G e n o m e M in in g a n d M a r in e M ic r o b ia l N a t u r a l P r o d u c t s • Genome Mining K u i H o n g, C and Marine h a n g s h e n g Microbial Natural Z h a n g a n d A Products la n D o b s o n Edited by Kui Hong, Changsheng Zhang and Alan Dobson Printed Edition of the Special Issue Published in Marine Drugs www.mdpi.com/journal/marinedrugs Genome Mining and Marine Microbial Natural Products Genome Mining and Marine Microbial Natural Products SpecialIssueEditors KuiHong ChangshengZhang AlanDobson MDPI•Basel•Beijing•Wuhan•Barcelona•Belgrade SpecialIssueEditors KuiHong Changsheng Zhang Alan Dobson WuhanUniversity Chinese Academy of Sciences University College Cork China China Ireland EditorialOffice MDPI St.Alban-Anlage66 4052Basel,Switzerland This is a reprint of articles from the Special Issue published online in the open access journal MarineDrugs (ISSN 1660-3397) from 2017 to 2019 (available at: https://www.mdpi.com/journal/ marinedrugs/specialissues/genomemicrobe). Forcitationpurposes,citeeacharticleindependentlyasindicatedonthearticlepageonlineandas indicatedbelow: LastName,A.A.; LastName,B.B.; LastName,C.C.ArticleTitle. JournalNameYear,ArticleNumber, PageRange. ISBN978-3-03928-090-2(Pbk) ISBN978-3-03928-091-9(PDF) (cid:2)c 2019bytheauthors. ArticlesinthisbookareOpenAccessanddistributedundertheCreative Commons Attribution (CC BY) license, which allows users to download, copy and build upon publishedarticles,aslongastheauthorandpublisherareproperlycredited,whichensuresmaximum disseminationandawiderimpactofourpublications. ThebookasawholeisdistributedbyMDPIunderthetermsandconditionsoftheCreativeCommons licenseCCBY-NC-ND. Contents AbouttheSpecialIssueEditors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Prefaceto”GenomeMiningandMarineMicrobialNaturalProducts” . . . . . . . . . . . . . . ix Alka Choudhary, Lynn M. Naughton, Itxaso Monta´nchez, Alan D. W. Dobson and Dilip K. Rai Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials Reprintedfrom:Mar.Drugs2017,15,272,doi:10.3390/md15090272 . . . . . . . . . . . . . . . . . 1 ThomasE.Smith BiogeneticRelationshipsofBioactiveSpongeMerotriterpenoids Reprintedfrom:Mar.Drugs2017,15,285,doi:10.3390/md15090285 . . . . . . . . . . . . . . . . . 43 NajeebAkhter,YaqinLiu,BibiNaziaAuckloo,YutongShi,KuiwuWang,JuanjuanChen, XiaodanWuandBinWu Stress-Driven Discovery of New Angucycline-Type Antibiotics from a Marine StreptomycespratensisNA-ZhouS1 Reprintedfrom:Mar.Drugs2018,16,331,doi:10.3390/md16090331 . . . . . . . . . . . . . . . . . 66 PatriciaGo´mez-Villegas,JavierVigaraandRosaLeo´n Characterization of the Microbial Population Inhabiting a Solar Saltern Pond of the Odiel Marshlands(SWSpain) Reprintedfrom:Mar.Drugs2018,16,332,doi:10.3390/md16090332 . . . . . . . . . . . . . . . . . 82 LiLiao,ShiyuanSu,BinZhao,ChengqiFan,JinZhang,HuirongLiandBoChen BiosyntheticPotentialofaNovelAntarcticActinobacteriumMarisediminicolaantarcticaZS314T RevealedbyGenomicDataMiningandPigmentCharacterization Reprintedfrom:Mar.Drugs2019,17,388,doi:10.3390/md17070388 . . . . . . . . . . . . . . . . . 99 Wei Liu, Wenjun Zhang, Hongbo Jin, Qingbo Zhang, Yuchan Chen, Xiaodong Jiang, GuangtaoZhang,LipingZhang,WeiminZhang,ZhigangSheandChangshengZhang Genome Mining of Marine-Derived Streptomyces sp. SCSIO 40010 Leads to Cytotoxic New PolycyclicTetramateMacrolactams Reprintedfrom:Mar.Drugs2019,17,663,doi:10.3390/md17120663 . . . . . . . . . . . . . . . . . 114 LinXu,Kai-XiongYe,Wen-HuaDai,CongSun,Lian-HuaXuandBing-NanHan Comparative Genomic Insights into Secondary Metabolism Biosynthetic Gene Cluster DistributionsofMarineStreptomyces Reprintedfrom:Mar.Drugs2019,17,498,doi:10.3390/md17090498 . . . . . . . . . . . . . . . . . 128 YingYin,QiangFu,WenhuiWu,MenghaoCai,XiangshanZhouandYuanxingZhang Producing Novel Fibrinolytic Isoindolinone Derivatives in Marine Fungus Stachybotrys longispora FG216 by the Rational Supply of Amino Compounds According to ItsBiosynthesisPathway Reprintedfrom:Mar.Drugs2017,15,214,doi:10.3390/md15070214 . . . . . . . . . . . . . . . . . 146 XinZhen,TingGong,Yan-HuaWen,Dao-JiangYan,Jing-JingChenandPingZhu Chrysoxanthones A–C, Three New Xanthone–Chromanone Heterdimers from Sponge-AssociatedPenicilliumchrysogenumHLS111TreatedwithHistoneDeacetylaseInhibitor Reprintedfrom:Mar.Drugs2018,16,357,doi:10.3390/md16100357 . . . . . . . . . . . . . . . . . 159 v Mengjie Zhou, Fawang Liu, Xiaoyan Yang, Jing Jin, Xin Dong, Ke-Wu Zeng, Dong Liu, YingtaoZhang,MingMaandDonghuiYang BacillibactinandBacillomycinAnalogueswithCytotoxicitiesagainstHumanCancerCellLines fromMarineBacillussp.PKU-MA00093andPKU-MA00092 Reprintedfrom:Mar.Drugs2018,16,22,doi:10.3390/md16010022 . . . . . . . . . . . . . . . . . . 