An overview on reconstructing the biosynthetic system of actinomycetes for polyketides production

XIE Huang; ZHENG Yilei; SU Yiting; RUAN Jingyi; LI Yongquan

doi:10.12211/2096-8280.2023-087

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An overview on reconstructing the biosynthetic system of actinomycetes for polyketides production

Invited Review | 更新时间：2025-03-19

- An overview on reconstructing the biosynthetic system of actinomycetes for polyketides production
- Synthetic Biology Journal Vol. 5, Issue 3, Pages: 612-630(2024)
- 作者机构：
  
  1.浙江大学药物生物技术研究所，浙江杭州 310058
  2.浙江省微生物生化与代谢工程重点实验室，浙江杭州 310058
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2023-087
  CLC： Q939.97
- Received：28 November 2023，
  
  Revised：2024-01-16，
  
  Published：30 June 2024
- 稿件说明：
移动端阅览
谢皇，郑义蕾，苏依婷，阮静怡，李永泉. 放线菌聚酮类化合物生物合成体系重构研究进展［J］. 合成生物学， 2024， 5（3）： 612-630

XIE Huang， ZHENG Yilei， SU Yiting， RUAN Jingyi， LI Yongquan. An overview on reconstructing the biosynthetic system of actinomycetes for polyketides production［J］. Synthetic Biology Journal， 2024， 5（3）： 612-630
谢皇，郑义蕾，苏依婷，阮静怡，李永泉. 放线菌聚酮类化合物生物合成体系重构研究进展［J］. 合成生物学， 2024， 5（3）： 612-630 DOI： 10.12211/2096-8280.2023-087.

XIE Huang， ZHENG Yilei， SU Yiting， RUAN Jingyi， LI Yongquan. An overview on reconstructing the biosynthetic system of actinomycetes for polyketides production［J］. Synthetic Biology Journal， 2024， 5（3）： 612-630 DOI： 10.12211/2096-8280.2023-087.

摘要

放线菌因其丰富的次级代谢产物而成为候选药物发掘的宝贵资源库，其蕴含的活性化合物包含聚酮类、非核糖体肽类、氨基糖苷类、萜类等，其中聚酮类化合物占比最大。大环内酯是聚酮类化合物的典型，常常被用作抗生素、抗肿瘤剂、免疫抑制剂、抗寄生虫剂等，具有重要的生物学意义。本文立足聚酮类大环内酯的生物合成过程，提出了从基因组重塑、调控通路重组、组合代谢工程及聚酮类化合物结构的衍生与多样化等多角度，实现放线菌聚酮类生物合成体系的优化，为工业规模生产聚酮类药物及其新型衍生物提供技术支撑。通过这种多维度的方法，结合最新的合成生物学使能技术，遵循绿色、环保、高效和可持续的策略，可以更有效地优化和增强放线菌中聚酮类化合物的生产，为未来药物的开发和生产提供新的可能性。

Abstract

Actinomycetes

enriched with secondary metabolites

have emerged as a resource for drug discovery. These organisms predominantly harbor bioactive compounds such as polyketides

non-ribosomal peptides

aminoglycosides

and terpenes

with polyketides representing the most diverse class. Polyketides are divided into three major categories based on polyketide synthase: type Ⅰ

type Ⅱ

and type Ⅲ

in which type Ⅰ polyketides are most widely distributed and abundant

with macrocyclic lactone compounds serving as their archetypal representatives. Macrocyclic lactone compounds

frequently utilized as antibiotics

anti-cancer agents

immunosuppressants

and antiparasitic agents

hold immense biological significance. This review comments the biosynthetic process of macrolides

and strategies for biosynthesizing actinomycete polyketides are proposed

which encompass genome remodeling

regulatory pathway recombination

combinatorial metabolic engineering

and the modifications of polyketide structures. By knocking out competing gene clusters and superfluous genomic islands

augmenting the supply of precursors

and enhancing precursor supply and lipid stream processing

researchers can obtain genome-minimized and optimized industrial chassis

followed with manipulations such as promoter engineering

regulatory factor engineering

overexpression of the rate-limiting enzyme genes

enhanced substrate transport and tolerance

targeted modifications of the key enzymes

rational design of polyketides

etc

. Furthermore

the optimized chassis and biosynthetic gene clusters are integrated to develop robust strains for multi-omics analyses and fermentation process optimization

which can be guided by rapidly developed synthetic biology enabling technologies and artificial intelligence

to develop a

high-quality

efficient polyketides biosynthesis system. These advancements can offer robust technical support for the large-scale production of polyketides pharmaceuticals and their derivatives.

