Jun ZHANG1, Shixue JIN2, Qian YUN2, Xudong QU1
Received:
2023-11-30
Revised:
2024-01-08
Published:
2024-01-23
Contact:
Xudong QU
张俊1, 金诗雪2, 云倩2, 瞿旭东1
通讯作者:
瞿旭东
作者简介:
基金资助:
CLC Number:
Jun ZHANG, Shixue JIN, Qian YUN, Xudong QU. Unnatural Extender Unit Biosynthesis and Application in Polyketides Structural Modification[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2023-093.
张俊, 金诗雪, 云倩, 瞿旭东. 聚酮化合物非天然延伸单元的生物合成与结构改造应用[J]. 合成生物学, DOI: 10.12211/2096-8280.2023-093.
Add to citation manager EndNote|Ris|BibTeX
URL: https://synbioj.cip.com.cn/EN/10.12211/2096-8280.2023-093
Fig. 1 Selected polyketide drugs(A) and Classical polyketide synthase assembly line for erythromycin A biosynthesis(B)(AT—Acyltransferase; ACP—Acyl carrier protein; DH—Dehydratase; ER—Enoylreductase; KR—Ketoreductase; KS—Ketosynthase)
Fig. 2 Two classes of natural extender units(A) and Biosynthesis of Malonyl-CoA extender units(B)(MCS—Malonyl-CoA synthetase; CCRC—Crotonyl-CoA reductase/carboxylase; ACC—Acyl-CoA carboxylase; MCE—Methyl Malonyl-CoA epimerase; CoA—Coenzyme A; ACP—Acyl carrier protein)
Fig. 3 Biosynthesis of unnatural extender units through substrates scope examining or enzymatic engineering(MCS—Malonyl-CoA synthetase; CCRC—Crotonyl-CoA reductase/carboxylase; ACC—Acyl-CoA carboxylase; CoA—Coenzyme A; SNAC—N-acetylcysteamine; Pant—pantetheine)
Fig. 4 Modification of polyketide sidechain through biosynthesis of unnatural extender units combining a natural promiscuous AT(Blue represents unnatural sidechains introduced by unnatural extender units)
1 | ROBERTSEN H L, MUSIOL-KROLL E M. Actinomycete-derived polyketides as a source of antibiotics and lead structures for the development of new antimicrobial drugs[J]. Antibiotics, 2019, 8(4): 157. |
2 | DAVISON E K, BRIMBLE M A. Natural product derived privileged scaffolds in drug discovery[J]. Current Opinion in Chemical Biology, 2019, 52: 1-8. |
3 | NEWMAN D J, CRAGG G M. Natural products as sources of new drugs over the nearly four decades from 01/1981 to 09/2019[J]. Journal of Natural Products, 2020, 83(3): 770-803. |
4 | LI G, LOU H X. Strategies to diversify natural products for drug discovery[J]. Medicinal Research Reviews, 2018, 38(4): 1255-1294. |
5 | KENNEDY J. Mutasynthesis, chemobiosynthesis, and back to semi-synthesis: combining synthetic chemistry and biosynthetic engineering for diversifying natural products[J]. Natural Product Reports, 2008, 25(1): 25-34. |
6 | LIN Z, QU X D. Emerging diversity in polyketide synthase[J]. Tetrahedron Letters, 2022, 110: 154183. |
7 | YAN X L, ZHANG J, TAN H Q, et al. A pair of atypical KAS III homologues with initiation and elongation functions program the polyketide biosynthesis in asukamycin[J]. Angewandte Chemie International Edition, 2022, 61(19): e202200879. |
8 | KEATINGE-CLAY A T. The structures of type I polyketide synthases[J]. Natural Product Reports, 2012, 29(10): 1050-1073. |
9 | ROBBINS T, LIU Y C, CANE D E, et al. Structure and mechanism of assembly line polyketide synthases[J]. Current Opinion in Structural Biology, 2016, 41: 10-18. |
10 | HERTWECK C. The biosynthetic logic of polyketide diversity[J]. Angewandte Chemie International Edition, 2009, 48(26): 4688-4716. |
11 | FISCHBACH M A, WALSH C T. Assembly-line enzymology for polyketide and nonribosomal Peptide antibiotics: logic, machinery, and mechanisms[J]. Chemical Reviews, 2006, 106(8): 3468-3496. |
12 | WALKER P D, WEIR A N M, WILLIS C L, et al. Polyketide β-branching: diversity, mechanism and selectivity[J]. Natural Product Reports, 2021, 38(4): 723-756. |
13 | CHAN Y A, PODEVELS A M, KEVANY B M, et al. Biosynthesis of polyketide synthase extender units[J]. Natural Product Reports, 2009, 26(1): 90-114. |
