoY. Enhanced production of aspochalasin D through genetic engineering of aspergillus flavipes. Appl Microbiol Biotechnol, 2023, 10792911-20.

[11] LambertC, ShaoLL, ZengHX, SurupF, SaetangP, AimeMC, HusbandsDR, RottnerK, StradalTEB, StadlerM. Cytochalasans produced by Xylaria karyophthora and their biological activities. Mycologia, 2023, 1153277-87.

[12] ZhuH, ChenC, TongQ, ZhouY, YeY, GuL, ZhangY. Progress in the chemistry of cytochalasans. Prog Chem Org Nat Prod, 2021, 114: 1-134.

[13] ZhaoY, LongX, WuH, DengJ. Recent advances in the total synthesis of cytochalasan natural products using bioinspired strategies. Org Chem Front, 2022, 9246979-98.

[14] HeardSC, WuG, WinterJM. Discovery and characterization of a cytochalasan biosynthetic cluster from the marine-derived fungus aspergillus flavipes CNL-338. J Antibiot, 2020, 7311803-7.

[15] QiaoK, ChooiYH, TangY. Identification and engineering of the cytochalasin gene cluster from Aspergillus Clavatus NRRL 1. Metab Eng, 2011, 136723-32.

[16] HuY, DietrichD, XuW, PatelA, ThussJAJ, WangJ, YinW-B, QiaoK, HoukKN, VederasJC, TangY. A carbonate-forming Baeyer-Villiger monooxygenase. Nat Chem Biol, 2014, 107552-4.

[17] Li H, Wei H, Hu J, Lacey E, Sobolev AN, Stubbs KA, Solomon PS, Chooi Y-H. Genomics-driven discovery of phytotoxic cytochalasans involved in the virulence of the wheat pathogen parastagonospora nodorum. ACS Chem Biol. 2020;15(1):226–33 https://doi.org/10.1021/acschembio.9b00791

[18] IshiuchiK, NakazawaT, YagishitaF, MinoT, NoguchiH, HottaK, WatanabeK. Combinatorial generation of complexity by redox enzymes in the chaetoglobosin a biosynthesis. J Am Chem Soc, 2013, 135197371-7.

[19] Nielsen ML, Isbrandt T, Petersen LM, Mortensen UH, Andersen MR, Hoof JB, Larsen TO. Linker flexibility facilitates module exchange in fungal hybrid PKS-NRPS engineering. Plos One. 2016;11(8), https://doi.org/10.1371/journal.pone.0161199

[20] LiuJ, WangX, DaiG, ZhangY, BianX. Microbial chassis engineering drives heterologous production of complex secondary metabolites. Biotechnol Adv, 2022, 59: 107966.

[21] LuoZ, YanY, DuS, ZhuY, PanF, WangR, XuZ, XuX, LiS, XuH. Recent advances and prospects of Bacillus amyloliquefaciens as microbial cell factories: from rational design to industrial applications. Crit Rev Biotechnol, 2023, 4371073-91.

[22] Guan A, He Z, Wang X, Jia Z-J, Qin J. Engineering the next-generation synthetic cell factory driven by protein engineering. Biotechnol Adv. 2024;73. https://doi.org/10.1016/j.biotechadv.2024.108366.

[23] Lu M, Sha Y, Kumar V, Xu Z, Zhai R, Jin M. Transcription factor-based biosensor: a molecular-guided approach for advanced biofuel synthesis. Biotechnol Adv. 2024;72:108339–108339 https://doi.org/10.1016/j.biotechadv.2024.108339

[24] LuoZ, PanF, ZhuY, DuS, YanY, WangR, LiS, XuH. Synergistic improvement of 5-aminolevulinic acid production with synthetic scaffolds and system pathway engineering. ACS Synth Biol, 2022.

[25] JiangC, SongJ, ZhangJ, YangQ. New production process of the antifungal chaetoglobosin A using cornstalks. Braz J Microbiol, 2017, 483410-8.