关键词

Keywords

references

WAKSMAN S A , REILLY H C , JOHNSTONE D B . Isolation of streptomycin-producing strains of Streptomyces griseus [J ] . Journal of Bacteriology , 1946 , 52 ( 3 ): 393 - 397 .

MARSCHNER P . Rhizosphere biology [M/OL ] // Marschner’s mineral nutrition of higher plants . 3rd Edition . New York : Academic Press , 2012 : 369 - 388 [2023-12-01] . https://www.sciencedirect.com/science/article/abs/pii/B9780123849052000157 https://www.sciencedirect.com/science/article/abs/pii/B9780123849052000157 .

NETT M , IKEDA H , MOORE B S . Genomic basis for natural product biosynthetic diversity in the actinomycetes [J ] . Natural Product Reports , 2009 , 26 ( 11 ): 1362 - 1384 .

KOMAKI H , SAKURAI K , HOSOYAMA A , et al . Diversity of nonribosomal peptide synthetase and polyketide synthase gene clusters among taxonomically close Streptomyces strains [J ] . Scientific Reports , 2018 , 8 ( 1 ): 6888 .

BELKNAP K C , PARK C J , BARTH B M , et al . Genome mining of biosynthetic and chemotherapeutic gene clusters in Streptomyces bacteria [J ] . Scientific Reports , 2020 , 10 ( 1 ): 2003 .

HE X M , LIU H W . Formation of unusual sugars: mechanistic studies and biosynthetic applications [J ] . Annual Review of Biochemistry , 2002 , 71 : 701 - 754 .

DUTTA S , WHICHER J R , HANSEN D A , et al . Structure of a modular polyketide synthase [J ] . Nature , 2014 , 510 ( 7506 ): 512 - 517 .

WHICHER J R , DUTTA S , HANSEN D A , et al . Structural rearrangements of a polyketide synthase module during its catalytic cycle [J ] . Nature , 2014 , 510 ( 7506 ): 560 - 564 .

PARK S R , HAN A R , BAN Y H , et al . Genetic engineering of macrolide biosynthesis: past advances, current state, and future prospects [J ] . Applied Microbiology and Biotechnology , 2010 , 85 ( 5 ): 1227 - 1239 .

CHEN A Y , SCHNARR N A , KIM C Y , et al . Extender unit and acyl carrier protein specificity of ketosynthase domains of the 6-deoxyerythronolide B synthase [J ] . Journal of the American Chemical Society , 2006 , 128 ( 9 ): 3067 - 3074 .

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 .

XU W , QIAO K J , TANG Y . Structural analysis of protein-protein interactions in type Ⅰ polyketide synthases [J ] . Critical Reviews in Biochemistry and Molecular Biology , 2013 , 48 ( 2 ): 98 - 122 .

XIAO Y , LI S M , NIU S W , et al . Characterization of tiacumicin B biosynthetic gene cluster affording diversified tiacumicin analogues and revealing a tailoring dihalogenase [J ] . Journal of the American Chemical Society , 2011 , 133 ( 4 ): 1092 - 1105 .

ERB W , ZHU J P . From natural product to marketed drug: the tiacumicin odyssey [J ] . Natural Product Reports , 2013 , 30 ( 1 ): 161 - 174 .

LI Y P , YU P , LI J F , et al . FadR1, a pathway-specific activator of fidaxomicin biosynthesis in Actinoplanes deccanensis Yp-1 [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 18 ): 7583 - 7596 .

MYRONOVSKYI M , ROSENKRÄNZER B , NADMID S , et al . Generation of a cluster-free Streptomyces albus chassis strains for improved heterologous expression of secondary metabolite clusters [J ] . Metabolic Engineering , 2018 , 49 : 316 - 324 .

GOMEZ-ESCRIBANO J P , BIBB M J . Engineering Streptomyces coelicolor for heterologous expression of secondary metabolite gene clusters [J ] . Microbial Biotechnology , 2011 , 4 ( 2 ): 207 - 215 .

JONES A C , GUST B , KULIK A , et al . Phage p1-derived artificial chromosomes facilitate heterologous expression of the FK506 gene cluster [J ] . PLoS One , 2013 , 8 ( 7 ): e69319 .

NAH H J , WOO M W , CHOI S S , et al . Precise cloning and tandem integration of large polyketide biosynthetic gene cluster using Streptomyces artificial chromosome system [J ] . Microbial Cell Factories , 2015 , 14 : 140 .