14 | LITTLE R F, HERTWECK C. Chain release mechanisms in polyketide and non-ribosomal peptide biosynthesis[J]. Natural Product Reports, 2022, 39(1): 163-205. |
15 | MOORE B S, HERTWECK C. Biosynthesis and attachment of novel bacterial polyketide synthase starter units[J]. Natural Product Reports, 2002, 19(1): 70-99. |
16 | WILSON M C, MOORE B S. Beyond ethylmalonyl-CoA: the functional role of crotonyl-CoA carboxylase/reductase homologs in expanding polyketide diversity[J]. Natural Product Reports, 2012, 29(1): 72-86. |
17 | RAY L, MOORE B S. Recent advances in the biosynthesis of unusual polyketide synthase substrates[J]. Natural Product Reports, 2016, 33(2): 150-161. |
18 | BISSELL A U, RAUTSCHEK J, HOEFGEN S, et al. Biosynthesis of the sphingolipid inhibitors sphingofungins in filamentous fungi requires aminomalonate as a metabolic precursor[J]. ACS Chemical Biology, 2022, 17(2): 386-394. |
19 | ZHAO C H, COUGHLIN J M, JU J H, et al. Oxazolomycin biosynthesis in Streptomyces albus JA3453 featuring an "acyltransferase-less" type I polyketide synthase that incorporates two distinct extender units[J]. Journal of Biological Chemistry, 2010, 285(26): 20097-20108. |
20 | CHEN D D, ZHANG Q, ZHANG Q L, et al. Improvement of FK506 production in Streptomyces tsukubaensis by genetic enhancement of the supply of unusual polyketide extender units via utilization of two distinct site-specific recombination systems[J]. Applied and Environmental Microbiology, 2012, 78(15): 5093-5103. |
21 | KATO Y, BAI L Q, XUE Q, et al. Functional expression of genes involved in the biosynthesis of the novel polyketide chain extension unit, methoxymalonyl-acyl carrier protein, and engineered biosynthesis of 2-desmethyl-2-methoxy-6-deoxyerythronolide B[J]. Journal of the American Chemical Society, 2002, 124(19): 5268-5269. |
22 | CARPENTER S M, WILLIAMS G J. Extender unit promiscuity and orthogonal protein interactions of an aminomalonyl-ACP utilizing trans-acyltransferase from zwittermicin biosynthesis[J]. ACS Chemical Biology, 2018, 13(12): 3361-3373. |
23 | DODGE G J, MALONEY F P, SMITH J L. Protein-protein interactions in "cis-AT" polyketide synthases[J]. Natural Product Reports, 2018, 35(10): 1082-1096. |
24 | KOSOL S, JENNER M, LEWANDOWSKI J R, et al. Protein-protein interactions in trans-AT polyketide synthases[J]. Natural Product Reports, 2018, 35(10): 1097-1109. |
25 | ZHANG F, JI H N, ALI I, et al. Structural and biochemical insight into the recruitment of acyl carrier protein-linked extender units in ansamitocin biosynthesis[J]. Chembiochem, 2020, 21(9): 1309-1314. |
26 | ZHENG M M, ZHANG J, ZHANG W, et al. An atypical acyl-CoA synthetase enables efficient biosynthesis of extender units for engineering a polyketide carbon scaffold[J]. Angewandte Chemie International Edition, 2022, 61(43): e202208734. |
27 | AN J H, KIM Y S. A gene cluster encoding malonyl-CoA decarboxylase (MatA), malonyl-CoA synthetase (MatB) and a putative dicarboxylate carrier protein (MatC) in Rhizobium trifolii: cloning, sequencing, and expression of the enzymes in Escherichia coli [J]. European Journal of Biochemistry, 1998, 257(2): 395-402. |
28 | POHL N L, HANS M, LEE H Y, et al. Remarkably broad substrate tolerance of malonyl-CoA synthetase, an enzyme capable of intracellular synthesis of polyketide precursors[J]. Journal of the American Chemical Society, 2001, 123(24): 5822-5823. |
29 | HUGHES A J, KEATINGE-CLAY A. Enzymatic extender unit generation for in vitro polyketide synthase reactions: structural and func-tional showcasing of Streptomyces coelicolor MatB[J]. Chemistry & Biology, 2011, 18(2): 165-176. |
