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Diversity of Linear Non-Ribosomal Peptide in Biocontrol Fungi

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Diversity of Linear Non-Ribosomal Peptide in Biocontrol Fungi Journal of Fungi Review Diversity of Linear Non-Ribosomal Peptide in Biocontrol Fungi Xiaoyan Niu 1, Narit Thaochan 2 and Qiongbo Hu 1,* 1 Key Laboratory of Bio-Pesticide Innovation and Application of Guangdong Province, College of Agriculture, South China Agricultural University, Guangzhou 510642, China; [email protected] 2 Pest Management Biotechnology and Plant Physiology Laboratory, Faculty of Natural Resources, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand; [email protected] * Correspondence: [email protected] Received: 13 March 2020; Accepted: 9 May 2020; Published: 12 May 2020 Abstract: Biocontrol fungi (BFs) play a key role in regulation of pest populations. BFs produce multiple non-ribosomal peptides (NRPs) and other secondary metabolites that interact with pests, plants and microorganisms. NRPs—including linear and cyclic peptides (L-NRPs and C-NRPs)—are small peptides frequently containing special amino acids and other organic acids. They are biosynthesized in fungi through non-ribosomal peptide synthases (NRPSs). Compared with C-NRPs, L-NRPs have simpler structures, with only a linear chain and biosynthesis without cyclization. BFs mainly include entomopathogenic and mycoparasitic fungi, that are used to control insect pests and phytopathogens in fields, respectively. NRPs play an important role of in the interactions of BFs with insects or phytopathogens. On the other hand, the residues of NRPs may contaminate food through BFs activities in the environment. In recent decades, C-NRPs in BFs have been thoroughly reviewed. However, L-NRPs are rarely investigated. In order to better understand the species and potential problems of L-NRPs in BFs, this review lists the L-NRPs from entomopathogenic and mycoparasitic fungi, summarizes their sources, structures, activities and biosynthesis, and details risks and utilization prospects. Keywords: entomopathogenic fungi; mycoparasitic fungi; linear NRPs; diversity 1. Introduction Biocontrol fungi (BFs) play an important role in the control of agricultural and forestry pests. BFs include mainly entomopathogenic and mycoparasitic fungi (EFs and MFs). Entomopathogenic fungi are used extensively in agricultural and medical areas. Beauveria bassiana and Metarhizium anisopliae have been developed as commercial BFs to manage many insect pests worldwide; Cordyceps spp. have been used in traditional medicines in Asia for many years [1,2]. Mycoparasitic fungi such as Trichoderma spp. have been used to control soil-borne plant diseases at commercial scales [3,4]. BFs produce multiple secondary metabolites to interact with pests, plants and microorganisms for better adapting to their environments. Secondary metabolites produced by BFs mainly include polyketides (PKs), terpenes and non-ribosomal peptides (NRPs). NRPs are synthesized by multidomain mega-enzymes named nonribosmal peptide synthetases (NRPSs), without ribosomes and messenger RNAs. NRPSs assemble numerous NRPs with large structural and functional diversity, including more than 20 marketed drugs with antibacterial (penicillin, vancomycin), antitumor (bleomycin) and immunosuppressant (cyclosporine) activities [5]. Apart from the 20 protein amino acids, NRPs also contain rare amino acids and other organic acids. The N-terminal of NPRs are often modified by fatty acids, heterocyclic compounds, glycosylated or phosphorylated structures [6]. NRPs are divided into linear (L-NRPs) J. Fungi 2020, 6, 61; doi:10.3390/jof6020061 www.mdpi.com/journal/jof J. Fungi 2020, 6, x FOR PEER REVIEW 2 of 21 J. Fungi 2020, 6, x FOR PEER REVIEW 2 of 21 fatty acids, heterocyclic compounds, glycosylated or phosphorylated structures [6]. NRPs are J. Fungi 2020, 6, 61 2 of 21 fatty acids, heterocyclicdivided compoundsinto linear (L-NRPs), glycosylat anded cyclic or phosphorylat NRPs（(C-NRPed structuress). Due to lack[6]. ofNRPs cyclization, are L-NRPs have divided into linearpeptide (L-NRPs) chains and cycliccomposed NRPs of（ (Cmultiple-NRPs) . aminoDue to lackacids of often cyclization, modified L-NRP by sdifferent have fat chains or andpept cyclicide chain NRPss composed (C-NRPs).non-protein of Due aminomultiple to lack acids. ofamino L-NRPs cyclization, acids have often L-NRPs antimicrobial, modified have peptide insecticidal,by different chains antiviral composedfat chains or anticancer ofor properties. multiplenon-protein amino amino acidsThere acids often are. L modified- NRPsnumerous have by studies diantimicrobial,fferent and fat reviews chains insecticidal, or on non-protein fungal antiviral non-ribosomal amino or anticancer acids. synthases L-NRPs properties haveand .cyclic peptides [7– antimicrobial,There are numerous