TANG X Y , LI J , MILLÁN-AGUIÑAGA N , et al . Identification of thiotetronic acid antibiotic biosynthetic pathways by target-directed genome mining [J ] . ACS Chemical Biology , 2015 , 10 ( 12 ): 2841 - 2849 .

QIAN Z Y , BRUHN T , D’AGOSTINO P M , et al . Discovery of the streptoketides by direct cloning and rapid heterologous expression of a cryptic PKS Ⅱ gene cluster from Streptomyces sp. Tü 6314 [J ] . The Journal of Organic Chemistry , 2020 , 85 ( 2 ): 664 - 673 .

GREN T , WHITFORD C M , MOHITE O S , et al . Characterization and engineering of Streptomyces griseofuscus DSM 40191 as a potential host for heterologous expression of biosynthetic gene clusters [J ] . Scientific Reports , 2021 , 11 ( 1 ): 18301 .

BLIN K , SHAW S , KLOOSTERMAN A M , et al . antiSMASH 6.0: improving cluster detection and comparison capabilities [J ] . Nucleic Acids Research , 2021 , 49 ( W1 ): W29 - W35 .

LU C Y , ZHANG X J , JIANG M , et al . Enhanced salinomycin production by adjusting the supply of polyketide extender units in Streptomyces albus [J ] . Metabolic Engineering , 2016 , 35 : 129 - 137 .

KORMANEC J , REZUCHOVA B , HOMEROVA D , et al . Recent achievements in the generation of stable genome alterations/mutations in species of the genus Streptomyces [J ] . Applied Microbiology and Biotechnology , 2019 , 103 ( 14 ): 5463 - 5482 .

CRAMERI R , KIESER T , ONO H , et al . Chromosomal instability in Streptomyces glaucescens : mapping of streptomycin-sensitive mutants [J ] . Microbiology , 1983 , 129 ( 2 ): 519 - 527 .

PENG M X , LIANG Z H . Degeneration of industrial bacteria caused by genetic instability [J ] . World Journal of Microbiology & Biotechnology , 2020 , 36 ( 8 ): 119 .

FISHMAN S E , HERSHBERGER C L . Amplified DNA in Streptomyces fradiae [J ] . Journal of Bacteriology , 1983 , 155 ( 2 ): 459 - 466 .

ROTH M , NOACK D . Genetic stability of differentiated functions in Streptomyces hygroscopicus in relation to conditions of continuous culture [J ] . Microbiology , 1982 , 128 ( 1 ): 107 - 114 .

LI Y P , BU Q T , LI J F , et al . Genome-based rational engineering of Actinoplanes deccanensis for improving fidaxomicin production and genetic stability [J ] . Bioresource Technology , 2021 , 330 : 124982 .

BU Q T , YU P , WANG J , et al . Rational construction of genome-reduced and high-efficient industrial Streptomyces chassis based on multiple comparative genomic approaches [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 16 .

GOMEZ-ESCRIBANO J P , BIBB M J . Streptomyces coelicolor as an expression host for heterologous gene clusters [J ] . Methods in Enzymology , 2012 , 517 : 279 - 300 .

JUGUET M , LAUTRU S , FRANCOU F X , et al . An iterative nonribosomal peptide synthetase assembles the pyrrole-amide antibiotic congocidine in Streptomyces ambofaciens [J ] . Chemistry & Biology , 2009 , 16 ( 4 ): 421 - 431 .

IKEDA H , KAZUO S Y , OMURA S . Genome mining of the Streptomyces avermitilis genome and development of genome-minimized hosts for heterologous expression of biosynthetic gene clusters [J ] . Journal of Industrial Microbiology & Biotechnology , 2014 , 41 ( 2 ): 233 - 250 .

KOMATSU M , KOMATSU K , KOIWAI H , et al . Engineered Streptomyces avermitilis host for heterologous expression of biosynthetic gene cluster for secondary metabolites [J ] . ACS Synthetic Biology , 2013 , 2 ( 7 ): 384 - 396 .

LOPATNIUK M , MYRONOVSKYI M , LUZHETSKYY A . Streptomyces albus : a new cell factory for non-canonical amino acids incorporation into ribosomally synthesized natural products [J ] . ACS Chemical Biology , 2017 , 12 ( 9 ): 2362 - 2370 .

BATE N , STRATIGOPOULOS G , CUNDLIFFE E . Differential roles of two SARP-encoding regulatory genes during tylosin biosynthesis [J ] . Molecular Microbiology , 2002 , 43 ( 2 ): 449 - 458 .