[26] WangZ, CuiJ, GaoW, YangQ, ChenL, YangL, SunQ, ZhangH. Effects of rice straw structure on chaetoglobosin A production by Chaetomium globosum CGMCC 6882. Int J Biol Macromol, 2020, 150: 1223-8.

[27] WangW, GongJ, LiuX, DaiC, WangY, LiX-N, WangJ, LuoZ, ZhouY, XueY, ZhuH, ChenC, ZhangY. Cytochalasans produced by the coculture of aspergillus flavipes and Chaetomium Globosum. J Nat Prod, 2018, 8171578-87.

[28] RothweilerW, TammC. Isolation and structure of Phomin. Experientia, 1966, 2211750-2.

[29] ZhengCJ, ShaoCL, WuLY, ChenM, WangKL, ZhaoDL, SunXP, ChenGY, WangCY. Bioactive phenylalanine derivatives and cytochalasins from the soft coral-derived fungus, Aspergillus Elegans. Mar Drugs, 2013, 1162054-68.

[30] Kim EL, Wang H, Park JH, Hong J, Choi JS, Im DS, Chung HY, Jung JH. Cytochalasin derivatives from a jellyfish-derived fungus Phoma sp. Bioorg Med Chem Lett. 2015;25(10):2096–9. https://doi.org/10.1016/j.bmcl.2015.03.080

[31] Gu G, Hou XW, Xue MY, Jia XW, Pan XQ, Xu D, Dai JG, Lai DW, Zhou LG. Rosellichalasins A-H, cytotoxic cytochalasans from the endophytic fungus Rosellinia sp. Glinf021. Phytochemistry. 2024;222. https://doi.org/10.1016/j.phytochem.2024.114103.

[32] YangM-Y, WangY-X, ChangQ-H, LiL-F, LiuY-F, CaoF. Cytochalasans and azaphilones: suitable chemotaxonomic markers for the Chaetomium species. Appl Microbiol Biot, 2021, 10521–228139-55.

[33] WeiG, ChenC, TongQ, HuangJ, WangW, WuZ, YangJ, LiuJ, XueY, LuoZ, WangJ, ZhuH, ZhangY. Aspergilasines A-D: four merocytochalasans with new carbon skeletons from aspergillus flavipes QCS12. Org Lett, 2017, 19164399-402.

[34] Long X, Wu H, Ding Y, Qu C, Deng J. Biosynthetically inspired divergent syntheses of merocytochalasans. Chem. 2021;7(1):212–23. https://doi.org/10.1016/j.chempr.2020.11.010

[35] HoltzelA, SchmidDG, NicholsonGJ, KrastelP, ZeeckA, GebhardtK, FiedlerHP, JungG. Aspochalamins A-D and aspochalasin Z produced by the endosymbiotic Fungus Aspergillus Niveus LU 9575. II. Structure elucidation. J Antibiot (Tokyo), 2004, 5711715-20.

[36] GebhardtK, SchimanaJ, HöltzelA, DettnerK, DraegerS, BeilW, RheinheimerJ, FiedlerHP. Aspochalamins A-D and aspochalasin Z produced by the endosymbiotic Fungus Aspergillus Niveus LU 9575. I. Taxonomy, fermentation, isolation and biological activities. J Antibiot (Tokyo), 2004, 5711707-14.

[37] Aldridge DC, Armstrong JJ, Speake RN, Turner WB. The structures of cytochalasins A and B. J Chem Soc C. 1967;(0):1667–76. https://doi.org/10.1039/J39670001667

[38] Shu Y, Wang J-P, Li B-X, Gan J-L, Ding H, Liu R, Cai L, Ding Z-T. Bioactive cytochalasans from the fungus Arthrinium arundinis DJ-13. Phytochemistry. 2022;194:113009. https://doi.org/10.1016/j.phytochem.2021.113009

[39] SpudichJA, LinS, CytochalasinB. Its interaction with actin and actomyosin from muscle (cell movement-microfilaments-rabbit striated muscle). Proc Natl Acad Sci USA, 1972, 692442-6.

