Table 1.

Realisation of biotechnological approaches for natural product antibiotics from marine fungi, listing all available literature until March 2016. Parameters and fermentation scale were indicated, if available. The origin was stated as concrete as obtained from literature. Abbreviations: Ref., References; EMF, Erlenmeyer flask; STR, stirred tank reactor; MR, Methicillin-Resistant; DSP, Downstream Processing.

Compound, Chemical Class	Producer, Origin	Biotechnological Approach	Antibiotic Activity Against	Ref.
15G265α,β,γ macrocyclic polylactones and lipodepsipeptide	Hypoxylon oceanicum LL‑15G256, mangrove	Optimised medium to increase titres Effect of seawater (negative at low temperature) Transfer to Fernbach flasks and 300-L fermenter	Staphylococcus epidermidis, Xanthomonas campestris Propionibacterium acnes	[38,42]
Ascochytatin, spirodioxynaphthalene	Ascochyta sp. NGB4, floating scrap of festering rope collected at a fishing port	Optimisation of medium at small scale	Bacterial two-component regulatory system	[39]
Ascosetin, tetramic acid	Lindgomycetaceae, Halichondria panicea, (sponge from Baltic Sea)	Transfer from EMF to STR (10 L): adaptation of medium, increase of yield (factor 100) and decrease of cultivation time	S. epidermidis, S. aureus, MR S. aureus, P. acnes, X. campestris, Septoria tritici	[40]
Bis(2-ethylhexyl)phthalate, phthalate *	Cladosporium sp., sea water in mangrove area	Transfer from EMF to STR Record of conditions Scaling (2-L fermenter)	Loktanella hongkongensis, M. luteus, Rhodovulum sp., Ruegeria sp., Pseudoalteromonas piscida, Vibrio harveyi	[41,51]
Calcarides A–E, macrocyclic and linear polyesters	Calcarisporium sp., Wadden sea water	Biosynthesis study for strain characterisation Biological derivatisation For calcaride A: Adaptation of medium in flasks (13‑fold improvement) STR: 200-fold improvement by pH adaptation, C/N ratio, nature of mycelial growth	Macrocyclic compounds: S. epidermidis, X. campestris linear polyesters: no antibiotic activity	[42,52]
Cephalosporin, β-lactam	Aspergillus chrysogenum, sewage water	Full fermentative optimised process, titres up to 25 g/L Semi-synthesis from 7‑aminocephalosporanic acid (enzymatic) Genetic engineering to reduce by‑products Enzymatic treatment in DSP Immobilised cells in a repeated batch tower reactor	Broad spectrum	[43]
	Cephalosporium chrysogenum, sea water	DNA modified by mutagenesis	Broad spectrum	[53]
3-Chloro-2,5-dihydroxy benzyl alcohol, benzene derivative	Ampelomyces sp., marine biofilm	Scaling in EMF	Micrococcus sp., Vibrio sp., Pseudoalteromonas sp., S. aureus, S. haemolyticus	[37]
Chrysogenazine, diketopipera­zine	Penicillium chrysogenum, Porteresia coarctata (mangrove plant, leaves)	Scaling from 1-L to 5-L flasks Yield of the compound enhanced by modifying the carbon and nitrogen source	Vibrio cholera	[44]
Corollosporin and derivates, phthalide derivatives	Corollospora maritima, marine driftwood	Biological derivatives by enzymatic treatment Salt dependency of fermentation	Candida maltosa, Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, S. aureus, S. aureus North German epidemic strain, S. epidermidis, S. haemolyticus	[45,54]
Cyclo-(Pro-Phe), diketopiperazine	Unidentified marine fungus UST030110-009, marine biofilm	Scaling in EMF	Antibacterial antibiofilm: Micrococcus sp., Vibrio sp., Pseudoalteromonas, S. aureus, S. haemolyticus	[37]
Enniatins, cyclodepsipeptides	Halosarpheia sp., mangrove	Heterologous reprogramming of biosynthetic pathways	E. coli, Enterococcus faecium, Salmonella enterica, Shigella dysenteriae, Listeria monocytogenes, Yersinia enterocolitica, Clostridium perfringens, P. aeruginosa, S. aureus	[47]
Exophilin A, 3,5-dihydroxy-decanoic polyester	Exophiala pisciphila, Mycale adhaerens (sponge)	Transfer from EMF to STR (glass bottle fermenter, 20 L)	E. facium, E. faecalis, S. aureus, MR S. aureus	[48]
Lindgomycin, tetramic acid	Lindgomycetaceae, Halichondria panicea (sponge from Baltic Sea)	Adaptation of medium Transfer from EMF to STR (10 L): increase of yield (factor 100) and decrease of cultivation time (from 14 to 7 days)	MR S. aureus, S. epidermidis, P. acnes, X. campestris, S. tritici	[40]
Obioninene, ortho-quinone	Leptosphaeria oraemaris, marine driftwood	Effect of salinity on antibiotic production (in EMF)	Fucus-associated not identified bacterium	[49]
(+)-Terrein, cyclopentenone	Aspergillus terreus PF-26, Phakellia fusca (sponge)	Optimisation of operating factors (5-L STR) such as inoculation, agitation speed, aeration rate, pH control and nutrient feeding	B. subtilis	[55]
Not determined, sesterterpenoid	Fusarium heterosporum and Aspergillus versicolor, driftwood and alga	Metabolic engineering	Broad spectrum	[56]
Not determined	Arthrinium c.f. saccharicola, seawater from a mangrove habitat	Co-culture Stimulation with bacterial elucidators Systematic manipulation of culture conditions: salinity, temperature, pH, and culture medium composition	Pseudoalteromonas spongiae, Vibrio vulnificus	[57]
Not determined	Obligate fungi, marine deep-sea habitats	High pressure cultivation Scaling 20–100 L	Broad spectrum	[58]

* Although bis(2-ethylhexyl)phthalate is a common plasticizer, its total amount was about 20% of the total fungal extract while hardly any plasticware was used during isolation. It was, therefore, assumed that bis(2-ethylhexyl)phthalate was truly produced by the fungus [41].