AIGLE B , PANG X H , DECARIS B , et al . Involvement of AlpV, a new member of the Streptomyces antibiotic regulatory protein family, in regulation of the duplicated type Ⅱ polyketide synthase alp gene cluster in Streptomyces ambofaciens [J ] . Journal of Bacteriology , 2005 , 187 ( 7 ): 2491 - 2500 .

YIN S L , WANG W S , WANG X F , et al . Identification of a cluster-situated activator of oxytetracycline biosynthesis and manipulation of its expression for improved oxytetracycline production in Streptomyces rimosus [J ] . Microbial Cell Factories , 2015 , 14 : 46 .

ZHANG Y Y , HE H R , LIU H , et al . Characterization of a pathway-specific activator of milbemycin biosynthesis and improved milbemycin production by its overexpression in Streptomyces bingchenggensis [J ] . Microbial Cell Factories , 2016 , 15 ( 1 ): 152 .

ZHANG X S , LUO H D , TAO Y , et al . FkbN and Tcs7 are pathway-specific regulators of the FK506 biosynthetic gene cluster in Streptomyces tsukubaensis L19 [J ] . Journal of Industrial Microbiology & Biotechnology , 2016 , 43 ( 12 ): 1693 - 1703 .

ANTÓN N , MENDES M V , MARTÍN J F , et al . Identification of PimR as a positive regulator of pimaricin biosynthesis in Streptomyces natalensis [J ] . Journal of Bacteriology , 2004 , 186 ( 9 ): 2567 - 2575 .

WILSON D J , XUE Y , REYNOLDS K A , et al . Characterization and analysis of the PikD regulatory factor in the pikromycin biosynthetic pathway of Streptomyces venezuelae [J ] . Journal of Bacteriology , 2001 , 183 ( 11 ): 3468 - 3475 .

ZHU Z H , LI H , YU P , et al . SlnR is a positive pathway-specific regulator for salinomycin biosynthesis in Streptomyces albus [J ] . Applied Microbiology and Biotechnology , 2017 , 101 ( 4 ): 1547 - 1557 .

KUSCER E , COATES N , CHALLIS I , et al . Roles of rapH and rapG in positive regulation of rapamycin biosynthesis in Streptomyces hygroscopicus [J ] . Journal of Bacteriology , 2007 , 189 ( 13 ): 4756 - 4763 .

PARK S S , YANG Y H , SONG E , et al . Mass spectrometric screening of transcriptional regulators involved in antibiotic biosynthesis in Streptomyces coelicolor A3(2) [J ] . Journal of Industrial Microbiology & Biotechnology , 2009 , 36 ( 8 ): 1073 - 1083 .

MAO X M , LUO S , ZHOU R C , et al . Transcriptional regulation of the daptomycin gene cluster in Streptomyces roseosporus by an autoregulator, AtrA [J ] . The Journal of Biological Chemistry , 2015 , 290 ( 12 ): 7992 - 8001 .

YU P , LIU S P , BU Q T , et al . WblAch, a pivotal activator of natamycin biosynthesis and morphological differentiation in Streptomyces chattanoogensis L10, is positively regulated by AdpAch [J ] . Applied and Environmental Microbiology , 2014 , 80 ( 22 ): 6879 - 6887 .

FU Y , DONG Y Q , SHEN J L , et al . A meet-up of acetyl phosphate and c-di-GMP modulates BldD activity for development and antibiotic production [J ] . Nucleic Acids Research , 2023 , 51 ( 13 ): 6870 - 6882 .

MARTÍN J F , LIRAS P , SÁNCHEZ S . Modulation of gene expression in Actinobacteria by translational modification of transcriptional factors and secondary metabolite biosynthetic enzymes [J ] . Frontiers in Microbiology , 2021 , 12 : 630694 .

DE CRÉCY-LAGARD V , SERVANT-MOISSON P , VIALA J , et al . Alteration of the synthesis of the Clp ATP-dependent protease affects morphological and physiological differentiation in Streptomyces [J ] . Molecular Microbiology , 1999 , 32 ( 3 ): 505 - 517 .

MAO X M , SUN N , WANG F , et al . Dual positive feedback regulation of protein degradation of an extra-cytoplasmic function σ factor for cell differentiation in Streptomyces coelicolor [J ] . The Journal of Biological Chemistry , 2013 , 288 ( 43 ): 31217 - 31228 .

MAO X M , REN N N , SUN N , et al . Proteasome involvement in a complex cascade mediating SigT degradation during differentiation of Streptomyces coelicolor [J ] . FEBS Letters , 2014 , 588 ( 4 ): 608 - 613 .