[40] BrownSS, SpudichJA. Mechanism of action of cytochalasin: evidence that it binds to actin filament ends. J Cell Biol, 1981, 883487-91.

[41] CooperJA. Effects of cytochalasin and phalloidin on actin. J Cell Biol, 1987, 10541473-8.

[42] Kretz R, Wendt L, Wongkanoun S, Luangsa-Ard JJ, Surup F, Helaly SE, Noumeur SR, Stadler M, Stradal TEB. The effect of cytochalasans on the actin cytoskeleton of eukaryotic cells and preliminary structure⁻activity relationships. Biomolecules. 2019;9(2). https://doi.org/10.3390/biom9020073

[43] Lambert C, Schmidt K, Karger M, Stadler M, Stradal TEB, Rottner K. Cytochalasans and their impact on actin filament remodeling. Biomolecules. 2023;13(8):1247. https://doi.org/10.3390/biom13081247

[44] Sekita S, Yoshihira K, Natori S, Udagawa S, Sakabe F, Kurata H, Umeda M. Chaetoglobosins, cytotoxic 10-(indol-3-yl)-[13]cytochalasans from Chaetomium Spp. I. production, isolation and some cytological effects of chaetoglobosins A-J. Chem Pharm Bull. 1982;30(5):1609–17 https://doi.org/10.1248/cpb.30.1609

[45] ZhangD, GeH, XieD, ChenR, ZouJH, TaoX, DaiJ. Periconiasins A-C, new cytotoxic cytochalasans with an unprecedented 9/6/5 tricyclic ring system from endophytic fungus Periconia Sp. Org Lett, 2013, 1571674-7.

[46] Lin Z, Zhu T, Wei H, Zhang G, Wang H, Gu Q. Spicochalasin A and new aspochalasins from the marine-derived fungus Spicaria elegans. Eur J Org Chem. 2009;2009(18):3045–51. https://doi.org/10.1002/ejoc.200801085

[47] ShojiK, OhashiK, SampeiK, OikawaM, MizunoK. Cytochalasin D acts as an inhibitor of the actin-cofilin interaction. Biochem Bioph Res Co, 2012, 424152-7.

[48] Ding G, Chen L, Chen A, Tian X, Chen X, Zhang H, Chen H, Liu XZ, Zhang Y, Zou ZM. Trichalasins C and D from the plant endophytic fungus Trichoderma gamsii. Fitoterapia. 2012;83(3):541-4. https://doi.org/10.1016/j.fitote.2011.12.021

[49] Xu D, Luo M, Liu F, Wang D, Pang X, Zhao T, Xu L, Wu X, Xia M, Yang X. Cytochalasan and tyrosine-derived alkaloids from the marine sediment-derived fungus Westerdykella dispersa and their bioactivities. Sci Rep. 2017;7(1):11956. https://doi.org/10.1038/s41598-017-12327-1

[50] GaoW, HeY, LiF, ChaiC, ZhangJ, GuoJ, ChenC, WangJ, ZhuH, HuZ, ZhangY. Antibacterial activity against drug-resistant microbial pathogens of cytochalasan alkaloids from the arthropod-associated fungus Chaetomium globosum TW1-1. Bioorg Chem, 2019, 83: 98-104.

[51] Zhao SS, Zhang YY, Yan W, Cao LL, Xiao Y, Ye YH. Chaetomium globosum CDW7, a potential biological control strain and its antifungal metabolites. FEMS Microbiol Lett. 2017;364(3). https://doi.org/10.1093/femsle/fnw287

[52] WuZ, ZhangX, AnbariWHA, ZhouQ, ZhouP, ZhangM, ZengF, ChenC, TongQ, WangJ, ZhuH, ZhangY. Cysteine residue containing merocytochalasans and 17,18-seco-aspochalasins from aspergillus micronesiensis. J Nat Prod, 2019, 8292653-8.