insecticidal,9]. studiesHowever, antiviral and little reviews or anticancerattention on fungal has properties. nonbeen-ribosomal paid There to areL-NRPs synthase numerous froms and studiesBFs. cyclic As andpeptides the reviews agricultural [7– and medical on9]. fungalHowever, non-ribosomal littleimportance attention synthases has of BFs,been and it cyclicpaid is necessary to peptides L-NRPs to [ 7 investigatefrom–9]. However, BFs. Asthe the littleBFs agricultural L-NRPs attention source has and been species,medical paid structure, activity toimportance L-NRPs from of BFs, BFs.and it As isbiosynthesis, thenecessary agricultural to as investigate well and as medical their the potential importanceBFs L-NRPs risks. of source BFs, it isspecies necessary, structure, to investigate activity theand BFs biosynthesis L-NRPs source, as well species, as their structure, potential activity risks. and biosynthesis, as well as their potential risks. 2. L-NRPs from Entomopathogenic Fungi 2. L-NRPs from Entomopathogenic Fungi 2. L-NRPs from EntomopathogenicThere are more Fun thangi 1000 species of EFs, mainly belonging to the order Hypocreales. However, There are more than 1000 species of EFs, mainly belonging to the order Hypocreales. However, There are moreonly than seven 1000 L-NRPsspecies ofhave EFs ,been mainly reported belong ingin ato few the orderspecies Hypocreales. of the genera, However, Cordyceps, Paecilomyces, only seven L-NRPs have been reported in a few species of the genera, Cordyceps, Paecilomyces, only seven L-NRPsMetarhizium have been and reported Hirsutella in. a few species of the genera, Cordyceps, Paecilomyces, Metarhizium and Hirsutella. Metarhizium and Hirsutella. 2.1. Cicadapeptins 2.1. Cicadapeptins 2.1. Cicadapeptins Cicadapeptins are obtained from Cordyceps heteropoda ARSEF1880 [10]. There are two analogs of Cicadapeptins are obtained from Cordyceps heteropoda ARSEF1880 [10]. There are two analogs Cicadapeptins arecicadapeptins obtained from with Cordyceps a modified heteropoda N-terminal ARSEF1880 hydroxyproline [10]. There (Hyp) are acylatedtwo analog by n-decanoics of acid and a of cicadapeptins with a modified N-terminal hydroxyproline (Hyp) acylated by n-decanoic acid and cicadapeptins withC-terminal a modified leucine N-terminal (Leu) hydroxyprolinemodified by 1,2-diamino-4-methylpentane (Hyp) acylated by n-decanoic (Figure acid and1). The a two residues of a C-terminal leucine (Leu) modified by 1,2-diamino-4-methylpentane (Figure1). The two residues C-terminal leucineAib (Leu) (alpha-aminoisobutyric modified by 1,2-diamino acid)-4 in-methylpentane the chain lead (Figure to the typical1). The helicaltwo residues structure of of cicadapeptins. of Aib (alpha-aminoisobutyric acid) in the chain lead to the typical helical structure of cicadapeptins. Aib (alpha-aminoisobutyricMoreover, acid)the Hyp in the came chain out lead twice to thein successiontypical helical results structure in the of structural cicadapeptins. change from helical to Moreover, the Hyp came out twice in succession results in the structural change from helical to Moreover, the Hypcontinuously came out twice curved in onesuccession [11]. Cicadapeptins results in the I andstructural II show change inhibitory from effects helical on to Gram-positive and continuously curved one [11]. Cicadapeptins I and II show inhibitory effects on Gram-positive and continuously curvednegati oneve [11]. bacteria Cicadapeptins [11]. I and II show inhibitory effects on Gram-positive and negative bacteria [11]. negative bacteria [11]. Cicadapeptin Composition Cicadapeptin CompositionI nDec- Hyp-Hyp-Val-Aib-Gln-Aib-Leu-X I nDec- Hyp-HypII -Val-AibnDec-Hyp-Hyp-Val-A-Gln-Aib-Leu -X ib-Gln-Aib-Ile-X nDec: n-decanoic acyl； Ile: isoleucine; II nDec-Hyp-Hyp -Val-Aib-Gln-Aib-Ile-X X:1,2-diamino-4-methylpentane; Val: Valine; Gln: nDec: n-decanoic acyl； Ile: isoleucine; glutamine X:1,2-diamino-4-methylpentane; Val: Valine; Gln: glutamine Figure 1. Basic structureFigu andre 1. analogs Basic structure of cicadapeptins and analogs of cicadapeptins Figure 1. Basic structure and analogs of cicadapeptins 2.2. Hirsutellic Acid A 2.2. Hirsutellic Acid A Hirsutellic acid A (Figure2) is a tripeptide isolated from Hirsutella sp. BCC 1528. It has non-polar 2.2. Hirsutellic Acid A Hirsutellic acid A (Figure 2) is a tripeptide isolated from Hirsutella sp. BCC 1528. It has amino acids Ile, Leu and N-methyl-phenylalanine (N-Me-Phe) [12]. Hirsutellic acid A is inhibitory Hirsutellic acidnon-polar A (Figure amino 2) acidsis a tripeptideIle, Leu and isolated N-methyl-phenylalanine from Hirsutella sp. (N-Me-Phe) BCC 1528 .[12]. It has Hirsutellic acid A is against Plasmodium falciparum K1 with an IC50 of 8 µM[12]. non-polar amino acidsinhibitory Ile, Leu against and PlasmodiumN-methyl-phenylalanine falciparum K1 (Nwith-Me an-Phe) IC50 o[1f2 8] .μM Hirsutellic [12]. acid A
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