SHEN J J , CHEN F , WANG X X , et al . Substrate specificity of acyltransferase domains for efficient transfer of acyl groups [J ] . Frontiers in Microbiology , 2018 , 9 : 1840 .

STUTZMAN-ENGWALL K , CONLON S , FEDECHKO R , et al . Semi-synthetic DNA shuffling of aveC leads to improved industrial scale production of doramectin by Streptomyces avermitilis [J ] . Metabolic Engineering , 2005 , 7 ( 1 ): 27 - 37 .

GRABOWSKA A D , BRISON Y , MAVEYRAUD L , et al . Molecular basis for extender unit specificity of mycobacterial polyketide synthases [J ] . ACS Chemical Biology , 2020 , 15 ( 12 ): 3206 - 3216 .

INGRAHAM J B , BARANOV M , COSTELLO Z , et al . Illuminating protein space with a programmable generative model [J ] . Nature , 2023 , 623 ( 7989 ): 1070 - 1078 .

BOIKO D A , MACKNIGHT R , KLINE B , et al . Autonomous chemical research with large language models [J ] . Nature , 2023 , 624 ( 7992 ): 570 - 578 .

BERQUEZ M , CHEN Z Y , FESTA B P , et al . Lysosomal cystine export regulates mTORC1 signaling to guide kidney epithelial cell fate specialization [J ] . Nature Communications , 2023 , 14 ( 1 ): 3994 .

SUN J , KELEMEN G H , FERNÁNDEZ-ABALOS J M , et al . Green fluorescent protein as a reporter for spatial and temporal gene expression in Streptomyces coelicolor A3(2) [J ] . Microbiology , 1999 , 145 ( Pt 9 ): 2221 - 2227 .

MYRONOVSKYI M , WELLE E , FEDORENKO V , et al . β-glucuronidase as a sensitive and versatile reporter in actinomycetes [J ] . Applied and Environmental Microbiology , 2011 , 77 ( 15 ): 5370 - 5383 .

ZHENG J T , SAGAR V , SMOLINSKY A , et al . Structure and function of the macrolide biosensor protein, MphR(A), with and without erythromycin [J ] . Journal of Molecular Biology , 2009 , 387 ( 5 ): 1250 - 1260 .

CHEN Y , DENG W , WU J Q , et al . Genetic modulation of the overexpression of tailoring genes eryK and eryG leading to the improvement of erythromycin A purity and production in Saccharopolyspora erythraea fermentation [J ] . Applied and Environmental Microbiology , 2008 , 74 ( 6 ): 1820 - 1828 .

ZHANG J , HE Z L , XU J T , et al . Semi-rational mutagenesis of an industrial Streptomyces fungicidicus strain for improved enduracidin productivity [J ] . Applied Microbiology and Biotechnology , 2020 , 104 ( 8 ): 3459 - 3471 .

CHEN H T , ZHANG X Y , WU Q B , et al . Production improvement of FK506 in Streptomyces tsukubaensis by metabolic engineering strategy [J ] . Journal of Applied Microbiology , 2023 , 134 ( 7 ): lxad142 .

LI L , WEI K K , LIU X C , et al . aMSGE: advanced multiplex site-specific genome engineering with orthogonal modular recombinases in actinomycetes [J ] . Metabolic Engineering , 2019 , 52 : 153 - 167 .

MURAKAMI T , SUMIDA N , BIBB M , et al . ZouA, a putative relaxase, is essential for DNA amplification in Streptomyces kanamyceticus [J ] . Journal of Bacteriology , 2011 , 193 ( 8 ): 1815 - 1822 .

MURAKAMI T , BURIAN J , YANAI K , et al . A system for the targeted amplification of bacterial gene clusters multiplies antibiotic yield in Streptomyces coelicolor [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2011 , 108 ( 38 ): 16020 - 16025 .

SHAN Y M , GUO D , GU Q S , et al . Genome min ing and homologous comparison strategy for digging exporters contributing self-resistance in natamycin-producing Streptomyces strains [J ] . Applied Microbiology and Biotechnology , 2020 , 104 ( 2 ): 817 - 831 .

QIU J F , ZHUO Y , ZHU D Q , et al . Overexpression of the ABC transporter AvtAB increases avermectin production in Streptomyces avermitilis [J ] . Applied Microbiology and Biotechnology , 2011 , 92 ( 2 ): 337 - 345 .

YU L , YAN X Y , WANG L , et al . Molecular cloning and functional characterization of an ATP-binding cassette transporter OtrC from Streptomyces rimosus [J ] . BMC Biotechnology , 2012 , 12 : 52 .