[53] Jouda JB, Tamokou JD, Mbazoa CD, Douala-Meli C, Sarkar P, Bag PK, Wandji J. Antibacterial and cytotoxic cytochalasins from the endophytic fungus Phomopsis sp. harbored in Garcinia kola (Heckel) nut. BMC Complem Altern Med. 2016;16(1):462. https://doi.org/10.1186/s12906-016-1454-9

[54] Zhang H, Zhang J, Bao R, Tian C, Tang Y. Collective total syntheses of cytochalasans and merocytochalasans. Tetrahedron Chem. 2022;2:100022. https://doi.org/10.1016/j.tchem.2022.100022

[55] Wei G, Tan D, Chen C, Tong Q, Li X-N, Huang J, Liu J, Xue Y, Wang J, Luo Z, Zhu H, Zhang Y. Flavichalasines A–M, cytochalasan alkaloids from Aspergillus flavipes. Sci Rep. 2017;7(1):42434. https://doi.org/10.1038/srep42434

[56] JayasuriyaH, HerathKB, OndeykaJG, PolishookJD, BillsGF, DombrowskiAW, SpringerMS, SicilianoS, MalkowitzL, SanchezM, GuanZ, TiwariS, StevensonDW, BorrisRP, SinghSB. Isolation and structure of antagonists of chemokine receptor (CCR5). J Nat Prod, 2004, 6761036-8.

[57] RochfortS, FordJ, OvendenS, WanSS, GeorgeS, WildmanH, TaitRM, Meurer-GrimesB, CoxS, CoatesJ, RhodesD. A novel aspochalasin with HIV-1 integrase inhibitory activity from Aspergillus flavipes. J Antibiot (Tokyo), 2005, 584279-83.

[58] Chen C, Zhu H, Wang J, Yang J, Li X-N, Wang J, Chen K, Wang Y, Luo Z, Yao G, Xue Y, Zhang Y. Armochaetoglobins k–r, anti-hiv pyrrole-based cytochalasans from Chaetomium globosum Tw1-1. Eur J Org Chem. 2015;2015(14):3086–94. https://doi.org/10.1002/ejoc.201403678

[59] MakiokaA, KumagaiM, KobayashiS, TakeuchiT. Different effects of cytochalasins on the growth and differentiation of Entamoeba invadens. Parasitol Res, 2004, 93168-71.

[60] Dou H, Song Y, Liu X, Gong W, Li E, Tan R, Hou Y. Chaetoglobosin Fex from the marine-derived endophytic fungus inhibits induction of inflammatory mediators via toll-like receptor 4 signaling in macrophages. Biol Pharm Bull. 2011;34(12):1864–73. https://doi.org/10.1248/bpb.34.1864

[61] George TP, Cook HW, Byers DM, Palmer FB, Spence MW. Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis by cytochalasin B in cultured glioma cells: potential regulation of biosynthesis by Ca²⁺-dependent mechanisms. Biochim Biophys Acta. 1991;1084(2):185–93. https://doi.org/10.1016/0005-2760(91)90219-8

[62] Luo H, Li B, Li Z, Cutler SJ, Rankin GO, Chen YC. Chaetoglobosin K inhibits tumor angiogenesis through downregulation of vascular epithelial growth factor-binding hypoxia-inducible factor 1α. Anticancer Drugs. 2013;24(7):715–24. https://doi.org/10.1097/CAD.0b013e3283627a0b

[63] UdagawaT, YuanJ, PanigrahyD, ChangYH, ShahJ, D’AmatoRJ. Cytochalasin E, an epoxide containing aspergillus-derived fungal metabolite, inhibits angiogenesis and tumor growth. J Pharmacol Exp Ther, 2000, 2942421-7.