170 JingHou,JingLiu,LuYang,ZengzhiLiu,HuayueLi,QianChe,TianjiaoZhu,DehaiLiand WenliLi DiscoveryofanUnusualFattyAcidAmidefromthendgRyoGeneMutantofMarine-Derived Streptomycesyoussoufiensis Reprintedfrom:Mar.Drugs2019,17,12,doi:10.3390/md17010012 . . . . . . . . . . . . . . . . . . 184 vi About the Special Issue Editors KuiHongPh.D.,isaprofessorintheSchoolofPharmaceuticalSciences,WuhanUniversity,China. She has studied microbiology at Wuhan University, the South China College of Tropical Crops, Nanjing Agriculture University, and Tsinghua University, where she obtained her B.S., M.S. and Ph.D.degrees. Since2001,herresearchhasfocusedonmarinemicrobialdrugdiscovery,especially fromspecialmarineenvironmentssuchasmangroves,deepsea,andPolarRegions. Shehasledor participated in the national NSFC, “863,” “973,” and the EU “FP7” and China-Thai collaborative projects.SheisamemberoftheChineseMicrobiologySociety,ChineseBiochemistrySociety,Chinese Pharmacological Society, and Chinese Pharmaceutical Association. She possesses 19 national and 1PCTpatentsandpublishedmorethan100internationalpapers. Sheisnowthechiefscientistof the“NationalKeyR&DProgramofChina,”wheresheoverseesthesection“Highefficientdiscovery andmodificationofmarinemicrobialdrugcandidate”. Alan Dobson Ph.D., is Professor of Environmental Microbiology at University College Cork in Ireland.HestudiedbiochemistryattheNationalUniversityofIreland,Galway,whereheobtaineda B.Sc. in1981andaPh.D.in1985. HethenstudiedeukaryoticmolecularbiologyattheDepartment of Molecular and Cell Biology at Baylor College of Medicine before returning to the School of Microbiology at Cork. His group is focused on gaining a fuller understanding of how microbes survive, grow, and interact in their various ecological niches; an approach which is fundamental to their exploitation for biotechnological applications. He has to date published more than 190 peer-reviewedpapers.In1992,hewasawardedaFulbrightScholarshipandin1999,hereceivedthe RoyalIrishAcademyMedalinMicrobiologyforhisworkinenvironmentalmicrobiology. In2005, hewasawardedaD.Sc.inmicrobiologyandmolecularbiologybytheNationalUniversityofIreland inrecognitionofhiscontributionstoresearch.In2013,hewaselectedtotheRoyalIrishAcademy. ChangshengZhangPh.D., isaprofessorattheSouthChinaSeaInstituteofOceanology, Chinese AcademyofSciences,China. HeobtainedaB.Sc. inbiology(ShanghaiJiaotongUniversity,China, 1994)andanM.Sc.inbiotechnology(EastChinaUniversityofScienceandTechnology,1997).In2002, heobtainedhisPh.D.inchemicalmicrobiology(BergischeUniversityofWuppertal,Germany)with Prof. Dr. W. Piepersberg. He carried out postdoctoral research on natural product glycosylation studieswithJ.S.ThorsonatUniversityofWisconsin,Madison(2003–2008). In2008,hejoinedthe South China Sea Institute of Oceanology, China Academy of Sciences. His research interest is in marinemicrobialnaturalproductdiscoveryandbiosynthesis.Hehaspublishedmorethan90papers inpeer-reviewedjournalssuchasScience,NatureChemicalBiology,NatureCommunications,theJournal of American Chemical Society, and Angewandte Chemie. He is now an editorial member of Natural ProductReports. vii Preface to ”Genome Mining and Marine Microbial Natural Products” Most of the marine microbial natural products to date have been discovered using classical bioassay-guidedregimes. Thisprocessiscurrentlyundergoingsignificantchangesprimarilydueto ofrapiddevelopmentsinsequencingtechnology,syntheticbiology, andbioinformatics. However, as increasing numbers of whole-genome sequences become available, many genomes appear to possess“silent,”orcryptic,biosyntheticgeneclusters. Theproductsoftheseappeartoberegulated byavarietyofenvironmentalfactors,andthereforeremainlargelyundetected. Genomemininghas becomeaveryattractivetoolfordrugdiscoveryfrommarinemicroorganisms. Researchershavebeenusingdifferentstrategiestohelpactivatethesesilentgeneclustersfrom microbes, includingbutnotlimitedtobioinformatictoolsforgeneandgeneclusteridentification, geneeditingusingtheinnovativeCRISPRCas9technology,heterologousexpressionbasedstrategies, aswellasactivationusingenvironmentalfactors.Wearegladtoseethatthesestrategiesarealsobeing employedonmarinemicrobes,whichwillhelpinthediscoveryofmoreandmorenewcompounds. ThisSpecialIssueprovidesanumberofinterestingexamplesofsomeoftheexcellentworkthatis currentlybeingundertakeninthisarena.Italsohintsatthelikelihoodofmajoradvancesinthisfield intheverynearfuture. KuiHong,ChangshengZhang,AlanDobson SpecialIssueEditors ix