WANG X R , WEI J H , XIAO Y F , et al . Efflux identification and engineering for ansamitocin P-3 production in Actinosynnema pretiosum [J ] . Applied Microbiology and Biotechnology , 2021 , 105 ( 2 ): 695 - 706 .

CHU L Y , LI S S , DONG Z X , et al . Mining and engineering exporters for titer improvement of macrolide biopesticides in Streptomyces [J ] . Microbial Biotechnology , 2022 , 15 ( 4 ): 1120 - 1132 .

ROKEM J S , LANTZ A E , NIELSEN J . Systems biology of antibiotic production by microorganisms [J ] . Natural Product Reports , 2007 , 24 ( 6 ): 1262 - 1287 .

KIM E , MOORE B S , YOON Y J . Reinvigorating natural product combinatorial biosynthesis with synthetic biology [J ] . Nature Chemical Biology , 2015 , 11 ( 9 ): 649 - 659 .

BREITLING R , TAKANO E . Synthetic biology of natural products [J ] . Cold Spring Harbor Perspectives in Biology , 2016 , 8 ( 10 ): a023994 .

MICHAEL J B , PER B , SRDJAN J , et al . Engineering of Primary carbon metabolism for improved antibiotic production in Streptomyces lividans [J ] . Applied and Environmental Microbiology , 2002 , 68 ( 10 ): 4731 - 4739 .

ZABALA D , BRAÑA A F , FLÓREZ A B , et al . Engineering precursor metabolite pools for increasing production of antitumor mithramycins in Streptomyces argillaceus [J ] . Metabolic Engineering , 2013 , 20 : 187 - 197 .

HUANG D , LI S S , XIA M L , et al . Genome-scale metabolic network guided engineering of Streptomyces tsukubaensis for FK506 production improvement [J ] . Microbial Cell Factories , 2013 , 12 : 52 .

DANG L Q , LIU J , WANG C , et al . Enhancement of rapamycin production by metabolic engineering in Streptomyces hygroscopicus based on genome-scale metabolic model [J ] . Journal of Industrial Microbiology & Biotechnology , 2017 , 44 ( 2 ): 259 - 270 .

BAI C X , ZHANG Y , ZHAO X J , et al . Exploiting a precise design of universal synthetic modular regulatory elements to unlock the microbial natural products in Streptomyces [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2015 , 112 ( 39 ): 12181 - 12186 .

WANG T , BAI L Q , ZHU D Q , et al . Enhancing macrolide production in Streptomyces by coexpressing three heterologous genes [J ] . Enzyme and Microbial Technology , 2012 , 50 ( 1 ): 5 - 9 .

GERTH K , BEDORF N , HÖFLE G , et al . Epothilons A and B: antifungal and cytotoxic compounds from Sorangium cellulosum (Myxobacteria). Production, physico-chemical and biological properties [J ] . The Journal of Antibiotics , 1996 , 49 ( 6 ): 560 - 563 .

GRIFFITH R S , BLACK H R . Erythromycin [J ] . The Medical Clinics of North America , 1970 , 54 ( 5 ): 1199 - 1215 .

DUTCHER J D . The discovery and development of amphotericin B [J ] . Diseases of the Chest , 1968 , 54 : 296 - 298 .

KUHSTOSS S , HUBER M , TURNER J R , et al . Production of a novel polyketide through the construction of a hybrid polyketide synthase [J ] . Gene , 1996 , 183 ( 1-2 ): 231 - 236 .

LONG P F , WILKINSON C J , BISANG C P , et al . Engineering specificity of starter unit selection by the erythromycin-producing polyketide synthase [J ] . Molecular Microbiology , 2002 , 43 ( 5 ): 1215 - 1225 .

DUTTON C J , GIBSON S P , GOUDIE A C , et al . Novel avermectins produced by mutational biosynthesis [J ] . The Journal of Antibiotics , 1991 , 44 ( 3 ): 357 - 365 .

YUZAWA S , ENG C H , KATZ L , et al . Broad substrate specificity of the loading didomain of the lipomycin polyketide synthase [J ] . Biochemistry , 2013 , 52 ( 22 ): 3791 - 3793 .

MUSIOL-KROLL E M , ZUBEIL F , SCHAFHAUSER T , et al . Polyketide bioderivatization using the promiscuous acyltransferase KirCⅡ [J ] . ACS Synthetic Biology , 2017 , 6 ( 3 ): 421 - 427 .