[64] WurdakH, ZhuS, MinKH, AimoneL, LairsonLL, WatsonJ, ChopiukG, DemasJ, CharetteB, HalderR, WeerapanaE, CravattBF, ClineHT, PetersEC, ZhangJ, WalkerJR, WuC, ChangJ, TuntlandT, ChoCY, SchultzPG. A small molecule accelerates neuronal differentiation in the adult rat. Proc Natl Acad Sci USA, 2010, 1073816542-7.

[65] Schümann J, Hertweck C. Molecular basis of cytochalasan biosynthesis in fungi: gene cluster analysis and evidence for the involvement of a PKS-NRPS hybrid synthase by RNA silencing. J Am Chem Soc. 2007;129(31):9564. https://doi.org/10.1021/ja072884t

[66] Sato M, Yagishita F, Mino T, Uchiyama N, Patel A, Chooi YH, Goda Y, Xu W, Noguchi H, Yamamoto T, Hotta K, Houk KN, Tang Y, Watanabe K. Involvement of lipocalin-like CghA in decalin-forming Stereoselective Intramolecular [4 + 2] Cycloaddition. Chembiochem. 2015;16(16):2294–8. https://doi.org/10.1002/cbic.201500386

[67] CollemareJ, PianfettiM, HoulleA-E, MorinD, CambordeL, GageyM-J, BarbisanC, FudalI, LebrunM-H, BöhnertHU. Magnaporthe Grisea avirulence gene ACE1 belongs to an infection-specific gene cluster involved in secondary metabolism. New Phytol, 2008, 1791196-208.

[68] Song Z, Bakeer W, Marshall JW, Yakasai AA, Khalid RM, Collemare J, Skellam E, Tharreau D, Lebrun MH, Lazarus CM, Bailey AM, Simpson TJ, Cox RJ. Heterologous expression of the avirulence gene ACE1 from the fungal rice pathogen Magnaporthe oryzae. Chem Sci. 2015;6(8):4837–45. https://doi.org/10.1039/c4sc03707c

[69] WangC, HantkeV, CoxRJ, SkellamE. Targeted gene inactivations expose silent cytochalasans in Magnaporthe Grisea NI980. Org Lett, 2019, 21114163-7.

[70] Hantke V, Skellam EJ, Cox RJ. Evidence for enzyme catalysed intramolecular 4 + 2 diels-alder cyclization during the biosynthesis of pyrichalasin H. Chem Commun. 2020;56(19):2925–8. https://doi.org/10.1039/c9cc09590j

[71] Chen M, Jiang Y, Ding Y. Recent progress in unraveling the biosynthesis of natural sunscreens mycosporine-like amino acids. J Ind Microbiol Biotechnol. 2023;50(1). https://doi.org/10.1093/jimb/kuad038

[72] CravensA, PayneJ, SmolkeCD. Synthetic biology strategies for microbial biosynthesis of plant natural products. Nat Commun, 2019, 1012142.

[73] Zhu X, Liu X, Liu T, Wang Y, Ahmed N, Li Z, Jiang H. Synthetic biology of plant natural products: from pathway elucidation to engineered biosynthesis in plant cells. Plant Commun. 2021;2(5):100229. https://doi.org/10.1016/j.xplc.2021.100229

[74] ScherlachK, BoettgerD, RemmeN, HertweckC. The chemistry and biology of cytochalasans. Nat Prod Rep, 2010, 276869-86.

[75] FujiiR, MinamiA, GomiK, OikawaH. Biosynthetic assembly of cytochalasin backbone. Tetrahedron Lett, 2013, 54232999-3002.

[76] NiehausEM, KleigreweK, WiemannP, StudtL, SieberCM, ConnollyLR, FreitagM, GüldenerU, TudzynskiB, HumpfHU. Genetic manipulation of the Fusarium fujikuroi fusarin gene cluster yields insight into the complex regulation and fusarin biosynthetic pathway. Chem Biol, 2013, 2081055-66.