30 | ERB T J, BERG I A, BRECHT V, et al. Synthesis of C5-dicarboxylic acids from C2-units involving crotonyl-CoA carboxylase/reductase: the ethylmalonyl-CoA pathway[J]. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104(25): 10631-10636. |
31 | YAN Y, CHEN J, ZHANG L H, et al. Multiplexing of combinatorial chemistry in antimycin biosynthesis: expansion of molecular diversity and utility[J]. Angewandte Chemie International Edition, 2013, 52(47): 12308-12312. |
32 | VÖGELI B, GEYER K, GERLINGER P D, et al. Combining promiscuous acyl-CoA oxidase and enoyl-CoA carboxylase/reductases for atypical polyketide extender unit biosynthesis[J]. Cell Chemical Biology, 2018, 25(7): 833-839.e4. |
33 | RAY L, VALENTIC T R, MIYAZAWA T, et al. A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units[J]. Nature Communications, 2016, 7: 13609. |
34 | ZHANG J, ZHENG M M, YAN J Y, et al. A permissive medium chain acyl-CoA carboxylase enables the efficient biosynthesis of extender units for engineering polyketide carbon scaffolds[J]. ACS Catalysis, 2021, 11(19): 12179-12185. |
35 | TRAN T H, HSIAO Y S, JO J, et al. Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase[J]. Nature, 2015, 518(7537): 120-124. |
36 | FARINAS E T, BULTER T, ARNOLD F H. Directed enzyme evolution[J]. Current Opinion in Biotechnology, 2001, 12(6): 545-551. |
37 | NODA-GARCIA L, TAWFIK D S. Enzyme evolution in natural products biosynthesis: target- or diversity-oriented?[J]. Current Opinion in Chemical Biology, 2020, 59: 147-154. |
38 | KORYAKINA I, WILLIAMS G J. Mutant malonyl-CoA synthetases with altered specificity for polyketide synthase extender unit generation[J]. Chembiochem, 2011, 12(15): 2289-2293. |
39 | KORYAKINA I, MCARTHUR J, RANDALL S, et al. Poly specific trans-acyltransferase machinery revealed via engineered acyl-CoA synthetases[J]. ACS Chemical Biology, 2013, 8(1): 200-208. |
40 | ZHANG L H, MORI T, ZHENG Q F, et al. Rational control of polyketide extender units by structure-based engineering of a crotonyl-CoA carboxylase/reductase in antimycin biosynthesis[J]. Angewandte Chemie International Edition, 2015, 54(45): 13462-13465. |
41 | QUADE N, HUO L J, RACHID S, et al. Unusual carbon fixation gives rise to diverse polyketide extender units[J]. Nature Chemical Biology, 2012, 8(1): 117-124. |
42 | TIAN W Y, CHEN X R, ZHANG J, et al. Biosynthesis of tetronates by a nonribosomal peptide synthetase-polyketide synthase system[J]. Organic Letters, 2023, 25(10): 1628-1632. |
43 | AWAKAWA T, FUJIOKA T, ZHANG L H, et al. Reprogramming of the antimycin NRPS-PKS assembly lines inspired by gene evolution[J]. Nature Communications, 2018, 9(1): 3534. |
44 | WALKER M C, THURONYI B W, CHARKOUDIAN L K, et al. Expanding the fluorine chemistry of living systems using engineered polyketide synthase pathways[J]. Science, 2013, 341(6150): 1089-1094. |
45 | SIRIRUNGRUANG S, AD O, PRIVALSKY T M, et al. Engineering site-selective incorporation of fluorine into polyketides[J]. Nature Chemical Biology, 2022, 18(8): 886-893. |
46 | RITTNER A, JOPPE M, SCHMIDT J J, et al. Chemoenzymatic synthesis of fluorinated polyketides[J]. Nature Chemistry, 2022, 14(9): 1000-1006. |
47 | LI Y, ZHANG W, ZHANG H, et al. Structural basis of a broadly selective acyltransferase from the polyketide synthase of splenocin[J]. Angewandte Chemie International Edition, 2018, 57(20): 5823-5827. |
48 | KALKREUTER E, CROWETIPTON J M, LOWELL A N, et al. Engineering the substrate specificity of a modular polyketide synthase for installation of consecutive non-natural extender units[J]. Journal of the American Chemical Society, 2019, 141(5): 1961-1969. |