REEVES C D , MURLI S , ASHLEY G W , et al . Alteration of the substrate specificity of a modular polyketide synthase acyltransferase domain through site-specific mutations [J ] . Biochemistry , 2001 , 40 ( 51 ): 15464 - 15470 .

沈洁洁 , 毛旭明 , 陈新爱 , 等 . Ⅰ型聚酮合酶中酰基转移酶结构域的研究进展 [J ] . 有机化学 , 2018 , 38 ( 9 ): 2377 - 2385 .

SHEN J J , MAO X M , CHEN X A , et al . Recent advances in acyltransferase domain of type Ⅰ polyktide synthases [J ] . Chinese Journal of Organic Chemistry , 2018 , 38 ( 9 ): 2377 - 2385 .

MARSDEN A F , WILKINSON B , CORTÉS J , et al . Engineering broader specificity into an antibiotic-producing polyketide synthase [J ] . Science , 1998 , 279 ( 5348 ): 199 - 202 .

STASSI D L , KAKAVAS S J , REYNOLDS K A , et al . Ethyl-substituted erythromycin derivatives produced by directed metabolic engineering [J ] . Proceedings of the National Academy of Sciences of the United States of America , 1998 , 95 ( 13 ): 7305 - 7309 .

HANS M , HORNUNG A , DZIARNOWSKI A , et al . Mechanistic analysis of acyl transferase domain exchange in polyketide synthase modules [J ] . Journal of the American Chemical Society , 2003 , 125 ( 18 ): 5366 - 5374 .

MUSIOL E M , WEBER T . Discrete acyltransferases involved in polyketide biosynthesis [J ] . MedChemComm , 2012 , 3 ( 8 ): 871 - 886 .

BARAJAS J F , BLAKE-HEDGES J M , BAILEY C B , et al . Engineered polyketides: synergy between protein and host level engineering [J ] . Synthetic and Systems Biotechnology , 2017 , 2 ( 3 ): 147 - 166 .

PETKOVIĆ H , SANDMANN A , CHALLIS I R , et al . Substrate specificity of the acyl transferase domains of EpoC from the epothilone polyketide synthase [J ] . Organic & Biomolecular Chemistry , 2008 , 6 ( 3 ): 500 - 506 .

JIANG H , WANG Y Y , GUO Y Y , et al . An acyltransferase domain of FK506 polyketide synthase recognizing both an acyl carrier protein and coenzyme A as acyl donors to transfer allylmalonyl and ethylmalonyl units [J ] . The FEBS Journal , 2015 , 282 ( 13 ): 2527 - 2539 .

SUNDERMANN U , BRAVO-RODRIGUEZ K , KLOPRIES S , et al . Enzyme-directed mutasynthesis: a combined experimental and theoretical approach to substrate recognition of a polyketide synthase [J ] . ACS Chemical Biology , 2013 , 8 ( 2 ): 443 - 450 .

BRAVO-RODRIGUEZ K , ISMAIL-ALI A F , KLOPRIES S , et al . Predicted incorporation of non-native substrates by a polyketide synthase yields bioactive natural product derivatives [J ] . ChemBioChem , 2014 , 15 ( 13 ): 1991 - 1997 .

BAERGA-ORTIZ A , POPOVIC B , SISKOS A P , et al . Directed mutagenesis alters the stereochemistry of catalysis by isolated ketoreductase domains from the erythromycin polyketide synthase [J ] . Chemistry & Biology , 2006 , 13 ( 3 ): 277 - 285 .

O′HARE H M , BAERGA-ORTIZ A , POPOVIC B , et al . High-throughput mutagenesis to evaluate models of stereochemical control in ketoreductase domains from the erythromycin polyketide synthase [J ] . Chemistry & Biology , 2006 , 13 ( 3 ): 287 - 296 .

REID R , PIAGENTINI M , RODRIGUEZ E , et al . A model of structure and catalysis for ketoreductase domains in modular polyketide synthases [J ] . Biochemistry , 2003 , 42 ( 1 ): 72 - 79 .

ZHOU Y J , LI J L , ZHU J , et al . Incomplete β-ketone processing as a mechanism for polyene structural variation in the FR-008/candicidin complex [J ] . Chemistry & Biology , 2008 , 15 ( 6 ): 629 - 638 .

BRAUTASET T , SLETTA H , NEDAL A , et al . Improved antifungal polyene macrolides via engineering of the nystatin biosynthetic genes in Streptomyces noursei [J ] . Chemistry & Biology , 2008 , 15 ( 11 ): 1198 - 1206 .