[77] Li L, Yu P, Tang MC, Zou Y, Gao SS, Hung YS, Zhao M, Watanabe K, Houk KN, Tang Y. Biochemical characterization of a eukaryotic decalin-forming diels-alderase. J Am Chem Soc. 2016;138(49):15837–40. https://doi.org/10.1021/jacs.6b10452

[78] Zhang H, Hantke V, Bruhnke P, Skellam EJ, Cox RJ. Chemical and genetic studies on the formation of pyrrolones during the biosynthesis of cytochalasans. Chemistry. 2021;27(9):3106–13. https://doi.org/10.1002/chem.202004444

[79] Reyes JR, Winter N, Spessert L, Trauner D. Biomimetic synthesis of (+)-Aspergillin PZ. Angew Chem Int Edit. 2018;57(47):15587–91. https://doi.org/10.1002/anie.201809703

[80] YuL, DingW, MaZ. Induced production of cytochalasans in co-culture of marine fungus aspergillus flavipes and actinomycete Streptomyces Sp. Nat Prod Res, 2016, 30151718-23.

[81] Hantke V, Wang C, Skellam EJ, Cox RJ. Function of pathway specific regulators in the ACE1 and pyrichalasin H biosynthetic gene clusters. RSC Adv. 2019;9(61):35797–802. https://doi.org/10.1039/c9ra07028a

[82] ChengM, ZhaoS, LiuH, LiuY, LinC, SongJ, ThawaiC, CharoensettasilpS, YangQ. Functional analysis of a chaetoglobosin a biosynthetic regulator in Chaetomium globosum. Fungal Biol, 2021, 1253201-10.

[83] Xiang B, Hao X, Xie Q, Shen G, Liu Y, Zhu X. Deletion of a rare fungal pks cgpks11 promotes chaetoglobosin a biosynthesis, yet defers the growth and development of Chaetomium globosum. J Fungi (Basel). 2021;7(9). https://doi.org/10.3390/jof7090750.

[84] Zhao S, Lin C, Cheng M, Zhang K, Wang Z, Zhao T, Yang Q. New insight into the production improvement and resource generation of chaetoglobosin A in Chaetomium globosum. Microb Biotechnol. 2022;15(10):2562–77. https://doi.org/10.1111/1751-7915.14111

[85] XuZ-L, LiB-C, HuangL-L, LvL-X, LuoY, XuW-F, YangR-Y. Two new cytochalasins from the endophytic fungus Xylaria sp. GDGJ-77B. Nat Prod Res, 2024, 3891503-9.

[86] GuoQ, ShenS, WangX, ShiL, RenY, LiD, YinZ, ZhangJ, YangB, WangX, DingG, ChenL. Bioactive cytochalasans from the desert soil-derived fungus chaetomium madrasense 375 obtained via a chemical engineering strategy. Front Microbiol, 2023, 14: 1292870.

[87] Gao W, Jiang R, Zeng H, Cao J, Hu Z, Zhang Y, Armochaetoglasins L. and M, new cytochalasans from an arthropod-derived fungus Chaetomium globosum. Nat Prod Res. 2024;38(9):1599–605. https://doi.org/10.1080/14786419.2022.2150846

[88] Chiang CY, Ohashi M, Tang Y. Deciphering chemical logic of fungal natural product biosynthesis through heterologous expression and genome mining. Nat Prod Rep. 2023;40(1):89–127. https://doi.org/10.1039/d2np00050d

[89] Guo H, Diao QP, Zhang B, Wang KH. Perenniporins A-C, new cytochalasans from the fungus Perenniporia subacida with cytotoxic and anti-inflammatory activities. Phytochem Lett. 2021;46:162–5. https://doi.org/10.1016/j.phytol.2021.10.004