49 | ENGLUND E, SCHMIDT M, NAVA A A, et al. Expanding extender substrate selection for unnatural polyketide biosynthesis by acyltransferase domain exchange within a modular polyketide synthase[J]. Journal of the American Chemical Society, 2023, 145(16): 8822-8832. |
50 | MUSIOL-KROLL E M, WOHLLEBEN W. Acyltransferases as tools for polyketide synthase engineering[J]. Antibiotics, 2018, 7(3): 62. |
51 | CHANG C C, HUANG R, YAN Y, et al. Uncovering the formation and selection of benzylmalonyl-CoA from the biosynthesis of splenocin and enterocin reveals a versatile way to introduce amino acids into polyketide carbon scaffolds[J]. Journal of the American Chemical Society, 2015, 137(12): 4183-4190. |
52 | ZHU X J, LIU J, ZHANG W J. De novo biosynthesis of terminal alkyne-labeled natural products[J]. Nature Chemical Biology, 2015, 11(2): 115-120. |
[1] | Zhehui HU, Juan XU, Guangkai BIAN. Application of automated high-throughput technology in natural product biosynthesis [J]. Synthetic Biology Journal, 2023, 4(5): 932-946. |
[2] | Fanzhong ZHANG, Changjun XIANG, Lihan ZHANG. Advances and applications of evolutionary analysis and big-data guided bioinformatics in natural product research [J]. Synthetic Biology Journal, 2023, 4(4): 629-650. |
[3] | Tao ZENG, Ruibo WU. Data-driven prediction and design for enzymatic reactions [J]. Synthetic Biology Journal, 2023, 4(3): 535-550. |
[4] | Liqi KANG, Pan TAN, Liang HONG. Enzyme engineering in the age of artificial intelligence [J]. Synthetic Biology Journal, 2023, 4(3): 524-534. |
[5] | Jiayu DONG, Min LI, Zonghua XIAO, Ming HU, Yudai MATSUDA, Weiguang WANG. Recent advances in heterologous production of natural products using Aspergillus oryzae [J]. Synthetic Biology Journal, 2022, 3(6): 1126-1149. |
[6] | Jingwei LYU, Zixin DENG, Qi ZHANG, Wei DING. Identification of RiPPs precursor peptides and cleavage sites based on deep learning [J]. Synthetic Biology Journal, 2022, 3(6): 1262-1276. |
[7] | Shiming TANG, Jiyuan HU, Suiping ZHENG, Shuangyan HAN, Ying LIN. Designing, building and rapid prototyping of biosynthesis module based on cell-free system [J]. Synthetic Biology Journal, 2022, 3(6): 1250-1261. |
[8] | Xinyu CUI, Ranran WU, Yuanming WANG, Zhiguang ZHU. Construction and enhancement of enzymatic bioelectrocatalytic systems [J]. Synthetic Biology Journal, 2022, 3(5): 1006-1030. |
[9] | Lu YANG, Xudong QU. Application of imine reductase in the synthesis of chiral amines [J]. Synthetic Biology Journal, 2022, 3(3): 516-529. |
[10] | Huibin WANG, Changli CHE, Song YOU. Recent advances of enzymatic synthesis of organohalogens catalyzed by Fe/αKG-dependent halogenases [J]. Synthetic Biology Journal, 2022, 3(3): 545-566. |
[11] | Jiaoyu JIN, Jiahai ZHOU. The mystery of Z-genome biosynthesis has been elucidated [J]. Synthetic Biology Journal, 2022, 3(1): 1-5. |
[12] | Jiuzhou CHEN, Yu WANG, Wei PU, Ping ZHENG, Jibin SUN. Advances and perspective on bioproduction of 5-aminolevulinic acid [J]. Synthetic Biology Journal, 2021, 2(6): 1000-1016. |
[13] | Xianglai LI, Xiaolin SHEN, Jia WANG, Qipeng YUAN, Xinxiao SUN. Recent advances in biosynthesis of chemicals by microbial co-culture [J]. Synthetic Biology Journal, 2021, 2(6): 876-885. |
[14] | Shuqi GUO, Ziyue JIAO, Qiang FEI. Progress in construction and applications of methanotrophic cell factory for chemicals biosynthesis [J]. Synthetic Biology Journal, 2021, 2(6): 1017-1029. |
[15] | Yichen WAN, Kongliang XU, Renchao ZHENG, Yuguo ZHENG. In vitro biosynthesis of chemicals: pathway design, component assembly and applications-a review [J]. Synthetic Biology Journal, 2021, 2(6): 886-901. |
Viewed | ||||||
Full text |
|
|||||
Abstract |
|
|||||