YONG J H , BYEON W H . Alternative production of avermectin components in Streptomyces avermitilis by gene replacement [J ] . Journal of Microbiology , 2005 , 43 ( 3 ): 277 - 284 .

KEATINGE-CLAY A T . Stereocontrol within polyketide assembly lines [J ] . Natural Product Reports , 2016 , 33 ( 2 ): 141 - 149 .

KWAN D H , SUN Y H , SCHULZ F , et al . Prediction and manipulation of the stereochemistry of enoylreduction in modular polyketide synthases [J ] . Chemistry & Biology , 2008 , 15 ( 11 ): 1231 - 1240 .

QI Z , ZHOU Y C , KANG Q J , et al . Directed accumulation of less toxic pimaricin derivatives by improving the efficiency of a polyketide synthase dehydratase domain [J ] . Applied Microbiology and Biotechnology , 2017 , 101 ( 6 ): 2427 - 2436 .

ZHANG X L , CHEN Z , LI M , et al . Construction of ivermectin producer by domain swaps of avermectin polyketide synthase in Streptomyces avermitilis [J ] . Applied Microbiology and Biotechnology , 2006 , 72 ( 5 ): 986 - 994 .

MCDANIEL R , THAMCHAIPENET A , GUSTAFSSON C , et al . Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel “unnatural” natural products [J ] . Proceedings of the National Academy of Sciences of the United States of America , 1999 , 96 ( 5 ): 1846 - 1851 .

CORTES J , WIESMANN K E , ROBERTS G A , et al . Repositioning of a domain in a modular polyketide synthase to promote specific chain cleavage [J ] . Science , 1995 , 268 ( 5216 ): 1487 - 1489 .

PIEPER R , GOKHALE R S , LUO G , et al . Purification and characterization of bimodular and trimodular derivatives of the erythromycin polyketide synthase [J ] . Biochemistry , 1997 , 36 ( 7 ): 1846 - 1851 .

WEISSMAN K J , BYCROFT M , STAUNTON J , et al . Origin of starter units for erythromycin biosynthesis [J ] . Biochemistry , 1998 , 37 ( 31 ): 11012 - 11017 .

ENGLUND E , SCHMIDT M , NAVA A A , et al . Biosensor guided polyketide synthases engineering for optimization of domain exchange boundaries [J ] . Nature Communications , 2023 , 14 ( 1 ): 4871 .

HOCHLOWSKI J E , JACKSON M , RASMUSSEN R R , et al . Production of brominated tiacumicin derivatives [J ] . The Journal of Antibiotics , 1997 , 50 ( 3 ): 201 - 205 .

GROTE M , SCHULZ F . Exploring the promiscuous enzymatic activation of unnatural polyketide extender units in vitro and in vivo for monensin biosynthesis [J ] . ChemBioChem , 2019 , 20 ( 9 ): 1183 - 1189 .

ZHANG H B , TIAN X X , PU X H , et al . Tiacumicin congeners with improved antibacterial activity from a halogenase-inactivated mutant [J ] . Journal of Natural Products , 2018 , 81 ( 5 ): 1219 - 1224 .

MALMIERCA M G , PÉREZ-VICTORIA I , MARTÍN J , et al . New sipanmycin analogues generated by combinatorial biosynthesis and mutasynthesis approaches relying on the substrate flexibility of key enzymes in the biosynthetic pathway [J ] . Applied and Environmental Microbiology , 2020 , 86 ( 3 ): e02453-19 .

LI L Y , HU Y L , SUN J L , et al . Resistance and phylogeny guided discovery reveals structural novelty of tetracycline antibiotics [J ] . Chemical Science , 2022 , 13 ( 43 ): 12892 - 12898 .

DHAKAL D , SOHNG J K , PANDEY R P . Engineering actinomycetes for biosynthesis of macrolactone polyketides [J ] . Microbial Cell Factories , 2019 , 18 ( 1 ): 137 .

YUAN Y J , CHENG S , BIAN G K , et al . Efficient exploration of terpenoid biosynthetic gene clusters in filamentous fungi [J ] . Nature Catalysis , 2022 , 5 ( 4 ): 277 - 287 .

DENG L , ZHAO Z H , LIU L , et al . Dissection of 3D chromosome organization in Streptomyces coelicolor A3(2) leads to biosynthetic gene cluster overexpression [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2023 , 120 ( 11 ): e2222045120 .

TU R , ZHANG Y , HUA E B , et al . Droplet-based microfluidic platform for high-throughput screening of Streptomyces [J ] . Communications Biology , 2021 , 4 ( 1 ): 647 .

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