[90] Li TT, Wang Y, Li L, Tang MY, Meng QH, Zhang C, Hua EB, Pei YH, Sun Y. New cytotoxic cytochalasans from a plant-associated fungus Chaetomium globosum kz-19. Mar Drugs. 2021;19(8). https://doi.org/10.3390/md19080438

[91] Demain AL, Hunt NA, Malik V, Kobbe B, Hawkins H, Matsuo K, Wogan GN. Improved procedure for production of cytochalasin E and tremorgenic mycotoxins by Aspergillus clavatus. Appl Environ Microb. 1976;31(1):138–40. https://doi.org/10.1128/aem.31.1.138-140.1976

[92] Zhan C, Shen S, Yang C, Liu Z, Fernie AR, Graham IA, Luo J. Plant metabolic gene clusters in the multi-omics era. Trends Plant Sci. 2022;27(10):981–1001. https://doi.org/10.1016/j.tplants.2022.03.002

[93] Rai A, Hirakawa H, Nakabayashi R, Kikuchi S, Hayashi K, Rai M, Tsugawa H, Nakaya T, Mori T, Nagasaki H, Fukushi R, Kusuya Y, Takahashi H, Uchiyama H, Toyoda A, Hikosaka S, Goto E, Saito K, Yamazaki M. Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis. Nat Commun. 2021;12(1):405. https://doi.org/10.1038/s41467-020-20508-2

[94] Pereira R, Wei Y, Mohamed E, Radi M, Malina C, Herrgård MJ, Feist AM, Nielsen J, Chen Y. Adaptive laboratory evolution of tolerance to dicarboxylic acids in Saccharomyces cerevisiae. Metab Eng. 2019;56:130–41. https://doi.org/10.1016/j.ymben.2019.09.008

[95] Wang Z, Zhou L, Lu M, Zhang Y, Perveen S, Zhou H, Wen Z, Xu Z, Jin M. Adaptive laboratory evolution of Yarrowia Lipolytica improves ferulic acid tolerance. Appl Microbiol Biotechnol. 2021;105(4):1745–58. https://doi.org/10.1007/s00253-021-11130-3

[96] Jiang B, Liu J, Wang J, Zhao G, Zhao Z. Adaptive evolution for the efficient production of high-quality d-lactic acid using engineered Klebsiella pneumoniae. Microorganisms. 2024;12(6):1167.

[97] Gao Y, Li F, Luo Z, Deng Z, Zhang Y, Yuan Z, Liu C, Rao Y. Modular assembly of an artificially concise biocatalytic cascade for the manufacture of phenethylisoquinoline alkaloids. Nat Commun. 2024;15(1):30–30. https://doi.org/10.1038/s41467-023-44420-7

[98] LuoZ, LiuN, LazarZ, ChatzivasileiouA, WardV, ChenJ, ZhouJ, StephanopoulosG. Enhancing isoprenoid synthesis in Yarrowia Lipolytica by expressing the isopentenol utilization pathway and modulating intracellular hydrophobicity. Metab Eng, 2020, 61: 344-51.

[99] Chatzivasileiou AO, Ward V, Edgar SM, Stephanopoulos G. Two-step pathway for isoprenoid synthesis. Proc Natl Acad Sci USA. 2019;116(2):506–11. https://doi.org/10.1073/pnas.1812935116

[100] Zhao M, Qin Z, Abdullah A, Xiao Y. Construction of biocatalytic cascades for the synthesis of benzylisoquinoline alkaloids from p-coumaric acid derivatives and dopamine. Green Chem. 2022;24(8):3225–34. https://doi.org/10.1039/D1GC04759K

Funding

National Key Research and Development Program of China(2021YFC2102700)

the Basic Research Program of Jiangsu and supported by the Jiangsu Basic Research Center for Synthetic Biology(BK20233003)

National Natural Science Foundation of China(22108122)

the Fundamental Research Funds for the Central Universities(JUSRP124020)

RIGHTS & PERMISSIONS

Jiangnan University